Biodegradable and Piezoelectric Mn-Doped Hydroxyapatite for Sonodynamic Immunotherapy
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
Abstract
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.