期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 34, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202102832
关键词
autophagy; enzymes; mild-temperature photothermal therapy; self-assembly; tumors
类别
资金
- National Natural Science Foundation of China [21725505, 81821001, 21673037]
- National Postdoctoral Program for Innovative Talents [BX20190068]
- China Postdoctoral Science Foundation [2020M671303]
Through rational design of a peptide-hydroxychloroquine conjugate, a smart strategy involving enzyme-triggered intracellular nanoparticle formation and HCQ release is proposed for autophagy-inhibited mild-temperature photothermal therapy of tumors. In vitro results demonstrate the conversion of the conjugate to a self-assembling nanoparticle and release of HCQ under dual enzyme catalysis, leading to exceptional therapeutic effects in vivo via intracellular nanoparticle formation and autophagy inhibition.
Mild-temperature photothermal therapy (PTT) of tumors has been intensively explored and adopted in preclinical/clinical trials in recent years. Nevertheless, tumor thermoresistance significantly compromises the therapeutic efficacy of mild-temperature PTT, and therefore, the extra addition of anti-thermoresistance agent is needed. Herein, by rational design of a peptide-hydroxychloroquine (HCQ) conjugate Cypate-Phe-Phe-Lys(SA-HCQ)-Tyr(H2PO3)-OH (Cyp-HCQ-Yp), a smart strategy of enzyme-triggered simultaneously intracellular photothermal nanoparticle formation and HCQ release is proposed for autophagy-inhibited mild-temperature PTT of tumor. In vitro results show that, under sequential catalysis of enzymes alkaline phosphatase and carboxylesterase, Cyp-HCQ-Yp is converted to Cypate-Phe-Phe-Lys(SA)-Tyr-OH (Cyp-Y) which self-assembles into its nanoparticle Cyp-NP and HCQ is released from Cyp-HCQ-Yp. By comparing with two control agents, it is validated that the exceptional therapeutic effect of Cyp-HCQ-Yp on tumor in vivo is achieved by its dual-enzyme-controlled intracellular nanoparticle formation and autophagy inhibition in tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据