An Injectable Hydrogel with Stepwise Drug Release for Chemo-Photothermal Therapy of Tumors

Traditional chemotherapy drugs are not sustainably released and need to be administered multiple times, often leading to drug resistance and systemic toxicity. In this work, we designed a novel injectable hydrogel, made of chitosan and β-glycerophosphate, to codeliver chemotherapeutic drug mitoxantrone (MTO) and MTO-loaded PEGylated black phosphorus quantum dots (BP-PEG-MTO/MTO@Gel) for chemo-photothermal therapy of tumors with stepwise drug release. The hydrogel with a three-dimensional porous structure significantly enhanced drug loading and enabled a staged release of MTO. First, a large amount of MTO was released from the hydrogel, and BP-based photothermal therapy (PTT) can cause rapid ablation of local tumors. Second, the sustained release of MTO from BP has a long-term inhibitory effect against tumor growth. <i>In vitro</i> and <i>in vivo</i> evaluations confirmed that BP-PEG-MTO/MTO@Gel in the presence of PTT significantly enhanced the cytotoxic effect on tumor cells and inhibited tumor growth. The strategy uses an injectable hydrogel to combine chemotherapy and PTT with stepwise drug release on local tumors, showing a promising pathway for cancer therapy.