Photodynamic therapy(PDT)has garnered significant attention as a promising approach to cancer therapy,harnessing the combined benefits of localized light treatment and the accompanying host immune response.In this stu...Photodynamic therapy(PDT)has garnered significant attention as a promising approach to cancer therapy,harnessing the combined benefits of localized light treatment and the accompanying host immune response.In this study,we engineered an immuno-enhanced PDT nanoplatform,denoted as HM@p-MOF(hybrid membrane@porphyrin-metal organic framework).The core porphyrin-MOF was cloaked with a hybrid membrane derived from B16F10 cancer cells and NK cells,resulting in enhanced stability.In both in vitro and in vivo experiments,our finding demonstrated that the hybrid membrane conferred dual targeting capabilities to the nanoplatform,leveraging the unique properties of the B16F10 membrane and NK membrane to augment immunogenic cell death(ICD)induced by photodynamic effects.Additionally,in conjunction with the immunomodulatory functions of the NK cell membrane,we observed an expansion of in situ immune infiltration leading to a systemic immune response.The HM@p-MOF nanoplatform exhibited the capacity to not only inhibit the growth of mouse melanoma but also suppress metastasis.This innovative HM@p-MOF nanoplatform present a viable strategy to enhance phototherapeutic efficacy for both localized and metastatic tumors.It provides a direction for the fabrication of biomimetic nanomedicines possessing immuno-modulatory function.展开更多
The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have att...The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22175107,22305140,51603184,82270531)Zhejiang Provincial Natural Science Foundation of China(Nos.LY21E030002,LY22H020003)+1 种基金Scientific Research Foundation of Zhejiang University City College(No.J-202104)Hangzhou Science and Technology Bureau of China(No.202203B27)。
文摘Photodynamic therapy(PDT)has garnered significant attention as a promising approach to cancer therapy,harnessing the combined benefits of localized light treatment and the accompanying host immune response.In this study,we engineered an immuno-enhanced PDT nanoplatform,denoted as HM@p-MOF(hybrid membrane@porphyrin-metal organic framework).The core porphyrin-MOF was cloaked with a hybrid membrane derived from B16F10 cancer cells and NK cells,resulting in enhanced stability.In both in vitro and in vivo experiments,our finding demonstrated that the hybrid membrane conferred dual targeting capabilities to the nanoplatform,leveraging the unique properties of the B16F10 membrane and NK membrane to augment immunogenic cell death(ICD)induced by photodynamic effects.Additionally,in conjunction with the immunomodulatory functions of the NK cell membrane,we observed an expansion of in situ immune infiltration leading to a systemic immune response.The HM@p-MOF nanoplatform exhibited the capacity to not only inhibit the growth of mouse melanoma but also suppress metastasis.This innovative HM@p-MOF nanoplatform present a viable strategy to enhance phototherapeutic efficacy for both localized and metastatic tumors.It provides a direction for the fabrication of biomimetic nanomedicines possessing immuno-modulatory function.
基金supported by the Vanke Special Fund for Public Health and Health Discipline Development,Tsinghua University(2022Z82WKJ005,2022Z82WKJ013)the Tsinghua University Spring Breeze Fund(2021Z99CFZ007)+2 种基金the National Natural Science Foundation of China(22175107)Funding by Tsinghua Universitythe Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006)。
文摘The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.