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 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.