A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for...Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for TCM modernization has hindered clear guidance for its development.Additionally,cancer remains a significant global public health challenge,largely untreatable with current methods.Therefore,a comprehensive understanding of TCM modernization is crucial for its evolution,revolution,drug discovery,and cancer therapy.This study provides an overview of the history,theory,characteristics,and evolution of TCM,highlighting its potential in cancer prevention and treatment.We propose a definition for TCM modernization,innovative Chinese medicine(ICM),and elucidate strategies to elevate TCM from a supporting role to a leading one.Electronic databases such as PubMed,Web of Science,ScienceDirect,and Clinical Trials were utilized to retrieve relevant literature spanning from 1979 to 2024,with most publications being from the last five years,using keywords like“Traditional Chinese medicine”,“Cancer”,“Mechanism”,and“Clinical trial”.In this study,we introduce the theory of TCM modernization following target identification and initial compound screening:ICM,defined by“3 D”elements:definite active ingredient composition and content,determined functional mechanism,and detection through evidence-based medicine.Overall,the“3 D”definition of ICM will establish a standard for ICM,accelerate TCM modernization,enhance drug discovery targeting cancer and various human diseases,and benefit patients worldwide.展开更多
Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life syste...Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.展开更多
The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small mo...The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small molecule-drug conjugates(SMDCs).SMDCs offer distinct advantages over antibody-drug conjugates(ADCs),including simpler synthesis,lower production costs,and improved solid tumor penetration due to their smaller size.However,challenges remain,such as a limited variety of targeting ligands and the complexity of optimizing selectivity and efficacy within the tumor microenvironment.This review focuses on key aspects such as mechanisms of action,biomarker selection,and the optimization of each component of SMDCs.It also covers SMDCs that have been approved or are currently under active clinical trials,while providing insights into future developments in this promising field of targeted cancer therapies.展开更多
Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors.With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity(CTR-CVT)in...Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors.With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity(CTR-CVT)in tumor patients,noninvasive imaging technologies play pivotal roles in the risk stratification,early diagnosis,monitoring and follow-up for CTR-CVT.In recent years,the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies,with several pertinent guidelines and expert consensus documents issued in China and abroad.However,there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology.Therefore,the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology,the Ultrasound Branch of the Chinese Medical Association,and the Chinese Society of Echocardiography convened experts to formulate the"Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity".Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad,and in conjunction with data derived from evidence-based medical research in China,this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT,aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.展开更多
Anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death.Although the relevant mechanism has not yet been fully elucidated,anastasis is thought to play a role in drug resistance in canc...Anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death.Although the relevant mechanism has not yet been fully elucidated,anastasis is thought to play a role in drug resistance in cancer cells.To date,the regulation of anastasis in normal and cancerous cells has not been clarified.展开更多
Liver cancer is a major killer threatening human health worldwide.At this stage the clinical choice to the treatment of liver cancer is a combination of surgery,chemotherapy and radiotherapy.Alternatively,using hydrog...Liver cancer is a major killer threatening human health worldwide.At this stage the clinical choice to the treatment of liver cancer is a combination of surgery,chemotherapy and radiotherapy.Alternatively,using hydrogen to treat cancer has great prospects and development space.Herein,we fabricated a hierarchical and flexible electrode that being able to continuously generate hydrogen in vivo in the deep abdominal liver through efficient water electrolysis to kill tumor cells and regulate the tumor microenvironment.The flexibility of the electrode facilitated to fit the tumor surface and thus improved the contact area of hydrogen therapy.By in situ growth of molybdenum disulfide on a hierarchical carbon skeleton,improved reaction kinetics and smaller impedance with a low overpotential of 1.02 V at-10 m A/cm^(2)in cell culture medium and Tafel slope of 73 m V/dec were achieved.Animal experiments showed that the electrode could effectively inhibit the growth of human hepatocellular carcinoma cells in nude mice by efficient H_(2)-production in vivo.The apoptosis rate of cancer cells reached 81.8%,and the proliferation rate decreased to 3.39%.Moreover,this treatment does not affect the growth of normal hepatocytes according to the results of cell experiments.This study demonstrated that the in vivo hydrogen production by our flexible electrode is a safe and effective treatment for liver cancer,with the advantages of minimal invasiveness,simple operation,low side effects and low cost.展开更多
Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory ...Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory in integrative oncology,which combines traditional Chinese medicine(TCM)with systems biology to address these limitations.TCM formulas,such as Banxia Xiexin decoction and Qiqin Huchang formula,contain bioactive compounds(e.g.,quercetin and berberine)that modulate interconnected pathways(phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase)and the tumor microenvironment,thereby promoting apoptosis,inhibiting angiogenesis,and regulating immune responses.The theory modernizes TCM’s“Jun-Chen-Zuo-Shi”principle by optimizing herb combinations through network pharmacology and omics technologies.For instance,Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao(Huang Qi)-Curcuma phaeocaulis Val.(E Zhu)pairs co-target hypoxia-inducible factor 1-alpha to suppress metastasis,while artificial intelligence-driven models predict synergistic interactions such as quercetin-cyclin-dependent kinase 1 inhibition.Clinical studies have shown improved outcomes;for instance,modified Banxia Xiexin decoction reduces chemotherapy-induced toxicity in gastric cancer,and Xihuang pill enhances immunotherapy via signal transducer and activator of transcription 3-programmed death-ligand 1 modulation.Despite these advances,challenges remain in standardization and mechanistic validation.Future research should prioritize single-cell sequencing,organoid models,and international collaboration to refine personalized therapies and translate TCM into evidence-based oncology.By integrating empirical knowledge with modern science,molecular compatibility theory provides a robust framework for multitarget drug development and the advancement of integrative cancer therapies.展开更多
Signal transducer and activator of transcription 3(STAT3)is a member of the transcription factors involved in regulating many physiological and pathological processes,such as cell proliferation,angiogenesis and immune...Signal transducer and activator of transcription 3(STAT3)is a member of the transcription factors involved in regulating many physiological and pathological processes,such as cell proliferation,angiogenesis and immune escape.STAT3 has been identified as a potential therapeutic target for various cancers.Although numerous STAT3 inhibitors have been discovered and optimized to directly inhibit STAT3 activity,they are not yet authorized for clinical use and only a few have entered clinical trials.Furthermore,several proteolysis-targeting chimera(PROTAC)molecules with STAT3 degrading effects have been developed.The event-driven action of PROTAC overcome the drawbacks of STAT3,a traditional undruggable target,and addressed possible resistance to small-molecule inhibitors by degrading the entire STAT3 protein.In this review,we presented a brief introduction to STAT3 and its functions in various cancers,and systematically overviewed the pharmacological effects of inhibitors targeting different domains of STAT3 in the last three years,the structural characterization of the main scaffold,the design strategies,and the pharmacological activities of the substituents.Also,the binding patterns and interactions of some inhibitors with STAT3 were analyzed in detail and the recent advances in STAT3 degraders are also summarized.We anticipate that this perspective will contribute to the design and optimize more novel effective and specific STAT3 inhibitors or degraders for carcinoma treatment.展开更多
Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using smal...Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.展开更多
AMP-activated protein kinase(AMPK)is a highly conserved serine/threonine kinase that functions as a central regulator of cellular energy status.In cancer,where metabolic reprogramming enables rapid proliferation and s...AMP-activated protein kinase(AMPK)is a highly conserved serine/threonine kinase that functions as a central regulator of cellular energy status.In cancer,where metabolic reprogramming enables rapid proliferation and survival under stress,AMPK functions as a metabolic checkpoint that restrains tumor growth by inhibiting biosynthetic pathways and promoting catabolic processes,such as autophagy and fatty acid oxidation.Given its role in opposing many hallmarks of cancer metabolism,AMPK has attracted significant interest as a therapeutic target.This review examines the molecular mechanisms by which AMPK influences tumor progression and evaluates the preclinical and clinical evidence for pharmacological AMPK activation using agents such as metformin,phenformin,and canagliflozin.While promising anti-tumor effects have been reported in specific contexts—such as HER2-positive breast cancer,colorectal cancer,and metabolically distinct lung cancer subtypes—clinical efficacy remains variable.Limitations include indirect activation mechanisms,low tissue penetrance,tumor heterogeneity,and lack of reliable biomarkers for patient selection.We discuss emerging strategies to overcome these challenges,including combination therapies,metabolic stratification,and the development of direct AMPK activators or mRNA-based delivery platforms.Together,these insights support a renewed focus on AMPK as a modifiable node in cancermetabolismand a candidate for integration into precision oncology frameworks.展开更多
Toll-like receptors (TLRs) are germ line encoded innate immune sensors that recognize conserved microbial structures and host alarmins, and signal expression of major histocompatibility complex proteins, costimulatory...Toll-like receptors (TLRs) are germ line encoded innate immune sensors that recognize conserved microbial structures and host alarmins, and signal expression of major histocompatibility complex proteins, costimulatory molecules, and inflammatory mediators by macrophages, neutrophils, dendritic cells, and other cell types. These protein receptors are characterized by their ability to respond to invading pathogens promptly by recognizing particular TLR ligands, including flagellin and lipopolysaccharide of bacteria, nucleic acids derived from viruses, and zymosan of fungi. There are 2 major TLR pathways; one is mediated by myeloid differentiation factor 88 (MYD88) adaptor proteins, and the other is independent of MYD88. The MYD88-dependent pathway involves early-phase activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1) and all the TLRs, except TLR3, have been shown to activate this pathway. TLR3 and TLR4 act via MYD88-independent pathways with delayed activation of NF-κB signaling. TLRs play a vital role in activating immune responses. TLRs have been shown to mediate inflammatory responses and maintain epithelial barrier homeostasis, and are highly likely to be involved in the activation of a number of pathways following cancer therapy. Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide. Inflammation is considered a risk factor for many common malignancies including cancers of the colorectum. The key molecules involved in inflammation-driven carcinogenesis include TLRs. As sensors of cell death and tissue remodeling, TLRs may have a universal role in cancer; stimulation of TLRs to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3/4/7/8/9 are all validated targets for cancer therapy, and a number of companies are developing agonists and vaccine adjuvants. On the other hand, antagonists may favor inhibition of signaling responsible for autoimmune responses. In this paper, we review TLR signaling in CRC from carcinogenesis to cancer therapy.展开更多
The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, p...The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.展开更多
Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are current...Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.展开更多
Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lackin...Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.展开更多
Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been som...Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.展开更多
The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials under...The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.展开更多
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
基金supported by the National Natural Science Foundation of China(No.82203343)the National Postdoctoral Program for Innovative Talents of China(No.BX20220273)+3 种基金China Postdoctoral Science Foundation(No.2022M712874)Henan Province Key Research and Development Promotion Special Project(Science and Technology)in 2023(No.232102311007)Henan Province Key Scientific Research Project of Colleges and Universities in 2023(No.23A310007)the Outstanding Youth Project of Henan Provincial Natural Science Foundation(No.252300421123)。
文摘Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for TCM modernization has hindered clear guidance for its development.Additionally,cancer remains a significant global public health challenge,largely untreatable with current methods.Therefore,a comprehensive understanding of TCM modernization is crucial for its evolution,revolution,drug discovery,and cancer therapy.This study provides an overview of the history,theory,characteristics,and evolution of TCM,highlighting its potential in cancer prevention and treatment.We propose a definition for TCM modernization,innovative Chinese medicine(ICM),and elucidate strategies to elevate TCM from a supporting role to a leading one.Electronic databases such as PubMed,Web of Science,ScienceDirect,and Clinical Trials were utilized to retrieve relevant literature spanning from 1979 to 2024,with most publications being from the last five years,using keywords like“Traditional Chinese medicine”,“Cancer”,“Mechanism”,and“Clinical trial”.In this study,we introduce the theory of TCM modernization following target identification and initial compound screening:ICM,defined by“3 D”elements:definite active ingredient composition and content,determined functional mechanism,and detection through evidence-based medicine.Overall,the“3 D”definition of ICM will establish a standard for ICM,accelerate TCM modernization,enhance drug discovery targeting cancer and various human diseases,and benefit patients worldwide.
基金supported by the National Natural Science Foundation of China(Nos.22077044 and 21672080)the Natural Science Foundation of Hubei Province(No.2022CFA033)the funding from Wuhan Institute of Photochemistry and Technology(No.GHY2023KF008).
文摘Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.
基金the financial support from the National Natural Science Foundation of China(Nos.82473781,82173652 and 81872728)the Natural Science Foundation of Jiangsu Province(No.BK20221522)Support from Jiangsu“333 High Level Talents Cultivation”Leading Talents(No.2022–3–16–203)。
文摘The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small molecule-drug conjugates(SMDCs).SMDCs offer distinct advantages over antibody-drug conjugates(ADCs),including simpler synthesis,lower production costs,and improved solid tumor penetration due to their smaller size.However,challenges remain,such as a limited variety of targeting ligands and the complexity of optimizing selectivity and efficacy within the tumor microenvironment.This review focuses on key aspects such as mechanisms of action,biomarker selection,and the optimization of each component of SMDCs.It also covers SMDCs that have been approved or are currently under active clinical trials,while providing insights into future developments in this promising field of targeted cancer therapies.
基金National Key Research and Development Program of China(2022YFC 3602400)Shanghai Municipal Health Commission“Top Priority Research Center”(2023-ZZ02021)+2 种基金Shanghai Public Health Key Discipline Construction Project(GWVI-11.1-26)Shanghai Academic/Technology Research Leader(21XD1432100)Key Research and Development Program of Shandong Province(2021SFGC0503)。
文摘Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors.With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity(CTR-CVT)in tumor patients,noninvasive imaging technologies play pivotal roles in the risk stratification,early diagnosis,monitoring and follow-up for CTR-CVT.In recent years,the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies,with several pertinent guidelines and expert consensus documents issued in China and abroad.However,there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology.Therefore,the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology,the Ultrasound Branch of the Chinese Medical Association,and the Chinese Society of Echocardiography convened experts to formulate the"Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity".Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad,and in conjunction with data derived from evidence-based medical research in China,this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT,aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.
基金supported by the Karadeniz Technical University(Nos.FBA-2018-7951 and FYL-2019-8116)the Scientific and Technological Research Council of Türkiye(TUBITAK)(No.123Z002).
文摘Anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death.Although the relevant mechanism has not yet been fully elucidated,anastasis is thought to play a role in drug resistance in cancer cells.To date,the regulation of anastasis in normal and cancerous cells has not been clarified.
基金financially supported by research grants from the Natural Science Foundation of China(No.52173235)Science and Technology Innovation and Improving Project of Army Medical University(No.2021XJS24)+1 种基金Science and Technology Innovation Capability Enhancement Project of Army Medical University(No.2022XJS20)Key Innovation Project for Clinical Technology of the Second Affiliated Hospital of Army Medical University(No.2018JSLC0025)。
文摘Liver cancer is a major killer threatening human health worldwide.At this stage the clinical choice to the treatment of liver cancer is a combination of surgery,chemotherapy and radiotherapy.Alternatively,using hydrogen to treat cancer has great prospects and development space.Herein,we fabricated a hierarchical and flexible electrode that being able to continuously generate hydrogen in vivo in the deep abdominal liver through efficient water electrolysis to kill tumor cells and regulate the tumor microenvironment.The flexibility of the electrode facilitated to fit the tumor surface and thus improved the contact area of hydrogen therapy.By in situ growth of molybdenum disulfide on a hierarchical carbon skeleton,improved reaction kinetics and smaller impedance with a low overpotential of 1.02 V at-10 m A/cm^(2)in cell culture medium and Tafel slope of 73 m V/dec were achieved.Animal experiments showed that the electrode could effectively inhibit the growth of human hepatocellular carcinoma cells in nude mice by efficient H_(2)-production in vivo.The apoptosis rate of cancer cells reached 81.8%,and the proliferation rate decreased to 3.39%.Moreover,this treatment does not affect the growth of normal hepatocytes according to the results of cell experiments.This study demonstrated that the in vivo hydrogen production by our flexible electrode is a safe and effective treatment for liver cancer,with the advantages of minimal invasiveness,simple operation,low side effects and low cost.
基金supported from the Key R&D Program of Zhejiang(2025C02198)Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Science and Technology Plan Project(GZY-ZJ-KJ-24083).
文摘Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory in integrative oncology,which combines traditional Chinese medicine(TCM)with systems biology to address these limitations.TCM formulas,such as Banxia Xiexin decoction and Qiqin Huchang formula,contain bioactive compounds(e.g.,quercetin and berberine)that modulate interconnected pathways(phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase)and the tumor microenvironment,thereby promoting apoptosis,inhibiting angiogenesis,and regulating immune responses.The theory modernizes TCM’s“Jun-Chen-Zuo-Shi”principle by optimizing herb combinations through network pharmacology and omics technologies.For instance,Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao(Huang Qi)-Curcuma phaeocaulis Val.(E Zhu)pairs co-target hypoxia-inducible factor 1-alpha to suppress metastasis,while artificial intelligence-driven models predict synergistic interactions such as quercetin-cyclin-dependent kinase 1 inhibition.Clinical studies have shown improved outcomes;for instance,modified Banxia Xiexin decoction reduces chemotherapy-induced toxicity in gastric cancer,and Xihuang pill enhances immunotherapy via signal transducer and activator of transcription 3-programmed death-ligand 1 modulation.Despite these advances,challenges remain in standardization and mechanistic validation.Future research should prioritize single-cell sequencing,organoid models,and international collaboration to refine personalized therapies and translate TCM into evidence-based oncology.By integrating empirical knowledge with modern science,molecular compatibility theory provides a robust framework for multitarget drug development and the advancement of integrative cancer therapies.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFA1800403)The Science and Technology Commission of Shanghai Municipality(No.21S11907800)Key Research and Development Program of Ningxia(No.2023BEG02010).
文摘Signal transducer and activator of transcription 3(STAT3)is a member of the transcription factors involved in regulating many physiological and pathological processes,such as cell proliferation,angiogenesis and immune escape.STAT3 has been identified as a potential therapeutic target for various cancers.Although numerous STAT3 inhibitors have been discovered and optimized to directly inhibit STAT3 activity,they are not yet authorized for clinical use and only a few have entered clinical trials.Furthermore,several proteolysis-targeting chimera(PROTAC)molecules with STAT3 degrading effects have been developed.The event-driven action of PROTAC overcome the drawbacks of STAT3,a traditional undruggable target,and addressed possible resistance to small-molecule inhibitors by degrading the entire STAT3 protein.In this review,we presented a brief introduction to STAT3 and its functions in various cancers,and systematically overviewed the pharmacological effects of inhibitors targeting different domains of STAT3 in the last three years,the structural characterization of the main scaffold,the design strategies,and the pharmacological activities of the substituents.Also,the binding patterns and interactions of some inhibitors with STAT3 were analyzed in detail and the recent advances in STAT3 degraders are also summarized.We anticipate that this perspective will contribute to the design and optimize more novel effective and specific STAT3 inhibitors or degraders for carcinoma treatment.
基金supported by National Natural Science Foundation of China(81502688)Cooperation Research Funding of Capital Medical University(2020KJ000514)+1 种基金Cooperation Research Funding of Capital Medical University(2023KJ000814)R&D Program of Beijing Municipal Education Commission(KM202210025024).
文摘Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.
基金supported by the National Research Foundation of Korea(NRF)through the Ministry of Education(2021R1I1A3059820)(to Jea-Hyun Baek).
文摘AMP-activated protein kinase(AMPK)is a highly conserved serine/threonine kinase that functions as a central regulator of cellular energy status.In cancer,where metabolic reprogramming enables rapid proliferation and survival under stress,AMPK functions as a metabolic checkpoint that restrains tumor growth by inhibiting biosynthetic pathways and promoting catabolic processes,such as autophagy and fatty acid oxidation.Given its role in opposing many hallmarks of cancer metabolism,AMPK has attracted significant interest as a therapeutic target.This review examines the molecular mechanisms by which AMPK influences tumor progression and evaluates the preclinical and clinical evidence for pharmacological AMPK activation using agents such as metformin,phenformin,and canagliflozin.While promising anti-tumor effects have been reported in specific contexts—such as HER2-positive breast cancer,colorectal cancer,and metabolically distinct lung cancer subtypes—clinical efficacy remains variable.Limitations include indirect activation mechanisms,low tissue penetrance,tumor heterogeneity,and lack of reliable biomarkers for patient selection.We discuss emerging strategies to overcome these challenges,including combination therapies,metabolic stratification,and the development of direct AMPK activators or mRNA-based delivery platforms.Together,these insights support a renewed focus on AMPK as a modifiable node in cancermetabolismand a candidate for integration into precision oncology frameworks.
基金Supported by grant from United States National Institute of Health(NIH),No.P01 CA87969(to SE Hankinson),No.UM1 CA167552,and No.P01 CA55075(to WC Willett),No.R01 CA137178(to AT Chan),No.P50 CA127003(to CS Fuchs),No.R01 CA151993(to S Ogino)Bennett Family Fund for Targeted Therapies ResearchEntertainment Industry Foundation through National Colorectal Cancer Research Alliance
文摘Toll-like receptors (TLRs) are germ line encoded innate immune sensors that recognize conserved microbial structures and host alarmins, and signal expression of major histocompatibility complex proteins, costimulatory molecules, and inflammatory mediators by macrophages, neutrophils, dendritic cells, and other cell types. These protein receptors are characterized by their ability to respond to invading pathogens promptly by recognizing particular TLR ligands, including flagellin and lipopolysaccharide of bacteria, nucleic acids derived from viruses, and zymosan of fungi. There are 2 major TLR pathways; one is mediated by myeloid differentiation factor 88 (MYD88) adaptor proteins, and the other is independent of MYD88. The MYD88-dependent pathway involves early-phase activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1) and all the TLRs, except TLR3, have been shown to activate this pathway. TLR3 and TLR4 act via MYD88-independent pathways with delayed activation of NF-κB signaling. TLRs play a vital role in activating immune responses. TLRs have been shown to mediate inflammatory responses and maintain epithelial barrier homeostasis, and are highly likely to be involved in the activation of a number of pathways following cancer therapy. Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide. Inflammation is considered a risk factor for many common malignancies including cancers of the colorectum. The key molecules involved in inflammation-driven carcinogenesis include TLRs. As sensors of cell death and tissue remodeling, TLRs may have a universal role in cancer; stimulation of TLRs to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3/4/7/8/9 are all validated targets for cancer therapy, and a number of companies are developing agonists and vaccine adjuvants. On the other hand, antagonists may favor inhibition of signaling responsible for autoimmune responses. In this paper, we review TLR signaling in CRC from carcinogenesis to cancer therapy.
文摘The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.
文摘Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
基金supported by grants from the National Natural Science Foundation of China(Nos.31922042 and 81771966)Science,Technology&Innovation Commission of Shenzhen Municipality(No.JCYJ20160531195129079)。
文摘Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.
文摘Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.
基金Supported by National Natural Science Foundation of China,No.81773656Liaoning Revitalization Talents Program,No.XLYC1808017Shenyang Youth Science and Technology Innovation Talents Program,No.RC190454.
文摘The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.
