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

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Murphy, Neville and González‐Gómez, Roberto and Ashok, Nivethitha and O’Connell, Enda and Fearnhead, Howard and Tipping, William J. and Faulds, Karen and Tong, Wenming and Pandit, Abhay and Dwyer, Róisín M. and Graham, Duncan and Farràs, Pau (2025) Functionalizing injectable hydrogels with cobalt‐based metallacarboranes for targeted delivery in triple‐negative breast cancer. Chembiochem, 26 (21). e202500589. ISSN 1439-4227 (https://doi.org/10.1002/cbic.202500589)

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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.

ORCID iDs

Murphy, Neville, González‐Gómez, Roberto, Ashok, Nivethitha, O’Connell, Enda, Fearnhead, Howard, Tipping, William J. ORCID logoORCID: https://orcid.org/0000-0003-4273-2691, Faulds, Karen ORCID logoORCID: https://orcid.org/0000-0002-5567-7399, Tong, Wenming, Pandit, Abhay, Dwyer, Róisín M., Graham, Duncan ORCID logoORCID: https://orcid.org/0000-0002-6079-2105 and Farràs, Pau;
CORE (COnnecting REpositories)