Au-Ft,as a green synthesized nanoparticle,is composed of a ferritin nanocage enclosing a pair of Au nanoclusters inside.Our previous study has demonstrated that Au-Ft can be an excellentfluorescent probe for whole bod...Au-Ft,as a green synthesized nanoparticle,is composed of a ferritin nanocage enclosing a pair of Au nanoclusters inside.Our previous study has demonstrated that Au-Ft can be an excellentfluorescent probe for whole body imaging of mice with kidney specific targeting.But,the accuratelocalization of Au-Ft in kidney is still absent.In the current study,we detected and assessed the cellular and subcellular localization of Au-Ft in renal cortex and medulla of nu/nu mice after tailvein injection by using Nuance optical system(CRi,Woburn,USA)and inForm intelligent image analysis soft ware based on single cell segmentation.We obtained the fluorescence intensity and cellular location of kidney-targeting Au-Ft probe in particular cell of renal glomerulus or renaltubules,which provided valuable proofs to clarify the mechanism of Au-Ft selective enrichment in kidney and the associated metabolic processes.展开更多
As a representative chemotherapeutic drug,docetaxel(DTX)has been used for breast cancer treatment for decades.However,the poor solubility of DTX limits its efficacy,and the DTX based therapy increases the metastasis r...As a representative chemotherapeutic drug,docetaxel(DTX)has been used for breast cancer treatment for decades.However,the poor solubility of DTX limits its efficacy,and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4(CXCR4)expression during the treatment.Herein,we conjugated CXCR4 antagonist peptide(CTCE)with DTX(termed CTCE-DTX)as an anti-metastasis agent to treat breast cancer.CTCE-DTX could selfassemble to nanoparticles,targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy.Thus,the CTCE-DTX NPs achieved promising efficacy on inhibiting both bonespecific metastasis and lung metastasis of triple-negative breast cancer.Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.展开更多
Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously el...Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of GrB.To circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer chemo-immunotherapy.In vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ICD.Meanwhile,D3RL can competitively relieve the inhibition of Sb9 to GrB.The restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor effect.Taken together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.展开更多
Interfacial assembly has been intensively investigated in fabricating biomaterials and nanodevices for various applications.Recently,due to the precise sequence programmability,unique molecular recognition ability,and...Interfacial assembly has been intensively investigated in fabricating biomaterials and nanodevices for various applications.Recently,due to the precise sequence programmability,unique molecular recognition ability,and good biocompatibility,deoxyribonucleic acid(DNA)has been explored as superior building blocks to assemble at bio-interface for manipulating biological entities.To the best of our knowledge,the advances in this area have not been systematically summarized.To provide an overview of the area,in this review,the recently developed DNA assembly strategies on bio-interfaces were well summarized,and their representative works are exampled to illustrate how to rationally and elaborately design DNA molecules to realize functional integration and emerging of novel biological functionalities with high controllability and programmability.Furthermore,the biomedical applications of DNA assembly at bio-interface are categorially elaborated.The fascinating and unique advantages of DNA assembly systems are fully discussed in the exemplified applications to show the distinguished perspective of DNA in the future development.At the end of this review,the current limitations and challenges in applications and potential improvement strategies for DNA assembly at bio-interface are fully discussed.The future development direction is deliberated.We envision that this review will help scientists in the interdisciplinary fields gain a more comprehensive understanding of the DNA assembly at bio-interface,and therefore jointly promote the advances in this field.展开更多
Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly...Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic HCC.HSCs play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver fibrosis.CAFs can be derived from activated HSCs and differentiate into ECM-producing myofibroblasts.Moreover,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune response.Combined therapeutic strategies show reduced drug resistance and side effects.Nanotechnology-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple mechanisms.In this review,we will discuss recent developments in combinational strategies based on nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC treatment.We will also identify the major challenges that the field is facing and offer some insights for future drug discovery.展开更多
Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and ima...Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated na-ture of cancer.With rationally designed multifunctionality and programmable assembly of functional subunits,the in vivo behaviors of intelligent nanosystems have become increasingly tunable,making them more efficient in performing sophisticated actions in physiological and path-ological microenvironments.In recent years,intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery,biological barrier circumvention,multi-responsive tumor sensing and drug release,as well as convergence with precise medication approaches such as personalized tumor vaccines.On the other hand,the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in charac-terization,monitoring and clinical use,requesting a more comprehensive and dynamic understanding of nano-bio interactions.This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery,tumor immunotherapy and temporospatially specific tumor imaging,as well as impor-tant advances of our knowledge on their interaction with biological systems.In the perspective of clinical translation,we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nano-materials,highlighting the critical importance clinically-oriented system design.展开更多
National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental an...National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental and applied researches in the field of nanoscience and technology,especially those with important potential applications.NCNST is operated under the supervision of the Governing Board and aims to become a world-class research center,as well as public technological platform and young talents training center in the field,and to act as an important bridge for international academic exchange and collaboration.The NCNST currently has three CAS Key Laboratories:the CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,the CAS Key Laboratory for Standardization and Measurement for Nanotechnology and the CAS Key Laboratory for Nanosystem and Hierarchical Fabrication.In 2020,the CAS Key Laboratory of Nanophotonic Materials and Devices started construction.Besides,there are Division of Nanotechnology Development,Nanofabrication Laboratory,Intelligent Nanosensing Laboratory and Theoretical Laboratory.展开更多
Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosen...Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.展开更多
Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the...Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.展开更多
Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates incl...Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.展开更多
Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in con...Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in conventional mitochondrial targeting strategies,we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin(DOX)resistance in lung cancer.Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors.As a consequence,thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice.This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.展开更多
Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen,thus efficiently facilitating antitumor adaptive immunity.Bacteria-derived outer membrane ves...Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen,thus efficiently facilitating antitumor adaptive immunity.Bacteria-derived outer membrane vesicles(OMVs)are an excellent candidate due to their abundance of pathogen associated molecular patterns.However,during the uptake of OMVs by dendritic cells(DCs),the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage,a phenomenon we refer to as“maturation-induced uptake obstruction"(MUO).Herein we decorated OMV with the DC-targeting aDEC205 antibody(OMV-DEC),which endowed the nanovaccine with an uptake mechanism termed as 4<not restricted to maturation via antibody modifying”(Normandy),thereby overcoming the MUO phenomenon.We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display.In summary,this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines,and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.展开更多
Knowledge on the interactions between engineered nanomaterials(ENMs) and biological systems is critical both for the assessment of biological effects of ENMs and for the rational design of ENM-based products. However,...Knowledge on the interactions between engineered nanomaterials(ENMs) and biological systems is critical both for the assessment of biological effects of ENMs and for the rational design of ENM-based products. However, probing the events that occur at the nano-bio interface remains extremely challenging due to their complex and dynamic nature. So far, the understanding of mechanisms underlying nano-bio interactions has been mainly limited by the lack of proper analytical techniques with sufficient sensitivity, selectivity and resolution for characterization of nano-bio interface events. Moreover, many classic bioanalytical methods are not suitable for direct measurement of nano-bio interface interactions. These have made establishing analytical methodologies for systematic and comprehensive study of nano-bio interface one of the most focused areas in nanobiology. In this review we have discussed some representative developments regarding analytical techniques for nano-bio interface characterization, including the improvements of traditional methods and the emergence of powerful new technologies. These developments have allowed ultrasensitive, real-time analysis of interactions between ENMs and biomolecules, transformations of ENMs in biological environment, and impacts of ENMs on living systems on molecular or cellular level.展开更多
Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents,extensive efforts have been devoted to the development of more potent macromolecular agents with highs...Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents,extensive efforts have been devoted to the development of more potent macromolecular agents with highspecificity.Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomesand inhibiting protein synthesis.Nonetheless,its poor internalization ability to tumor cells has compromisedthe therapeutic promise of gelonin.In this study,a tumor acidity-responsive intracellular protein deliverysystem-functional gelonin(Trx-pHLIP-Gelonin,TpG)composed of a thioredoxin(Trx)tag,a pH low insertionpeptide(pHLIP)and gelonin,was designed and obtained by genetic recombination technique for the first time.TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cellproliferation via triggering cell apoptosis and inhibiting protein synthesis.Most importantly,treatment byintravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much moreeffective than gelonin in curtailing tumor growth rates with negligible toxicity.Collectively,our present worksuggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficientdelivery of other bioactive substances to acidic diseased tissues.展开更多
Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy.Among vascular coagulation agents,the extracellular domain of coagulation-inducing protein tissue factor,truncated tis...Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy.Among vascular coagulation agents,the extracellular domain of coagulation-inducing protein tissue factor,truncated tissue factor(tTF),is the most widely used.Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation,free tTF cannot be used for cancer treatment on its own but must be combined with other moieties.We here developed a novel,tumor-specific tTF delivery system through coupling tTF with the DNA aptamer,AS1411,which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells.Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors,thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects.This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.展开更多
The high incidence rates and complicated subtypes of prostate cancer(PCa)call for the demand of the precise diagnostic and therapeutic strategies.Current clinical imaging techniques,such as MRI,CT,and ultrasonography ...The high incidence rates and complicated subtypes of prostate cancer(PCa)call for the demand of the precise diagnostic and therapeutic strategies.Current clinical imaging techniques,such as MRI,CT,and ultrasonography are difficult to accurately detect the early-stage tumor lesions,and biochemical assays or biopsies are invasive and cannot provide sufficient information for the PCa staging and classification.Nanotechnology has the potential to improve the accuracy of current diagnosis strategies by targeting specific PCa biomarkers and/or integrating multiple imaging modes.In this review,we briefly introduce current clinical PCa imaging strategies and their major limitations,and highlight representative works on nanoparticle-mediated multimode imaging strategies.We also discuss the challenges of nanotechnology-based PCa diagnosis,and come up with suggestions and perspectives.展开更多
文摘Au-Ft,as a green synthesized nanoparticle,is composed of a ferritin nanocage enclosing a pair of Au nanoclusters inside.Our previous study has demonstrated that Au-Ft can be an excellentfluorescent probe for whole body imaging of mice with kidney specific targeting.But,the accuratelocalization of Au-Ft in kidney is still absent.In the current study,we detected and assessed the cellular and subcellular localization of Au-Ft in renal cortex and medulla of nu/nu mice after tailvein injection by using Nuance optical system(CRi,Woburn,USA)and inForm intelligent image analysis soft ware based on single cell segmentation.We obtained the fluorescence intensity and cellular location of kidney-targeting Au-Ft probe in particular cell of renal glomerulus or renaltubules,which provided valuable proofs to clarify the mechanism of Au-Ft selective enrichment in kidney and the associated metabolic processes.
基金sponsored by the National Natural Science Foundation of China(52173120,21877023,32271391)the Youth Innovation Promotion Association CAS(2021018,China)+1 种基金the Beijing Natural Science Foundation(L222015,China)the Beijing Nova Program(20220484233,China)。
文摘As a representative chemotherapeutic drug,docetaxel(DTX)has been used for breast cancer treatment for decades.However,the poor solubility of DTX limits its efficacy,and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4(CXCR4)expression during the treatment.Herein,we conjugated CXCR4 antagonist peptide(CTCE)with DTX(termed CTCE-DTX)as an anti-metastasis agent to treat breast cancer.CTCE-DTX could selfassemble to nanoparticles,targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy.Thus,the CTCE-DTX NPs achieved promising efficacy on inhibiting both bonespecific metastasis and lung metastasis of triple-negative breast cancer.Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.
基金supported by grants from the National Natural Science Foundation of China(Nos.32000998,and 32201240)The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(No.2022HYTP046)+2 种基金the China Postdoctoral Science Foundation(Nos.2019TQ0285,2019M662513,and 2021TQ0298)Henan provincial Medical Science and Technology Research Project(No.LHGJ20210210)Science and Technology Development Project of Henan Province(Nos.212102310138 and 222102310525).
文摘Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of GrB.To circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer chemo-immunotherapy.In vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ICD.Meanwhile,D3RL can competitively relieve the inhibition of Sb9 to GrB.The restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor effect.Taken together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.
基金supported in part by the National Natural Science Foundation of China(Nos.31971305 and 21905196)Fundamental Research Funds for the Central University(Nos.buctrc201915 and XK1802-8).
文摘Interfacial assembly has been intensively investigated in fabricating biomaterials and nanodevices for various applications.Recently,due to the precise sequence programmability,unique molecular recognition ability,and good biocompatibility,deoxyribonucleic acid(DNA)has been explored as superior building blocks to assemble at bio-interface for manipulating biological entities.To the best of our knowledge,the advances in this area have not been systematically summarized.To provide an overview of the area,in this review,the recently developed DNA assembly strategies on bio-interfaces were well summarized,and their representative works are exampled to illustrate how to rationally and elaborately design DNA molecules to realize functional integration and emerging of novel biological functionalities with high controllability and programmability.Furthermore,the biomedical applications of DNA assembly at bio-interface are categorially elaborated.The fascinating and unique advantages of DNA assembly systems are fully discussed in the exemplified applications to show the distinguished perspective of DNA in the future development.At the end of this review,the current limitations and challenges in applications and potential improvement strategies for DNA assembly at bio-interface are fully discussed.The future development direction is deliberated.We envision that this review will help scientists in the interdisciplinary fields gain a more comprehensive understanding of the DNA assembly at bio-interface,and therefore jointly promote the advances in this field.
基金sponsored by the National Natural Science Foundation of China(Nos.52173120 and 21877023)the Youth Innovation Promotion Association CAS(No.2021018)+2 种基金the Beijing Natural Science Foundation(No.L222015)the Key Area R&D Program of Guangdong Province(No.2020B0101020004)the Beijing Nova Program(No.20220484233).
文摘Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic HCC.HSCs play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver fibrosis.CAFs can be derived from activated HSCs and differentiate into ECM-producing myofibroblasts.Moreover,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune response.Combined therapeutic strategies show reduced drug resistance and side effects.Nanotechnology-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple mechanisms.In this review,we will discuss recent developments in combinational strategies based on nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC treatment.We will also identify the major challenges that the field is facing and offer some insights for future drug discovery.
基金supported by the National Basic Research Plan of China(2018YFE0205300)the National Basic Science Center Project(T2288102)the Key Area Research and Development Program of Guangdong Province(2020B0101020004).
文摘Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated na-ture of cancer.With rationally designed multifunctionality and programmable assembly of functional subunits,the in vivo behaviors of intelligent nanosystems have become increasingly tunable,making them more efficient in performing sophisticated actions in physiological and path-ological microenvironments.In recent years,intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery,biological barrier circumvention,multi-responsive tumor sensing and drug release,as well as convergence with precise medication approaches such as personalized tumor vaccines.On the other hand,the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in charac-terization,monitoring and clinical use,requesting a more comprehensive and dynamic understanding of nano-bio interactions.This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery,tumor immunotherapy and temporospatially specific tumor imaging,as well as impor-tant advances of our knowledge on their interaction with biological systems.In the perspective of clinical translation,we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nano-materials,highlighting the critical importance clinically-oriented system design.
文摘National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental and applied researches in the field of nanoscience and technology,especially those with important potential applications.NCNST is operated under the supervision of the Governing Board and aims to become a world-class research center,as well as public technological platform and young talents training center in the field,and to act as an important bridge for international academic exchange and collaboration.The NCNST currently has three CAS Key Laboratories:the CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,the CAS Key Laboratory for Standardization and Measurement for Nanotechnology and the CAS Key Laboratory for Nanosystem and Hierarchical Fabrication.In 2020,the CAS Key Laboratory of Nanophotonic Materials and Devices started construction.Besides,there are Division of Nanotechnology Development,Nanofabrication Laboratory,Intelligent Nanosensing Laboratory and Theoretical Laboratory.
基金supported by grants from the National Basic Research Plan of China(grant no.2018YFA0208900)the National Natural Science Foundation of China(grant nos.32000998,32000996,,U2004123)+1 种基金The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(grant no.2022HYTP046)the China Postdoctoral Science Foundation(grant nos.2019TQ0285,2019M662513,2020M682358,2020TQ0280,2021TQ0298).
文摘Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.
基金supported by the National Natural Science Foundation of China (11621505, 11435002, 31671016)
文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.
基金Acknowledgments This work was supported by the National Basic Research Program of China (2012CB934004), the National Funds for Distinguished Young Scientists (31325010), the Key Research Program of the Chinese Academy of Sciences (KGZD-EW-T06) and the National Natural Science Foundation of China (31300822).
基金supported by the National Natural Science Foundation of China(91127043,31600803,and 21273051)
文摘Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.
基金We are grateful to Beijing Natural Science Foundation(7212212)National Natural Science Foundation of China(11875269 and 21574136)Hundred Talents Program of CAS for financial support。
文摘Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in conventional mitochondrial targeting strategies,we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin(DOX)resistance in lung cancer.Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors.As a consequence,thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice.This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.
基金the National Key R&D Program of China(Grants No.2018YFA0208900,2018YFE0205300,and 2021YFA0909900)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB36000000)+5 种基金the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-010)the Beijing Natural Science Foundation of China(Grant No.Z200020)the Beijing Nova Program(Z201100006820031)the National Natural Science Foundation of China(Grants No.32171384,31800838,31820103004,31730032,and 51861145302)the Key Research Project of Frontier Science of the Chinese Academy of Sciences(Grant No.QYZDJ-SSW-SLH022)the Innovation Research Group of National Natural Science Foundation(Grant No.11621505).
文摘Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen,thus efficiently facilitating antitumor adaptive immunity.Bacteria-derived outer membrane vesicles(OMVs)are an excellent candidate due to their abundance of pathogen associated molecular patterns.However,during the uptake of OMVs by dendritic cells(DCs),the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage,a phenomenon we refer to as“maturation-induced uptake obstruction"(MUO).Herein we decorated OMV with the DC-targeting aDEC205 antibody(OMV-DEC),which endowed the nanovaccine with an uptake mechanism termed as 4<not restricted to maturation via antibody modifying”(Normandy),thereby overcoming the MUO phenomenon.We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display.In summary,this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines,and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.
基金supported by the National Natural Science Foundation of China (21320102003, 31200752, 31661130152, 11435002)the National Distinguished Young Scientists Program (31325010)
文摘Knowledge on the interactions between engineered nanomaterials(ENMs) and biological systems is critical both for the assessment of biological effects of ENMs and for the rational design of ENM-based products. However, probing the events that occur at the nano-bio interface remains extremely challenging due to their complex and dynamic nature. So far, the understanding of mechanisms underlying nano-bio interactions has been mainly limited by the lack of proper analytical techniques with sufficient sensitivity, selectivity and resolution for characterization of nano-bio interface events. Moreover, many classic bioanalytical methods are not suitable for direct measurement of nano-bio interface interactions. These have made establishing analytical methodologies for systematic and comprehensive study of nano-bio interface one of the most focused areas in nanobiology. In this review we have discussed some representative developments regarding analytical techniques for nano-bio interface characterization, including the improvements of traditional methods and the emergence of powerful new technologies. These developments have allowed ultrasensitive, real-time analysis of interactions between ENMs and biomolecules, transformations of ENMs in biological environment, and impacts of ENMs on living systems on molecular or cellular level.
基金National Natural Science Foundation of China(No.31500771,31770382)Research Project Supported by Shanxi Scholarship Council of China(No.2021-016)+2 种基金Natural Science Foundation of Shanxi Province(No.201901D111007,201901D111013)foreign experts project of Shanxi Provincial“100 Talents Plan”(Prof.Roland H Stauber)graduate education innovation project of Shanxi Province(2021Y120).
文摘Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents,extensive efforts have been devoted to the development of more potent macromolecular agents with highspecificity.Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomesand inhibiting protein synthesis.Nonetheless,its poor internalization ability to tumor cells has compromisedthe therapeutic promise of gelonin.In this study,a tumor acidity-responsive intracellular protein deliverysystem-functional gelonin(Trx-pHLIP-Gelonin,TpG)composed of a thioredoxin(Trx)tag,a pH low insertionpeptide(pHLIP)and gelonin,was designed and obtained by genetic recombination technique for the first time.TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cellproliferation via triggering cell apoptosis and inhibiting protein synthesis.Most importantly,treatment byintravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much moreeffective than gelonin in curtailing tumor growth rates with negligible toxicity.Collectively,our present worksuggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficientdelivery of other bioactive substances to acidic diseased tissues.
基金supported by the National Distinguished Young Scientists Program (No.31325010)the National Natural Science Foundation of China (No.31730032)+1 种基金the Innovation Research Group of National Natural Science Foundation of China (No.11621505)the Key Research Project of Frontier Science of the Chinese Academy of Sciences (No.QYZDJ-SSW-SLH022).
基金supported by grants from the National R&D Program of China(2018YFE0205300,2018YFA0208900)the National Natural Science Foundation of China(81871489,91859118,31730032,31700870,31470969,31661130152)+2 种基金the National Distinguished Young Scientist program(31325010,China)the K.C.Wong Education Foundation(GJTD-2018-03,China)the Beijing Municipal Natural Science Foundation(7182126,China)
文摘Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy.Among vascular coagulation agents,the extracellular domain of coagulation-inducing protein tissue factor,truncated tissue factor(tTF),is the most widely used.Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation,free tTF cannot be used for cancer treatment on its own but must be combined with other moieties.We here developed a novel,tumor-specific tTF delivery system through coupling tTF with the DNA aptamer,AS1411,which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells.Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors,thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects.This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.
基金supported by the National Key R&D Program of China(2021YFA0909900)。
文摘The high incidence rates and complicated subtypes of prostate cancer(PCa)call for the demand of the precise diagnostic and therapeutic strategies.Current clinical imaging techniques,such as MRI,CT,and ultrasonography are difficult to accurately detect the early-stage tumor lesions,and biochemical assays or biopsies are invasive and cannot provide sufficient information for the PCa staging and classification.Nanotechnology has the potential to improve the accuracy of current diagnosis strategies by targeting specific PCa biomarkers and/or integrating multiple imaging modes.In this review,we briefly introduce current clinical PCa imaging strategies and their major limitations,and highlight representative works on nanoparticle-mediated multimode imaging strategies.We also discuss the challenges of nanotechnology-based PCa diagnosis,and come up with suggestions and perspectives.