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

Neville Murphy; Roberto González‐Gómez; Nivethitha Ashok; Enda O’Connell; Howard Fearnhead; William J. Tipping; Karen Faulds; Wenming Tong; Abhay Pandit; Róisín M. Dwyer; Duncan Graham; Pau Farràs

doi:10.1002/cbic.202500589

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

Neville Murphy, Roberto González‐Gómez, Nivethitha Ashok, Enda O’Connell, Howard Fearnhead, William J. Tipping, Karen Faulds, Wenming Tong, Abhay Pandit, Róisín M. Dwyer, Duncan Graham, Pau Farràs^*

^*Corresponding author for this work

Pure And Applied Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e202500589
Number of pages	8
Journal	Chembiochem
Volume	26
Issue number	21
Early online date	7 Oct 2025
DOIs	https://doi.org/10.1002/cbic.202500589
Publication status	Published - 8 Nov 2025

Funding

This publication has emanated from research supported in part by a research grant from Research Ireland and is co\u2010funded under the European Regional Development Fund under grant number 13/RC/2073 P2. R.M.D. acknowledges funding support from the National Breast Cancer Research Institute grant number FY24001. D.G., K.F., and W.J.T. thank the University of Strathclyde for financial support and the EPSRC for providing the instrumentation via EP/N010914/1. The authors acknowledge the scientific and technical assistance of Dr. \u00C9adaoin Timmins in the use of SEM within the Anatomy Imaging and Microscopy Facility at the University of Galway.

Keywords

triple‐negative breast cancer
targeted delivery systems
metallacarboranes
hyaluronic acid
cobalt–bis(dicarbollide)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Murphy, N., González‐Gómez, R., Ashok, N., O’Connell, E., Fearnhead, H., Tipping, W. J., Faulds, K., Tong, W., Pandit, A., Dwyer, R. M., Graham, D., & Farràs, P. (2025). Functionalizing injectable hydrogels with cobalt‐based metallacarboranes for targeted delivery in triple‐negative breast cancer. Chembiochem, 26(21), Article e202500589. 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.",

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Murphy, N, González‐Gómez, R, Ashok, N, O’Connell, E, Fearnhead, H, Tipping, WJ , Faulds, K, Tong, W, Pandit, A, Dwyer, RM, Graham, D & Farràs, P 2025, 'Functionalizing injectable hydrogels with cobalt‐based metallacarboranes for targeted delivery in triple‐negative breast cancer', Chembiochem, vol. 26, no. 21, e202500589. https://doi.org/10.1002/cbic.202500589

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T1 - Functionalizing injectable hydrogels with cobalt‐based metallacarboranes for targeted delivery in triple‐negative breast cancer

AU - Murphy, Neville

AU - González‐Gómez, Roberto

AU - Ashok, Nivethitha

AU - O’Connell, Enda

AU - Fearnhead, Howard

AU - Tipping, William J.

AU - Faulds, Karen

AU - Tong, Wenming

AU - Pandit, Abhay

AU - Dwyer, Róisín M.

AU - Graham, Duncan

AU - Farràs, Pau

PY - 2025/11/8

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N2 - 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.

AB - 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.

KW - triple‐negative breast cancer

KW - targeted delivery systems

KW - metallacarboranes

KW - hyaluronic acid

KW - cobalt–bis(dicarbollide)

U2 - 10.1002/cbic.202500589

DO - 10.1002/cbic.202500589

M3 - Article

SN - 1439-4227

VL - 26

JO - Chembiochem

JF - Chembiochem

IS - 21

M1 - e202500589

ER -

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

Abstract

Funding

Keywords

UN SDGs

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