Functionalizing injectable hydrogels with cobalt-based metallacarboranes for targeted delivery in triple-negative breast cancer

Murphy, Neville, González-Gómez, Roberto, Ashok, Nivethitha, O’Connell, Enda, Fearnhead, Howard, Tipping, William J., Faulds, Karen, Tong, Wenming, Pandit, Abhay, Dwyer, Róisín M., Graham, Duncan, Farràs, Pau. (2025). Functionalizing Injectable Hydrogels with Cobalt-Based Metallacarboranes for Targeted Delivery in Triple-Negative Breast Cancer. ChemBioChem, 26(21), e202500589. https://doi.org/10.1002/cbic.202500589

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.

Funder

Research Ireland
European Union

Publisher

Wiley

Rights

CC BY

cb

Collections

School of Biological and Chemical Sciences (Scholarly Articles)