Functionalizing Injectable Hydrogels with Cobalt-Based Metallacarboranes for Targeted Delivery in Triple-Negative Breast Cancer

Abstract

Cobalt-based metallacarboranes have emerged as potential candidates for cancer treatment owing to their unique structural properties. In this study, a biocompatible delivery platform is developed by noncovalently incorporating cobalt metallacarborane (CoSAN) into hyaluronic acid (HA) functionalized with lysine (Lys). HA-Lys 2 enables the electrostatic interaction of CoSAN while retaining its cytotoxic activity, as confirmed by cellular assays using MDA-MB-231 triple-negative breast cancer cells. Elemental mapping via energy-dispersive X-ray spectroscopy (EDX) confirms the successful and homogeneous incorporation of CoSAN to lead HA-Lys-CoSAN 3, and the composite is further characterized using diffusion-ordered nuclear magnetic resonance (NMR) spectroscopy (DOSY). Stimulated Raman scattering (SRS) microscopy data demonstrate comparable cellular uptake in MDA-MB-231 cells of free and HA-loaded CoSAN. Additionally, release studies under physiologically relevant conditions show a sustained release profile over 24 h with pH dependency to mimic normal and tumor microenvironments. The present study describes a viable method for integrating metallacarboranes into a polymeric drug delivery system without compromising their anticancer properties, thereby advancing their potential for future therapeutic use.