Sonodynamic therapy (SDT) is a noninvasive approach to tumor treatment, with ongoing efforts being focused on developing highly effective sonosensitizers with low toxicity. Herein, a liquid-phase stripping technique was introduced as a simple reflux method for synthesizing ultrasmall Mn-PCN-224 nanodots (MM NDs). Compared with PCN-224 nanodots, the synthesized MM NDs, which function as renal-clearable nanoagents, produced 2.42 times more reactive oxygen species (ROS) under identical ultrasound (US) irradiation conditions. In vivo and in vitro experiments revealed that A549 lung cancer cells treated with MM NDs under US irradiation and H