A multifunctional hydrogel loaded with a BP/Bi2O3 heterojunction for enhanced radioimmunotherapy of breast cancer

Radiotherapy is a major treatment for breast cancer, but its efficacy is limited by insufficient local energy deposition, radioresistance, and weak systemic immune activation.Therefore, we developed a multifunctional hydrogel platform, HJ-CpG@Gel, integrating a black phosphorus/bismuth oxide heterojunction with the immunoadjuvant CpG-ODN to enhance breast cancer radioimmunotherapy. Stabilized BP/Bi2O3 HJ was prepared by in situ growth of Bi2O3 at defect-rich sites on black phosphorus quantum dots, which improved structural stability and enhanced reactive oxygen species (ROS) generation under X-ray irradiation. Furthermore, a hyaluronic acid-poly(vinyl alcohol) hydrogel crosslinked through dynamic boronate ester bonds was employed as the carrier to encapsulate both BP/Bi 2 O 3 HJ and CpG-ODN, yielding a multifunctional hydrogel with pH/H 2 O 2 -responsive degradation, self-healing properties, and injectability. The hydrogel released BP/Bi 2 O 3 HJ and CpG-ODN in response to the tumor microenvironment, facilitating markedly enhanced inhibition of 4T1 cell growth when combined with RT. In a bilateral 4T1 tumor mouse model, intratumoral injection of HJ-CpG@Gel with RT not only effectively reduced primary tumor size but also significantly delayed distant tumor progression by activating systemic immune responses. Moreover, the hydrogel demonstrated excellent biocompatibility and in vivo safety, as supported by both in vitro and in vivo evaluations, highlighting this integrated local-systemic therapeutic platform for breast cancer.