Biodegradable and Piezoelectric Mn-Doped Hydroxyapatite for Sonodynamic Immunotherapy

作者：Lihan Cai, Fuping Han, Jun‐Ying Ding, Xiaofeng Zhou, Tiancong Shi, Fang Cheng, Chong Peng, Saran Long, Wen Sun, Jiangli Fan, Jianjun Du, Xiaojun Peng · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c06775 · 被引用次数：19 · 研究领域：Nanoplatforms for cancer theranostics、Heme Oxygenase-1 and Carbon Monoxide、Thermal Regulation in Medicine

The tumor microenvironment usually exhibits immunosuppressive characteristics, and pyroptosis is an effective method to stimulate antitumor immune responses. However, the current metal-ion-overload strategy to induce pyroptosis is hindered by the ion buffering system within the cell, which inhibits the release of exogenous ions. Herein, a biodegradable manganese-doped hydroxyapatite (Mn-HAP) with ultrasound (US) triggered continuous reactive oxygen species (ROS) modulation is proposed. Mn-HAP is defined as a sonoimmune stimulator because it functions as both a sonosensitizer and an immune agent. Before degradation, Mn-HAP exhibits an enhanced sonodynamic antitumor effect through the Mn-doping oxygen vacancies. Moreover, the built-in electric field induced by US activates the cell membrane-related ion channels and induces Ca 2+ influx. Following the degradation of Mn-HAP in the slightly acidic tumor microenvironment, the released Ca 2+ and ROS produced in sonodynamic therapy promote pyroptosis, while Mn 2+ activates the cGAS-STING pathway, triggering innate immunity and further enhancing the effect of pyroptosis-induced immunotherapy. This work provides a promising strategy for engineering biodegradable materials for the sonodynamic immunotherapy of solid tumors.