<sup>211</sup>At-Labeled Nanoscale Polydopamine Decorated with FAPI for Synergistic Targeted-Alpha Therapy and Photothermal Therapy of Glioma
Feize Li, Huan Ma, Hao Luo, Guohua Shen, Jing Su, Huawei Cai, Xijian Chen, Tu Lan, Yuanyou Yang, Jiali Liao, Ning Liu
Abstract
How to boost the therapeutic efficiency is still the key to translation of anticancer nanomedicine from preclinical investigations to clinical practice. In this work, we proposed to integrate 211 At-derived targeted-alpha therapy (TAT) and photothermal therapy (PTT) into nanoscale polydopamine (PDA), attempting to obtain a feasible solution to circumvent the barriers both in 211 At-based endoradiotherapy and common nanomedicine. After radiolabeling with 211 At and fibroblast activation protein inhibitor (FAPI) decoration of PDA nanoparticles, the obtained 211 At-PDA-FAPI exhibits considerable photothermal conversion efficiency, high radioactive stability, excellent cancer affinity, and remarkable antitumor ability. The synergistic TAT-PTT therapeutic effect of 211 At-PDA-FAPI in murine xenograft models of glioma has been well confirmed, with the tumor growth inhibition values of 80.82, 76.70, and 96.71% at 15 days postinjection for PTT, TAT, and TAT-PTT treatments, respectively. Meanwhile, the TAT-PTT regimen can prolong the median survival of tumor-bearing mice two times from 18 to 36 days, without detectable biotoxicity during the whole treatment. The outcome of this work provides important hints for the design of therapeutic nanomedicine and the development of traditional radiopharmaceuticals.