Radiosensitizer-based injectable hydrogel for enhanced radio-chemotherapy of TNBC

Radionuclide therapy (RNT) stands out as a highly effective method for treating solid tumors. However, its therapeutic efficiency faces challenges due to the radioresistance of tumors, the limited penetration depth and intracellular deposition of rays in tumor tissue, which causes residue of living cancer cells. Herein, we report a novel approach by utilizing radionuclide ¹³¹I-labelled polydopamine encapsulated gold nanoparticle co-loaded with the classical anticancer drug gemcitabine within a hydrogel formed from oxidized glucan and chitosan hydrochloride, combining RNT with chemotherapy for cancer treatment. Au, as a high Z element, is able to interact with short-range β-rays to emit bremsstrahlung and secondary charged particles which in turn increase the dose deposited in tumor cells. Simultaneously, gemcitabine is able to affect cell cycle redistribution, resulting in an increase in the radiosensitive cellular component of the cycle, and gemcitabine also inhibits the repair of radioactive damage to cellular DNA, which has a radiosensitizing effect. In both in vivo and vitro experiments, the injectable hydrogel demonstrates excellent biosecurity, stability in radionuclide labeling, and capabilities for single-photon emission computed tomography (SPECT) imaging. Compared analysis with single RNT revealed that combination therapy markedly inhibits the growth of triple-negative breast cancer. This integrated therapeutic strategy establishes an efficient tumor synergistic treatment platform, offering new avenues for advancing radionuclide therapy in the clinical treatment of cancer.