The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functio...The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase(CAT),chlorin e6(Ce6) and metal-phenolic network(MPN) capsule.It is demonstrated that the CAT encapsulated in the capsules(named CCM capsules) could catalyze the degradation of hydrogen peroxide(H;O;) to produce molecular oxygen(O;),which could be converted into cytotoxicity reactive oxygen species(ROS) by surface-loaded Ce6 under 660 nm laser irradiation,leading to synergistic anticancer effects in vitro and in vivo.Therefore,the application of CCM capsule could be a promising strategy to improve PDT effectiveness.展开更多
Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of S...Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist(i.e.,SR717)and a chemotherapeutic drug(i.e.,curcumin).After intravenous administration,the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses.Meanwhile,the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1,leading to the reversal of the immunosuppressive TME.The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary,recurrent,and metastatic tumors.The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.展开更多
基金supported by the Innovation Project of Jinan Science and Technology Bureau (No. 2020GXRC022)the Project for Scientific Research Innovation Team of Young Scholar in Colleges and Universities of Shandong Province (No. 2020KJC001)the National Natural Science Foundation of China (No. 21677090)。
文摘The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase(CAT),chlorin e6(Ce6) and metal-phenolic network(MPN) capsule.It is demonstrated that the CAT encapsulated in the capsules(named CCM capsules) could catalyze the degradation of hydrogen peroxide(H;O;) to produce molecular oxygen(O;),which could be converted into cytotoxicity reactive oxygen species(ROS) by surface-loaded Ce6 under 660 nm laser irradiation,leading to synergistic anticancer effects in vitro and in vivo.Therefore,the application of CCM capsule could be a promising strategy to improve PDT effectiveness.
基金Shandong Traditional Chinese Medicine Technology Project,Grant/Award Number:Q-2023127Innovation Project of Jinan Science and Technology Bureau,Grant/Award Number:2020GXRC022+2 种基金Project for Scientific Research Innovation Team of Young Scholars in Colleges and Universities of Shandong Province,Grant/Award Numbers:2020KJC001,2022KJ196National Natural Science Foundation of China,Grant/Award Number:22372091Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2023MB081。
文摘Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist(i.e.,SR717)and a chemotherapeutic drug(i.e.,curcumin).After intravenous administration,the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses.Meanwhile,the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1,leading to the reversal of the immunosuppressive TME.The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary,recurrent,and metastatic tumors.The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.
