Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during c...Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.展开更多
Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors i...Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.展开更多
Monitoring dynamic changes in tumor immune markers are essential for predicting the therapeutic responses of tumors to immunotherapy, as well as other traditional therapies, such as chemotherapy and radiotherapy. Here...Monitoring dynamic changes in tumor immune markers are essential for predicting the therapeutic responses of tumors to immunotherapy, as well as other traditional therapies, such as chemotherapy and radiotherapy. Here, we designed a lipid-aptamer conjugate by employing a C18 chain to modify an aptamer targeting programmed cell death-ligand 1(C18-ap PDL1). The obtained C18-ap PDL1 could bind with serum albumin postintravenous injection to achieve prolonged blood circulation and enhanced in vivo stability without weakening its binding affinity toward PDL1. C18-ap PDL1 labeling with radionuclides, such as;Tc, could yield a nuclear imaging agent exhibiting much higher tumor-homing ability than bare aptamer. Notably, such radiolabeled C18-ap PDL1 could be utilized to visually monitor the dynamic changes in PDL1 expression postchemotherapy or radiotherapy within a few hours. Additionally, this C18-ap PDL1 could offer improved antitumor immune therapeutic responses,which are comparable with those of commercial anti-PDL1 antibodies at the same weight dosage. Thus, this article presented promising lipid-modified aptamers for cancer immunoimaging and immunotherapy.展开更多
基金partially supported by the National Natural Science Foundation of China(51802209,22077093,51761145041,51525203)the National Research Programs from Ministry of Science and Technology(MOST)of China(2016YFA0201200)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20180848)the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.
基金This work was partially supported by the National Natural Science Foundation of China(No.22077093)the National Research Programs from Ministry of Science and Technology(MOST)of China(Nos.2021YFF0701800 and 2022YFF0706500)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220110)the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Suzhou Key Laboratory of Nanotechnology and Biomedicine,and the 111 Program from the Ministry of Education of China。
文摘Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.
基金supported by the National Natural Science Foundation of China (32101149, 91959104, 21927803, 52032008, 51903182, 51572180)the China Postdoctoral Science Foundation (2020M671143)+3 种基金a Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, Jiangsu Social Development Project (BE2019658)Suzhou Key Laboratory of Nanotechnology and BiomedicineCollaborative Innovation Center of Suzhou Nano Science & Technologythe Program of Introducing Talents of Discipline to Universities of China。
文摘Monitoring dynamic changes in tumor immune markers are essential for predicting the therapeutic responses of tumors to immunotherapy, as well as other traditional therapies, such as chemotherapy and radiotherapy. Here, we designed a lipid-aptamer conjugate by employing a C18 chain to modify an aptamer targeting programmed cell death-ligand 1(C18-ap PDL1). The obtained C18-ap PDL1 could bind with serum albumin postintravenous injection to achieve prolonged blood circulation and enhanced in vivo stability without weakening its binding affinity toward PDL1. C18-ap PDL1 labeling with radionuclides, such as;Tc, could yield a nuclear imaging agent exhibiting much higher tumor-homing ability than bare aptamer. Notably, such radiolabeled C18-ap PDL1 could be utilized to visually monitor the dynamic changes in PDL1 expression postchemotherapy or radiotherapy within a few hours. Additionally, this C18-ap PDL1 could offer improved antitumor immune therapeutic responses,which are comparable with those of commercial anti-PDL1 antibodies at the same weight dosage. Thus, this article presented promising lipid-modified aptamers for cancer immunoimaging and immunotherapy.
