A Smart Injectable Hydrogel Packaged with an Ion Channel Activator Molecule as a Targeted Delivery System for the Treatment of Cancer

Compared with conventional anticancer strategies, targeted therapy and drug delivery systems offer several benefits that enhance treatment efficacy, safety, and precision. However, their efficacy can be significantly constrained by the lack of suitable molecular targets, stability and drug release issues, financial burden, and potential drug-related toxicity. Bioelectricity plays a fundamental role in maintaining cellular homeostasis. Ion channels are key factors in regulating cellular bioelectricity, and pharmacological manipulation of these proteins has emerged as a promising anticancer strategy. In this study, we evaluated the effectiveness of a Smart Injectable Hydrogel as a delivery system for the Kv11.1 potassium (K+) activator molecule NS1643 (SIHD-Ka) in inhibiting cancer growth. SIHD-Ka consists of an injectable chitosan/pluronic hydrogel encapsulating NS1643. Our in vitro and in vivo experiments demonstrated that SIHD-Ka facilitates the sustained release of NS1643 at a constant rate under physiological conditions (37 °C) and effectively inhibits tumor growth in a triple-negative breast cancer (TNBC) model without eliciting notable adverse effects. These findings indicate that SIHD-Ka is a promising platform for the localized and controlled delivery of K+ channel activators, offering a targeted therapeutic strategy for the treatment of cancers.