Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revita...Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revitalizes the tumor immune microenvironment(TIME)in OSCC by integrating upconversion-based photodynamic therapy(PDT)with chemotherapy.Using a red blood cell membraneinspired biomimetic nanoplatform,our approach concurrently delivers chlorin e6@upconversion nanoparticles(Ce6@UCNP)and doxorubicin(DOX).By leveraging fluorescence resonance energy transfer(FRET)for 980 nm to 660 nm upconversion excitation,we address challenges such as limited tissue penetration and tissue damage,as well as nanoplatform issues including immunogenicity and targeting inaccuracy Our integrated approach enhances PDT and chemotherapy with the goal of transforming immunologically“cold”tumors into“hot”ones through a cascaded therapy,thereby revitalizing the tumor immune microenvironment in OSCC.展开更多
Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of d...Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.展开更多
Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia a...Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors.This study propose d a novel tumor treatment approach,focusing on ROS-mediated therapy by targ eting the nucleus and depleting glutathione(GSH)levels,which was achieved through a nanoplatform(Pt^(2+)-CDs@PpIX)with integrated functions including GSH detection and depletion,pH-responsive drug release,and nuclear targeting.The Pt^(2+)-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility.Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT,as demonstrated in vitro using Pt^(2+)-CDs@PpIX,which also exhibited significant cellular uptake.Pt^(2+)-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tum or microenvironment models(3 DM-7721).Moreover,in 3 DM-7721 models,hepatoma cells(SMMC-7721)demonstrated significant inhibition of motility,invasion,and colony formation after exposure to Pt^(2+)-CDs@PpIX.Furthermore,intravenous administration of the Pt^(2+)-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting,followed by ultrasound-triggered therapy,without adverse effects in nude mice.Hence,this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs.展开更多
How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indo...How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indocyanine green （ICG） in ZlF-8 nanoparticles （NPs）. The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading chemotherapy agent hydrophobic doxorubicin （DOX）, ICG@ZIF-8-DOX NPs exhibit the chem-and photothermal synergistic therapy for tumor. In addition, it is found that the embedded ICG molecules in ICG@ZlF-8 NPs can be disassociated and released into the solution upon the 808 nm laser irradiation, demonstrating that as-prepared ICG@ZIF-8 NPs can also be used as the optical imaging probe to trace the degradability behavior of resulting NPs in future展开更多
Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and...Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.展开更多
One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in tumors.Tumor cells generally display the higher oxidative level than normal cells,and also displayed...One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in tumors.Tumor cells generally display the higher oxidative level than normal cells,and also displayed the heterogeneity in terms of redox homeostasis level.We previously found that the disulfide bond-linkage demonstrates surprising oxidationsensitivity to form the hydrophilic sulfoxide and sulphone groups.Herein,we develop oxidation-strengthened prodrug nanosystem loaded with pyropheophorbide a(PPa)to achieve light-activatable cascade drug release and enhance therapeutic efficacy.The disulfide bond-driven prodrug nanosystems not only respond to the redox-heterogeneity in tumor,but also respond to the exogenous oxidant(singlet oxygen)elicited by photosensitizers.Once the prodrug nanoparticles(NPs)are activated under irradiation,they would undergo an oxidative self-strengthened process,resulting in a facilitated drug cascade release.The IC50 value of the PPa@PTX-S-S NPs without irradiation was 2-fold higher than those of NPs plus irradiation.In vivo,the PPa@PTX prodrug NPs display prolonged systemic circulation and increased accumulation in tumor site.The PPa@PTXS-S NPs showed much higher efficiency than free PTX or the PPa@PTX-C-C NPs to suppress the growth of 4 T1 tumors.Therefore,this novel oxidation-strengthened disulfide-bridged prodrug-nanosystem has a great potential in the enhanced efficacy of cancer synergetic photochemotherapy.展开更多
Sepsis,a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection,is a leading contributor to mortality in intensive care units.Sepsis-related deaths have been reported to accou...Sepsis,a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection,is a leading contributor to mortality in intensive care units.Sepsis-related deaths have been reported to account for 19.7%of all global deaths.However,no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis.Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis.Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry,targeting infection and/or imbalanced immune responses,have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment.Nanoplatforms can overcome the barriers faced by clinical strategies,including delayed diagnosis,drug resistance and incapacity to manage immune disorders.Here,we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts,summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies.Based on these state-of-the-art studies,this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.展开更多
To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modi...To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared,denoted SMONs-HA-Cy5.5,and comparative studies between SMONs-HA-Cy5.5(24.2 MPa)and stiff counterparts(79.2 MPa)are conducted.Results indicate that,apart from exhibiting a twofold increase in tumor cellular uptake,the soft nanoplatforms also display a remarkable pharmacokinetic advantage,resulting in considerably improved tumor accumulation.Moreover,SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration,achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts.Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels,diffuse farther in the dense extracellular matrix,and reach deeper tumor tissues compared to the stiff ones.Specifically,the soft nanoplatforms generate a 16-fold improvement(43 vs.2.72μm)in diffusion distance in tumor parenchyma.Based on the significantly improved blood circulation and tumor accumulation/penetration,a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5.The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.展开更多
Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focus...Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.展开更多
Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the...Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.展开更多
Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent...Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.展开更多
Immunotherapy acts as an essential modality in modulating a broad variety of immune responses to cure diseases and has been regarded as a powerful therapeutic strategy in cancer treatment in the past decades.However,t...Immunotherapy acts as an essential modality in modulating a broad variety of immune responses to cure diseases and has been regarded as a powerful therapeutic strategy in cancer treatment in the past decades.However,the application of immunotherapeutic agents is limited by their low tumor targeting capability,poor tumor penetration ability,and potential immune-related adverse events in physiological environments.Engineered liposomal nanoplatforms can help to reduce immune-related side effects,precisely deliver the drugs to the tumor site,and enhance the treatment power of immunotherapeutic agents by restricting them within the cavities of the liposomes and modifying the liposomes with targeting components and biocompatible materials to reduce their burst release,unwanted dispersion,and blood clearance.This review discusses the recent progress in the development of liposome-assisted immunotherapy for treating various cancers,including the design of liposomal nanoplatforms,the features of different immunotherapy modalities,and the strategies for activating immune responses.In addition,this review also introduces the strategies for strengthening liposome-based immunotherapy by optimizing liposomal design,exploring the pairing of different drugs,and combining with different therapeutic modalities.Finally,this review proposes some current limitations and future research directions for liposomal nanoplatform-assisted cancer immunotherapy.展开更多
Modern oncology is rapidly evolving,driven by recent advances in RNA-based therapeutics.As new emerging cutting-edge technology,mRNA vaccines hold excellent promise for encoding immunostimulatory molecules,tumor-assoc...Modern oncology is rapidly evolving,driven by recent advances in RNA-based therapeutics.As new emerging cutting-edge technology,mRNA vaccines hold excellent promise for encoding immunostimulatory molecules,tumor-associated antigens,neoantigens,and chimeric antigen receptors for T-cell reprogramming.RNA interference tools enable highly effective post-transcriptional gene silencing that has rapidly progressed towards more tailored antitumor treatments targeting key molecular players in tumor progression and drug resistance.The inherent challenges and limitations of RNA-based tools,such as size,low stability and surface charges hindering direct cell entry,along with the short circulatory half-life and rapid clearance,call for new and improved RNA delivery systems enabling enhanced gene delivery.Nanoplatforms,particularly certain types of lipid,polymeric nanoparticles and inorganic nanoparticles,provide designed means to address the challenges of RNA delivery and cellular uptake.This paper explores the challenges and barriers while giving insight into the future perspective of RNA-based cancer therapeutics in the context of delivery nanoplatforms and the challenges during development.展开更多
A dual-functional nanoplatform is demonstrated that is found to have the characteristics of cancer cell targeting,pH response,near-infrared fluorescence imaging,and lysosome targeting.It can simultaneously achieve pyr...A dual-functional nanoplatform is demonstrated that is found to have the characteristics of cancer cell targeting,pH response,near-infrared fluorescence imaging,and lysosome targeting.It can simultaneously achieve pyroptosis and ferroptosis under the mediation of photons for cancer immunotherapy.展开更多
Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overe...Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.展开更多
Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and trea...Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer.Herein,we reported a novel super-paramagnetic iron oxide(SPIO)based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose.This polyethylene glycol with four phenylboronic acid(PEG-B4)/CNTs@porphyrin(ph)/SPIO(BCPS)nanoplatform was simply prepared via integrated SPIO,ph,and a novel dendrimer with PEG liner and four PBA groups(PEG-B4)on the surface of carbon nanotubes(CNTs).Subsequently,a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering.Moreover,the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy.Furthermore,the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4.We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor(1 mm)in the liver,but also effectively ablate tumors in a xenograft model,thereby achieving a complete cure rate of 100%at low laser dose.Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.展开更多
Photothermal therapy has the characteristics of minimal invasiveness,controllability,high efficiency,and strong specificity,which can effectively make up for the toxic side effects and tumor resistance caused by tradi...Photothermal therapy has the characteristics of minimal invasiveness,controllability,high efficiency,and strong specificity,which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment.However,due to the limited tissue penetration of infrared light,it is difficult to promote and apply in clinical practice.The eye is the only transparent tissue in human,and infrared light can easily penetrate the eye tissue,so it is expected that photothermal therapy can be used to treat fundus diseases.Here in,a new nano-platform assembled by liposome and indocyanine green(ICG) was used to treat retinoblastoma.ICG was assembled in liposomes to overcome some problems of ICG itself.For example,ICG is easily quenched,self-aggregating and instability.Moreover,liposomes can prevent free ICG from being cleared through the systemic circulation.The construction of the nano-platform not only ensured the stability of ICG in vivo,but also realized imaging-guide photothermal therapy,which created a new strategy for the treatment of retinoblastoma.展开更多
The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the ...The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.展开更多
Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(R...Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.展开更多
CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently t...CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.展开更多
基金supported by the National Natural Science Foundation of China(No.81802709)the Shandong Provincial Natural Science Foundation,China(Nos.ZR2023MH230,ZR2023MH096)+1 种基金the Shandong Provincial Postdoctoral Innovative Talents Funded SchemePlan of Young Scholars of Shandong University。
文摘Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revitalizes the tumor immune microenvironment(TIME)in OSCC by integrating upconversion-based photodynamic therapy(PDT)with chemotherapy.Using a red blood cell membraneinspired biomimetic nanoplatform,our approach concurrently delivers chlorin e6@upconversion nanoparticles(Ce6@UCNP)and doxorubicin(DOX).By leveraging fluorescence resonance energy transfer(FRET)for 980 nm to 660 nm upconversion excitation,we address challenges such as limited tissue penetration and tissue damage,as well as nanoplatform issues including immunogenicity and targeting inaccuracy Our integrated approach enhances PDT and chemotherapy with the goal of transforming immunologically“cold”tumors into“hot”ones through a cascaded therapy,thereby revitalizing the tumor immune microenvironment in OSCC.
基金National Key Research and Development Program of China(No.2022YFD2200602)111 Project(No.B20088)+1 种基金National Natural Science Foundation of China(Nos.52202345 and 31930076)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)。
文摘Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.
基金supported by the National Natural Science Foundation of China(No.62031022)the Sha nxi Provincial Basic Research Project(Nos.202103021221006 and 20210302123040)+2 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Key R&D Program of Shanxi Province(No.202302130501006)the Shanxi‒Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors.This study propose d a novel tumor treatment approach,focusing on ROS-mediated therapy by targ eting the nucleus and depleting glutathione(GSH)levels,which was achieved through a nanoplatform(Pt^(2+)-CDs@PpIX)with integrated functions including GSH detection and depletion,pH-responsive drug release,and nuclear targeting.The Pt^(2+)-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility.Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT,as demonstrated in vitro using Pt^(2+)-CDs@PpIX,which also exhibited significant cellular uptake.Pt^(2+)-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tum or microenvironment models(3 DM-7721).Moreover,in 3 DM-7721 models,hepatoma cells(SMMC-7721)demonstrated significant inhibition of motility,invasion,and colony formation after exposure to Pt^(2+)-CDs@PpIX.Furthermore,intravenous administration of the Pt^(2+)-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting,followed by ultrasound-triggered therapy,without adverse effects in nude mice.Hence,this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs.
基金financially supported by the State Key Basic Research Program of the PRC(No.2014CB744501)the NSF of China(No.81771976)+1 种基金Fundamental Research Funds for the Central Universitiesthe joint fund of Southeast University and Nanjing Medical University
文摘How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indocyanine green （ICG） in ZlF-8 nanoparticles （NPs）. The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading chemotherapy agent hydrophobic doxorubicin （DOX）, ICG@ZIF-8-DOX NPs exhibit the chem-and photothermal synergistic therapy for tumor. In addition, it is found that the embedded ICG molecules in ICG@ZlF-8 NPs can be disassociated and released into the solution upon the 808 nm laser irradiation, demonstrating that as-prepared ICG@ZIF-8 NPs can also be used as the optical imaging probe to trace the degradability behavior of resulting NPs in future
基金Financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51803006,51673190,51603204,51673187,and 51520105004)the Science and Technology Development Program of Jilin Province(Grant Nos.20190201068JC,20170101102JC,and 20160414047GH)+2 种基金the Medical and Health Program of Jilin Province(Grant No.20190304047YY)the Youth Talents Promotion Project of Jilin Province(Grant No.181909)and the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019005).
文摘Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.
基金financially supported by National Nature Science Foundation of China(No.81872816,81703451)Liaoning Revitalization Talents Program,No XLYC1808017+2 种基金Key projects of Technology bureau in Shenyang,No18400408Key projects of Liaoning Province Department of Education,No.2017LZD03supported by Heilongjiang Provincial Key Laboratory of Plant Genetic Engineering and Biological Fermentation Engineering for Cold Region。
文摘One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in tumors.Tumor cells generally display the higher oxidative level than normal cells,and also displayed the heterogeneity in terms of redox homeostasis level.We previously found that the disulfide bond-linkage demonstrates surprising oxidationsensitivity to form the hydrophilic sulfoxide and sulphone groups.Herein,we develop oxidation-strengthened prodrug nanosystem loaded with pyropheophorbide a(PPa)to achieve light-activatable cascade drug release and enhance therapeutic efficacy.The disulfide bond-driven prodrug nanosystems not only respond to the redox-heterogeneity in tumor,but also respond to the exogenous oxidant(singlet oxygen)elicited by photosensitizers.Once the prodrug nanoparticles(NPs)are activated under irradiation,they would undergo an oxidative self-strengthened process,resulting in a facilitated drug cascade release.The IC50 value of the PPa@PTX-S-S NPs without irradiation was 2-fold higher than those of NPs plus irradiation.In vivo,the PPa@PTX prodrug NPs display prolonged systemic circulation and increased accumulation in tumor site.The PPa@PTXS-S NPs showed much higher efficiency than free PTX or the PPa@PTX-C-C NPs to suppress the growth of 4 T1 tumors.Therefore,this novel oxidation-strengthened disulfide-bridged prodrug-nanosystem has a great potential in the enhanced efficacy of cancer synergetic photochemotherapy.
基金the National Key Research and Development Program of China(Grant No.2018YFC2001904).
文摘Sepsis,a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection,is a leading contributor to mortality in intensive care units.Sepsis-related deaths have been reported to account for 19.7%of all global deaths.However,no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis.Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis.Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry,targeting infection and/or imbalanced immune responses,have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment.Nanoplatforms can overcome the barriers faced by clinical strategies,including delayed diagnosis,drug resistance and incapacity to manage immune disorders.Here,we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts,summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies.Based on these state-of-the-art studies,this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.
基金supported by National Key Basic Research Program of China(973 Program),China(2014CB744504)the National Natural Science Foundation of China,China(81971675,21603106 and 81971681)the Natural Science Foundation of Jiangsu Province,China(BK20160017)。
文摘To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared,denoted SMONs-HA-Cy5.5,and comparative studies between SMONs-HA-Cy5.5(24.2 MPa)and stiff counterparts(79.2 MPa)are conducted.Results indicate that,apart from exhibiting a twofold increase in tumor cellular uptake,the soft nanoplatforms also display a remarkable pharmacokinetic advantage,resulting in considerably improved tumor accumulation.Moreover,SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration,achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts.Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels,diffuse farther in the dense extracellular matrix,and reach deeper tumor tissues compared to the stiff ones.Specifically,the soft nanoplatforms generate a 16-fold improvement(43 vs.2.72μm)in diffusion distance in tumor parenchyma.Based on the significantly improved blood circulation and tumor accumulation/penetration,a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5.The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.
基金supported by the Guangdong Nature Resource Center(No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498 and 2019A1515011619)+2 种基金Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120063)National Natural Science Foundation of China(No.81803877)supported by the China Postdoctoral Science Foundation(No.2022M721535)。
文摘Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.
基金supported by the National Natural Science Foundation of China(Nos.82302373,81903846)Natural Science Foundation of Sichuan Province(No.2022NSFSC1925)+1 种基金Chengdu Technology Innovation Research and Development Project(No.2022-YF05-01546-SN)the Introduction of Talents Research Project of Chengdu University(No.2081921049)。
文摘Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.
基金supported by the Open Research Fund of Southeast University and Jiangsu Province Hospital(2024-M01)the National Natural Science Foundation of China(82372127)+1 种基金the Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(GKE-KF202305)the Fundamental Research Funds for the Central Universities(2242023K5007)。
文摘Immunotherapy acts as an essential modality in modulating a broad variety of immune responses to cure diseases and has been regarded as a powerful therapeutic strategy in cancer treatment in the past decades.However,the application of immunotherapeutic agents is limited by their low tumor targeting capability,poor tumor penetration ability,and potential immune-related adverse events in physiological environments.Engineered liposomal nanoplatforms can help to reduce immune-related side effects,precisely deliver the drugs to the tumor site,and enhance the treatment power of immunotherapeutic agents by restricting them within the cavities of the liposomes and modifying the liposomes with targeting components and biocompatible materials to reduce their burst release,unwanted dispersion,and blood clearance.This review discusses the recent progress in the development of liposome-assisted immunotherapy for treating various cancers,including the design of liposomal nanoplatforms,the features of different immunotherapy modalities,and the strategies for activating immune responses.In addition,this review also introduces the strategies for strengthening liposome-based immunotherapy by optimizing liposomal design,exploring the pairing of different drugs,and combining with different therapeutic modalities.Finally,this review proposes some current limitations and future research directions for liposomal nanoplatform-assisted cancer immunotherapy.
基金support from the Australian Research Council Future Fellowship(No.FT180100361,Australia)Discovery Project(No.DP230100556,Australia)support from Australian Laureate Fellowship(FL230100023,Australia).
文摘Modern oncology is rapidly evolving,driven by recent advances in RNA-based therapeutics.As new emerging cutting-edge technology,mRNA vaccines hold excellent promise for encoding immunostimulatory molecules,tumor-associated antigens,neoantigens,and chimeric antigen receptors for T-cell reprogramming.RNA interference tools enable highly effective post-transcriptional gene silencing that has rapidly progressed towards more tailored antitumor treatments targeting key molecular players in tumor progression and drug resistance.The inherent challenges and limitations of RNA-based tools,such as size,low stability and surface charges hindering direct cell entry,along with the short circulatory half-life and rapid clearance,call for new and improved RNA delivery systems enabling enhanced gene delivery.Nanoplatforms,particularly certain types of lipid,polymeric nanoparticles and inorganic nanoparticles,provide designed means to address the challenges of RNA delivery and cellular uptake.This paper explores the challenges and barriers while giving insight into the future perspective of RNA-based cancer therapeutics in the context of delivery nanoplatforms and the challenges during development.
文摘A dual-functional nanoplatform is demonstrated that is found to have the characteristics of cancer cell targeting,pH response,near-infrared fluorescence imaging,and lysosome targeting.It can simultaneously achieve pyroptosis and ferroptosis under the mediation of photons for cancer immunotherapy.
基金supported by the National Basic Research Program of China(No.81573371)the Key Projects of Liaoning Province Department of Education(No.2017LZD03,China)
文摘Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.
基金This work was supported by National Natural Science Foundation of China(No.81971664)Shanghai Pujang Program(2019PJD044)+1 种基金National Key Research and Development Project of China(2016YFB0303200)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support.
文摘Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer.Herein,we reported a novel super-paramagnetic iron oxide(SPIO)based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose.This polyethylene glycol with four phenylboronic acid(PEG-B4)/CNTs@porphyrin(ph)/SPIO(BCPS)nanoplatform was simply prepared via integrated SPIO,ph,and a novel dendrimer with PEG liner and four PBA groups(PEG-B4)on the surface of carbon nanotubes(CNTs).Subsequently,a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering.Moreover,the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy.Furthermore,the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4.We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor(1 mm)in the liver,but also effectively ablate tumors in a xenograft model,thereby achieving a complete cure rate of 100%at low laser dose.Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.
基金financially supported by National Natural Science Foundation of China(7212092,81770887)China Postdoctoral Science Foundation(2019M650558)+1 种基金Beijing Postdoctoral Research FoundationBeijing Chaoyang District Postdoctoral Research Foundation。
文摘Photothermal therapy has the characteristics of minimal invasiveness,controllability,high efficiency,and strong specificity,which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment.However,due to the limited tissue penetration of infrared light,it is difficult to promote and apply in clinical practice.The eye is the only transparent tissue in human,and infrared light can easily penetrate the eye tissue,so it is expected that photothermal therapy can be used to treat fundus diseases.Here in,a new nano-platform assembled by liposome and indocyanine green(ICG) was used to treat retinoblastoma.ICG was assembled in liposomes to overcome some problems of ICG itself.For example,ICG is easily quenched,self-aggregating and instability.Moreover,liposomes can prevent free ICG from being cleared through the systemic circulation.The construction of the nano-platform not only ensured the stability of ICG in vivo,but also realized imaging-guide photothermal therapy,which created a new strategy for the treatment of retinoblastoma.
基金supported by National Natural Science Foundation of China (No.32201128,No.82270262,and No.82070408)Zhejiang TCM Science and Technology Program TCM modernization Special project,China (No.2022ZX012).
文摘The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.
基金NSFC,Grant/Award Numbers:52073045,51773195Key Scientific and Technological Project of Jilin Province,Grant/Award Number:20190701010GH+2 种基金Development and Reform Commission of Jilin Province,Grant/Award Number:2020C035-5Changchun Science and Technology Bureau,Grant/Award Number:21ZGY19EPSRC,Grant/Award Number:EP/L02621X/1。
文摘Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.
基金The authors acknowledge the financial support from National Natural Science Foundation of China(Grant Nos.51773198,51673188,and 21975246)The animal study protocol was approved by the Institutional Animal Care and Use Committee at Chinese Academy of Sciences.
文摘CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.
