Injectable hydrogel for controlled anlotinib delivery and enhanced anti-tumor therapy in non-small cell lung cancer

• A self-healing injectable hydrogel was developed using natural biopolymers for the sustained delivery of anlotinib, a multi-target cancer therapeutic. • The hydrogel demonstrated strong mechanical strength, prolonged degradation, and excellent local adhesion for in situ tumor treatment. • In vitro and in vivo experiments confirmed its ability to inhibit tumor cell growth, migration, and blood vessel formation. • Comprehensive biosafety evaluations showed minimal systemic toxicity and good tissue compatibility, supporting its clinical potential. Non-small cell lung cancer (NSCLC) is one of the most frequently targeted cancers in precision therapy. However, maintaining high drug concentrations within the tumor microenvironment (TME) remains challenging with traditional drug delivery methods, often resulting in increased systemic toxicity and drug resistance. To address these issues, we developed a multifunctional hydrogel—OSA-TA-CMCS-anlotinib (OSTCA)—by combining oxidized sodium alginate (OSA), carboxymethyl chitosan (CMCS), tannic acid (TA), and anlotinib for controlled local drug release. The hydrogel exhibited excellent self-healing ability, injectability, and mechanical properties. Significant inhibition of NSCLC cell proliferation, migration, and invasion was observed in vitro. In vivo studies further demonstrated that the OSTCA hydrogel resulted in superior antitumor and anti-angiogenic effects compared to anlotinib monotherapy. Additionally, the hydrogel achieved sustained, localized release of anlotinib within the TME, thereby enhancing therapeutic efficacy and reducing systemic toxicity. The OSTCA hydrogel offers a promising and effective strategy for the local treatment of NSCLC, potentially overcoming the limitations of traditional systemic administration methods and providing new insights for future clinical applications.