To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp...To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(II...To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourc...Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.展开更多
Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitat...Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in...For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.展开更多
Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the si...Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.展开更多
Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanop...Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanoparticles were synthesized by the algal culture and characterized by UV-vis spectroscopy,Fourier transform infrared spectroscopy,field emission scanning electron microscopy and X ray diffraction studies.Antibacterial activity has been studied with free nanoparticles adopting agar diffusion assay,biofilm inhibition assay and nanoparticles fabricated wound dressing against representative Gram-negative organism Pseudomonas aeruginosa and Gram-positive organism Staphylococcus aureus respectively.The in vitro anticancer activity of silver nanoparticles were screened against human Hep2 cell lines by means of MTT assay.Results:Reduction of silver ions by the algal culture was observed during 72 h of incubation and the synthesized nanoparticles were further characterized.Antibacterial study reveals both the strains were susceptible to free nanoparticles and fabricated wound dressing treatment.The in vitro anticancer activity of silver nanoparticles were screened against human Hep 2 cell lines by means of MTT assay which reveals that cell viability has been reduced as dose dependent manner.Conclusions:The observed results imply that silver nanoparticles synthesized from Spirulina platensis cold tolerant strain can be used as potential antibacterial and anticancerous agent.展开更多
Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer p...Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer prevalence and mortality.There is growing interest in discovering dietary patterns and food phytochemicals with potential anticancer effects to support public health strategies.Naturopathy emphasizes cancer prevention primarily through a plant-based diet abundant in functional foods,which enhance the innate defenses of the body against cancer.This article offers an analysis and overview of plant-based functional foods that have demonstrated anticancer properties in scientific studies,focusing on the mechanisms through which phytochemical compounds exert their chemopreventive actions.The plant-based functional foods and their constitution in phytochemicals,scientifically recognized for reducing cancer risk by various actions,are explored—citrus fruit(citrusflavonoids),berries(anthocyanins),pomegranate(ellagic acid),tomato(lycopene),soybeans and soy-based foods(isoflavones),cruciferous vegetables(indole-3-carbinol and sulforaphane),garlic(allicin)and onions(onionin A),green tea(catechins),and turmeric(curcumin).Cancer che-moprevention mechanisms involve antioxidants,anti-inflammatory effects,enhanced detoxification,carcinogen activation block-ade,antiangiogenesis,cell proliferation inhibition,apoptosis,cell cycle arrest,hormone-dependent carcinogenesis suppression,and epigenetic regulation.While numerous studies investigate the health-promoting potential of phytochemicals,it is important to emphasize that cancer prevention is multifactorial,influenced by many factors,such as other lifestyle aspects,genetics,and environment.Future perspectives will concentrate on personalized nutrition and nutrigenomics to enhance cancer prevention strategies,integrating scientific evidence-based naturopathic strategies for more effective cancer prevention.展开更多
Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sis...Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.展开更多
Podophyllotoxin is a well-studied natural product.Because of its unique structure and ability to inhibit cancer cells,it has been changed in different ways to find out its pharmacological properties.This paper discuss...Podophyllotoxin is a well-studied natural product.Because of its unique structure and ability to inhibit cancer cells,it has been changed in different ways to find out its pharmacological properties.This paper discusses the common chemical modifications of podophyllotoxin molecules,including the C-4 and E-4 site replacements.Furthermore,its common inhibitory effects on cancer cells and antiparasitic activities,among others,are outlined by the connection between conformational changes and pharmacological activities.Importantly,Podophyllotoxin can effectively overcome the phenomenon of multidrug resistance through a dual-targeting mechanism,including inhibition of microtubule protein synthesis and topoisomerase II activity,and induces cell cycle arrest and apoptosis.Recent findings reveal its potential to modulate immune responses through the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway,further extending beyond its classical mechanisms.This study finally provides a systematic summary of the activity ofpodophyllotoxin in common cancer cells,including those in the breast,lung,and prostate.展开更多
Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differe...Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.展开更多
Owing to their mechanism of action,antibiotics are prone to inducing drug resistance in the bacteria,viruses,and other pathogens.Therefore,there is an urgent need to develop a novel type of antimicrobial substance to ...Owing to their mechanism of action,antibiotics are prone to inducing drug resistance in the bacteria,viruses,and other pathogens.Therefore,there is an urgent need to develop a novel type of antimicrobial substance to safeguard human health.Antimicrobial peptides,members of the endogenous cathelicidin family in humans,possessing antibacterial,antiviral,and other related activities,represent promising potential alternatives to conventional antibiotics In terms of antibacterial properties.This review summarizes the relevant sources and secondary structure of LL-37 and elucidates that LL-37 not only exerts broad-spectrum antimicrobial effects through non-specific mechanisms such as disrupting pathogen cell membranes,which reduces the likelihood of resistance development,but also exhibits multiple biological activities,including immunomodulation,wound healing promotion,antitumor effects,and alleviation of osteoporosis.Currently,LL-37 shows broad application prospects in fields such as food preservation,pharmaceutical research and development,industrial biomaterial coatings,agricultural and crop disease resistance.However,LL-37 exhibits a dual role,capable of either inhibiting or promoting the proliferation of certain cancer cells depending on the context,which warrants further in-depth investigation using genetic engineering and other approaches.This article summarizes recent research progress on cathelicidin LL-37,outlines its mechanisms of action and application domains,aiming to provide a reference for future research advances on LL-37.展开更多
With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and charact...With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.展开更多
Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibi...Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibitor 3-bromopyruvic acid(3-BrPA)can completely inactivate glycolytic enzymes at extremely low drug concentrations,thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells.Therefore,we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells(HepG2)in vitro;then,we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.Methods In vitro,a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells,and light microscopy confirmed that the HepG2 cells were completely dead.Western blotting was used to detect the expression of key proteins involved in apoptosis.A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment:the control group was perfused with saline in the hepatic artery;the transcatheter arterial embolization(TAE)group was given TAE;and the experimental group was perfused with 3-BrPA combined with TAE.The tumor-bearing rabbits were killed one week after surgery.The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.Results In vitro,the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration.3-BrPA(100μmol/L)could induce the necrosis of HepG2 cells.Stimulation with 50μmol/L 3-BrPA could activate the tumor cell apoptosis pathway.3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.Conclusion 3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.展开更多
Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particu...Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.展开更多
Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic pr...Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic properties were studied.ZAIS QDs showed the brightest photoluminescence and highest quantum yield at an optimized Zn feeding molar ratio of 20%.Those TAPP-grafted nanoparticles(i.e.,ZAIS/PMAO-g-TAPP)were able to produce ^(1)O_(2) in aqueous solution under light irradiation as indicated by the ^(1)O_(2) indicator,9,10-anthracenediyl-bis(methylene)dimalonic acid(ADMA).ZAIS/PMAO-g-TAPP nanoparticles also demonstrate good biocompatibility and low dark toxicity even at a concentration as high as 2.8 mg·mL^(−1),whith can be applied as both a fluorescence probe and a photodynamic therapy(PDT)agent.The PDT treatment showed that the viability of melanoma A2058 cells was less than 10%after treatment with the 420 nm light irradiation for 15 min at a photosensitizer concentration of 1.7 mg·mL^(−1).During the PDT treatment with Escherichia coli,the survival rate of the bacteria decreased by~95%after light irradiation at the same concentration.Such dual-functional ZAIS/PMAO-g-TAPP nanoparticles researched in this study demonstrate promising potential for fluorescence labeling as well as effective PDT treatment against cancer cells and bacteria.展开更多
文摘To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
基金supported by the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003)the National Natural Science Foundation of China(No.22077021).
文摘To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
文摘Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.
文摘Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
基金supported by the Natural Science Foundation of China(No.22077021)the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003).
文摘For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.
文摘Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.
文摘Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanoparticles were synthesized by the algal culture and characterized by UV-vis spectroscopy,Fourier transform infrared spectroscopy,field emission scanning electron microscopy and X ray diffraction studies.Antibacterial activity has been studied with free nanoparticles adopting agar diffusion assay,biofilm inhibition assay and nanoparticles fabricated wound dressing against representative Gram-negative organism Pseudomonas aeruginosa and Gram-positive organism Staphylococcus aureus respectively.The in vitro anticancer activity of silver nanoparticles were screened against human Hep2 cell lines by means of MTT assay.Results:Reduction of silver ions by the algal culture was observed during 72 h of incubation and the synthesized nanoparticles were further characterized.Antibacterial study reveals both the strains were susceptible to free nanoparticles and fabricated wound dressing treatment.The in vitro anticancer activity of silver nanoparticles were screened against human Hep 2 cell lines by means of MTT assay which reveals that cell viability has been reduced as dose dependent manner.Conclusions:The observed results imply that silver nanoparticles synthesized from Spirulina platensis cold tolerant strain can be used as potential antibacterial and anticancerous agent.
文摘Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer prevalence and mortality.There is growing interest in discovering dietary patterns and food phytochemicals with potential anticancer effects to support public health strategies.Naturopathy emphasizes cancer prevention primarily through a plant-based diet abundant in functional foods,which enhance the innate defenses of the body against cancer.This article offers an analysis and overview of plant-based functional foods that have demonstrated anticancer properties in scientific studies,focusing on the mechanisms through which phytochemical compounds exert their chemopreventive actions.The plant-based functional foods and their constitution in phytochemicals,scientifically recognized for reducing cancer risk by various actions,are explored—citrus fruit(citrusflavonoids),berries(anthocyanins),pomegranate(ellagic acid),tomato(lycopene),soybeans and soy-based foods(isoflavones),cruciferous vegetables(indole-3-carbinol and sulforaphane),garlic(allicin)and onions(onionin A),green tea(catechins),and turmeric(curcumin).Cancer che-moprevention mechanisms involve antioxidants,anti-inflammatory effects,enhanced detoxification,carcinogen activation block-ade,antiangiogenesis,cell proliferation inhibition,apoptosis,cell cycle arrest,hormone-dependent carcinogenesis suppression,and epigenetic regulation.While numerous studies investigate the health-promoting potential of phytochemicals,it is important to emphasize that cancer prevention is multifactorial,influenced by many factors,such as other lifestyle aspects,genetics,and environment.Future perspectives will concentrate on personalized nutrition and nutrigenomics to enhance cancer prevention strategies,integrating scientific evidence-based naturopathic strategies for more effective cancer prevention.
基金funded by a grant fromtheMinistero dell’Universita e della Ricerca,PRIN 2022 PNRR grant(Prot.P2022LZXNWto R.B.).
文摘Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.
基金funded by FDCT grants from Macao Science and Technology University to PC(Project Code:0005-2023-RIA1)。
文摘Podophyllotoxin is a well-studied natural product.Because of its unique structure and ability to inhibit cancer cells,it has been changed in different ways to find out its pharmacological properties.This paper discusses the common chemical modifications of podophyllotoxin molecules,including the C-4 and E-4 site replacements.Furthermore,its common inhibitory effects on cancer cells and antiparasitic activities,among others,are outlined by the connection between conformational changes and pharmacological activities.Importantly,Podophyllotoxin can effectively overcome the phenomenon of multidrug resistance through a dual-targeting mechanism,including inhibition of microtubule protein synthesis and topoisomerase II activity,and induces cell cycle arrest and apoptosis.Recent findings reveal its potential to modulate immune responses through the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway,further extending beyond its classical mechanisms.This study finally provides a systematic summary of the activity ofpodophyllotoxin in common cancer cells,including those in the breast,lung,and prostate.
基金supported by the National Natural Science Foundation of China,(Nos.82272151,82204318)Liaoning Revitalization Talents Program(No.XLYC2203083)+2 种基金Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220389)Postdoctoral Fellowship Program of CPSF(No.GZC20231732)China Postdoctoral Science Foundation(Nos.2023TQ0222,2023MD744229).
文摘Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
基金support provided by Tianjin University of Science and Technology 2023 College Students’Innovation and Entrepreneurship Training Program Project“Novel Antibiotic-The Role of Antimicrobial Peptide VIP in Poultry Farming”No.:202310057068.
文摘Owing to their mechanism of action,antibiotics are prone to inducing drug resistance in the bacteria,viruses,and other pathogens.Therefore,there is an urgent need to develop a novel type of antimicrobial substance to safeguard human health.Antimicrobial peptides,members of the endogenous cathelicidin family in humans,possessing antibacterial,antiviral,and other related activities,represent promising potential alternatives to conventional antibiotics In terms of antibacterial properties.This review summarizes the relevant sources and secondary structure of LL-37 and elucidates that LL-37 not only exerts broad-spectrum antimicrobial effects through non-specific mechanisms such as disrupting pathogen cell membranes,which reduces the likelihood of resistance development,but also exhibits multiple biological activities,including immunomodulation,wound healing promotion,antitumor effects,and alleviation of osteoporosis.Currently,LL-37 shows broad application prospects in fields such as food preservation,pharmaceutical research and development,industrial biomaterial coatings,agricultural and crop disease resistance.However,LL-37 exhibits a dual role,capable of either inhibiting or promoting the proliferation of certain cancer cells depending on the context,which warrants further in-depth investigation using genetic engineering and other approaches.This article summarizes recent research progress on cathelicidin LL-37,outlines its mechanisms of action and application domains,aiming to provide a reference for future research advances on LL-37.
文摘With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.
基金National Natural Science Foundation of China(No.82202281)for the funding support,and Yu-miao Wei for his review of the manuscript.
文摘Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibitor 3-bromopyruvic acid(3-BrPA)can completely inactivate glycolytic enzymes at extremely low drug concentrations,thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells.Therefore,we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells(HepG2)in vitro;then,we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.Methods In vitro,a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells,and light microscopy confirmed that the HepG2 cells were completely dead.Western blotting was used to detect the expression of key proteins involved in apoptosis.A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment:the control group was perfused with saline in the hepatic artery;the transcatheter arterial embolization(TAE)group was given TAE;and the experimental group was perfused with 3-BrPA combined with TAE.The tumor-bearing rabbits were killed one week after surgery.The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.Results In vitro,the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration.3-BrPA(100μmol/L)could induce the necrosis of HepG2 cells.Stimulation with 50μmol/L 3-BrPA could activate the tumor cell apoptosis pathway.3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.Conclusion 3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.
文摘Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.
基金supported by the Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions(TAPP)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the CZ-EdU Joint Laboratory on Biomedical Materials(CZ20190019).
文摘Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic properties were studied.ZAIS QDs showed the brightest photoluminescence and highest quantum yield at an optimized Zn feeding molar ratio of 20%.Those TAPP-grafted nanoparticles(i.e.,ZAIS/PMAO-g-TAPP)were able to produce ^(1)O_(2) in aqueous solution under light irradiation as indicated by the ^(1)O_(2) indicator,9,10-anthracenediyl-bis(methylene)dimalonic acid(ADMA).ZAIS/PMAO-g-TAPP nanoparticles also demonstrate good biocompatibility and low dark toxicity even at a concentration as high as 2.8 mg·mL^(−1),whith can be applied as both a fluorescence probe and a photodynamic therapy(PDT)agent.The PDT treatment showed that the viability of melanoma A2058 cells was less than 10%after treatment with the 420 nm light irradiation for 15 min at a photosensitizer concentration of 1.7 mg·mL^(−1).During the PDT treatment with Escherichia coli,the survival rate of the bacteria decreased by~95%after light irradiation at the same concentration.Such dual-functional ZAIS/PMAO-g-TAPP nanoparticles researched in this study demonstrate promising potential for fluorescence labeling as well as effective PDT treatment against cancer cells and bacteria.
