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MMP-2 and upconverted UV dual-mediated drug sequential delivery and on-site immobilization for enhanced multidrugresistant cancer therapy

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Science China Chemistry 2023年第8期66卷 2317-2328页

作者： Anna Wang Jing Fang Yali Feng Yuqi Zhang Yan Zhao Jiachen Li Chaoxiang Cui Yi Hou Haibin Shi Mingyuan Gao State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou215123China Institute of Chemistry Chinese Academy of Sciences Beijing100190China

Controlled drug delivery holds great potential for effective tumor treatment owing to the merits of overcoming drug resistance and improving therapeutic efficacy while minimizing systemic toxicity.However,accurate and controllable delivery of chemotherapeutics into tumor tissue with high efficiency remains a huge challenge.Taking advantage of the UV-emitting characteristics of upconversion nanoparticles(UCNPs),herein we for the first time report an MMP-2 enzyme and near infrared(NIR)dual-mediated sequential drug delivery and in-situ immobilization(ENDDI)system that is fabricated by decorating UCNPs with MMP-2 responsive and photocrosslinkable peptide bearing anticancer drug doxorubicin(DOX)for overcoming multidrug resistance.Upon cleavage with tumor-specific MMP-2,the peptide fragment containing a photolabile benzophenone(BP)and DOX could be released and in-situ immobilized within the tumor through the covalent crosslinking reaction between BP and neighboring biomolecules under the excitation of converted UVemission from UCNPs,which remarkably blocks the exocytosis of DOX leading to prolonged drug retention,achieving significant suppression of DOX-resistant breast tumors.Our current dual stimuli-mediated sequential drug delivery and in-situ immobilization represent a generalizable strategy for the effective treatment of multidrug resistant tumors.

关键词： upconversion nanoparticles photocrosslinking drug delivery in situ immobilization multidrug resistance

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