An injectable cisplatin hydrogel effectively suppresses tumors while preserving anti-infective immunity

• Systemic administration of cisplatin suppresses anti-infective T-cell immunity. • CDDP@AHIC achieves potent antitumor efficacy without causing immunosuppression. • Preserving host immunity is key to developing safer, more effective chemotherapy.​. In clinical settings, cisplatin (CDDP) administration causes immune suppression, rendering patients more susceptible to infection. Herein, systemic administration of CDDP substantially reduced the number and proliferative capacity of cluster of differentiation (CD)4 + and CD8 + T cells in the periphery of mice, and reduced the secretion of proinflammatory cytokines, such as interferon (IFN)-γ. To alleviate these toxic side effects, an injectable hydrogel was designed for the topical administration and sustained release of CDDP. The hydrogel was based on iminodiacetic acid-modified oxidized hyaluronic acid cross-linked with carboxymethyl chitosan (AHIC) and named CDDP@AHIC. The hydrogel exhibited promising anti-tumor effects, prevented damage, and suppressed the systemic protective immune response in tumor-bearing mice injected with B16 melanoma cells. When tumor-bearing mice treated with CDDP@AHIC were challenged with Listeria monocytogenes , mouse mortality was considerably inhibited. Notably, mice topically administered CDDP@AHIC had the same levels of IFN-γ production as the control mice, whereas mice systemically administered CDDP had impaired T cell immunity. Overall, CDDP@AHIC provides an alternative strategy for inhibiting tumor growth while maintaining protective T-cell immunity to resist infections. In addition, this drug release system may be useful for local treatment with other chemotherapeutic drugs.