Magnetic Nanodroplets for Enhanced Deep Penetration of Solid Tumors and Simultaneous Magnetothermal-Sensitized Immunotherapy against Tumor Proliferation and Metastasis
作者全名："Wang, Junrui; Zhang, Wenli; Xie, Zhuoyan; Wang, Xingyue; Luo, Ying; Jiang, Weixi; Liu, Yun; Wang, Zhigang; Ran, Haitao; Song, Weixiang; Guo, Dajing"
作者地址："[Wang, Junrui; Zhang, Wenli; Luo, Ying; Liu, Yun; Song, Weixiang; Guo, Dajing] Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Zhang, Wenli; Luo, Ying; Jiang, Weixi; Wang, Zhigang; Ran, Haitao] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Zhang, Wenli; Luo, Ying; Jiang, Weixi; Wang, Zhigang; Ran, Haitao] Chongqing Med Univ, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Xie, Zhuoyan] Chongqing Peoples Hosp, Dept Ultrasound, Chongqing 400014, Peoples R China; [Wang, Xingyue] Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Affiliated Hosp, Xiangyang 441053, Hubei, Peoples R China"
通信作者："Song, WX; Guo, DJ (通讯作者)，Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."
来源：ADVANCED HEALTHCARE MATERIALS
文献类型：Article; Early Access
关键词：immunotherapy; magnetic droplet vaporization; magnetic fluid hyperthermia; nanoultrasonic biomedicines; solid tumors
摘要："The central cells of solid tumors are more proliferative and metastatic than the marginal cells. Therefore, more intelligent strategies for targeting cells with deep spatial distributions in solid tumors remain to be explored. In this work, a biocompatible nanotheranostic agent with a lipid membrane-coated, Fe3O4 and perfluoropentane (PFP)-loaded, cRGD peptide (specifically targeting the integrin alpha v beta 3 receptor)-grafted, magnetic nanodroplets (MNDs) is developed. The MNDs exhibit excellent magnetothermal conversion and controllable magnetic hyperthermia (MHT) through alternating magnetic field regulation. Furthermore, MHT-mediated magnetic droplet vaporization (MDV) induces the expansion of the MNDs to transform them into ultrasonic microbubbles, increasing the permeability of tissue and the cell membrane via the ultrasound-targeted microbubble destruction (UTMD) technique and thereby promoting the deep penetration of MNDs in solid tumors. More importantly, MHT not only causes apoptotic damage by downregulating the expression of the HSP70, cyclin D1, and Bcl-2 proteins in tumor cells but also improves the response rate to T-cell-related immunotherapy by upregulating PD-L1 expression in tumor cells, thus inhibiting the growth of both primary and metastatic tumors. Overall, this work introduces a distinct application of nanoultrasonic biomedicine in cancer therapy and provides an attractive immunotherapy strategy for preventing the proliferation and metastasis of deeply distributed cells in solid tumors."
基金机构："National Natural Science Foundation of China [81971608, 81801718]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [CQYC2020030389, 2020-7]; Chongqing Talents Program [cstc2021ycjh-bgzxm0168]; General Program of Chongqing Natural Science Foundation [cstc2020jcyjmsxmX1017]; Postgraduate Research and Innovation Projects of Chongqing Municipal Education Commission [CYB21177, CYB20154]"
基金资助正文："J.W. and W.Z. should be considered co-first authors. J.W. and W.Z. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (81971608, 81801718) and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (CQYC2020030389, 2020-7). The authors also appreciate the Chongqing Talents Program (cstc2021ycjh-bgzxm0168), the General Program of Chongqing Natural Science Foundation (cstc2020jcyjmsxmX1017), and the Postgraduate Research and Innovation Projects of Chongqing Municipal Education Commission (CYB21177, CYB20154). The authors also appreciate American Journal Experts (AJE) for their assistance with language editing (A4CC-9D78-63F2-BA0E-BFFP)."