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
Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emergin...Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications.Herein,2D NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG).Compared to their particulate counterpart,such 2D NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production,promising for chemotherapy and photodynamic therapy (PDT),respectively.Utilizing the porphyrin structure of TCPP,our 2D NMOFs could be labeled with a diagnostic radioisotope,99mTc,for single photon emission computer tomography (SPECT) imaging,which reveals efficient tumor homing of those 2D NMOFs upon intravenous injection.While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT,such 2D NMOFs show efficient biodegradation and rapid renal clearance.Our work presents the great promise of 2D NMOFs for nanomedicine applications.展开更多
Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordinat...Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordination nanosheets composed of Zn^(2+)and Tetrakis(4-carboxyphenyl)porphyrin(TCPP)are fabricated.While exhibiting greatly enhanced ultrasoundtriggered ROS generation useful for noninvasive SDT,such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynudeotides such as cytosine—phosphorothioate-guanine(CpG),which is a potent toll like receptor 9(TLR9)agonist useful in activating immune responses.Highly effective SD T of primary tumors could release tumor-associated antigens,which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses.Interestingly,ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment.Thus,SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SD T treatment.Moreover,SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors.Therefore,the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.展开更多
Nanoscale coordination polymers(NCPs)constructed by metal ions and organic ligands via metal–ligand bonds have attracted great attention for their biomedical application.Herein,a new type of NCP is constructed from Z...Nanoscale coordination polymers(NCPs)constructed by metal ions and organic ligands via metal–ligand bonds have attracted great attention for their biomedical application.Herein,a new type of NCP is constructed from Zn-ions and 4-phenylimidazole(PI),the latter of which is an inhibitor of indoleamine 2,3-dioxygenase(IDO)and acts as an organic bridging ligand via Zn–N coordination bonds.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the National Research Programs from Ministry of Science and Technology (MOST) of China (No.2016YFA0201200)the National Natural Science Foundation of China (Nos.51525203 and 51761145041)+1 种基金Collaborative Innovation Center of Suzhou Nano Science and Technologya Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.
文摘Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications.Herein,2D NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG).Compared to their particulate counterpart,such 2D NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production,promising for chemotherapy and photodynamic therapy (PDT),respectively.Utilizing the porphyrin structure of TCPP,our 2D NMOFs could be labeled with a diagnostic radioisotope,99mTc,for single photon emission computer tomography (SPECT) imaging,which reveals efficient tumor homing of those 2D NMOFs upon intravenous injection.While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT,such 2D NMOFs show efficient biodegradation and rapid renal clearance.Our work presents the great promise of 2D NMOFs for nanomedicine applications.
基金the National Research Programs of China(No.2016YFA0201200)the National Natural Science Foundation of China(Nos.91959104,21927803,51903182,51525203,)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20190826)Collaborative Innovation Center of Suzhou Nano Science and Technology,and the 111 Program from the Ministry of Education of China.
文摘Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordination nanosheets composed of Zn^(2+)and Tetrakis(4-carboxyphenyl)porphyrin(TCPP)are fabricated.While exhibiting greatly enhanced ultrasoundtriggered ROS generation useful for noninvasive SDT,such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynudeotides such as cytosine—phosphorothioate-guanine(CpG),which is a potent toll like receptor 9(TLR9)agonist useful in activating immune responses.Highly effective SD T of primary tumors could release tumor-associated antigens,which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses.Interestingly,ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment.Thus,SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SD T treatment.Moreover,SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors.Therefore,the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.
基金supported by the National Research Programs of China(no.2016YFA0201200)the National Natural Science Foundation of China(nos.51525203,51761145041,and 51572180)+2 种基金the China Postdoctoral Science Foundation(no.2020M671143)Collaborative Innovation Center of Suzhou Nano Science and Technology,a Jiangsu Natural Science Fund for Distinguished Young Scholars(no.BK20170063)and a Project Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,and a Project Funded for Postgraduate Research&Practice Innovation Program of Jiangsu Province(no.2019 SJKY19_2282).
文摘Nanoscale coordination polymers(NCPs)constructed by metal ions and organic ligands via metal–ligand bonds have attracted great attention for their biomedical application.Herein,a new type of NCP is constructed from Zn-ions and 4-phenylimidazole(PI),the latter of which is an inhibitor of indoleamine 2,3-dioxygenase(IDO)and acts as an organic bridging ligand via Zn–N coordination bonds.
