A Biodegradable “One‐For‐All” Nanoparticle for Multimodality Imaging and Enhanced Photothermal Treatment of Breast Cancer

Silver sulfide nanoparticles (Ag2S‐NP) hold promise for various optical‐based biomedical applications, such as near‐infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub‐5 nm Ag2S‐NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S‐NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S‐NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a “one‐for‐all” theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation. Ultrasmall silver sulfide nanoparticles are encapsulated within biodegradable PCPP polymers that offer size tunability. This innovative design enables the imaging of breast cancer through multiple modalities, while significantly improving the efficacy of photothermal treatment. As the polymeric nanoparticles gradually break down into harmless byproducts, the small metal cores are efficiently cleared from the body.