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

**Authors:** 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

PMC · DOI: 10.1002/cbic.202500589 · Chembiochem · 2025-10-07

## TL;DR

This study creates a hydrogel that delivers cobalt-based compounds to treat triple-negative breast cancer while keeping their cancer-killing power intact.

## Contribution

A biocompatible hydrogel system is developed to noncovalently incorporate cobalt metallacarborane for targeted cancer therapy.

## Key findings

- HA-Lys hydrogel retains CoSAN's cytotoxic activity in triple-negative breast cancer cells.
- EDX and NMR confirm successful and homogeneous integration of CoSAN into the hydrogel.
- The hydrogel shows pH-dependent sustained release of CoSAN over 24 hours.

## 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.

This study reports a biocompatible HA–lysine hydrogel loaded with cobalt metallacarborane (CoSAN) for targeted release into triple‐negative breast cancer cells. The system maintains CoSAN cytotoxicity, as confirmed by cell assays and imaging, representing an attractive approach toward a localised TNBC treatment.© 2025 WILEY‐VCH GmbH

## Linked entities

- **Chemicals:** CoSAN (PubChem CID 402), lysine (PubChem CID 866)
- **Diseases:** triple-negative breast cancer (MONDO:0005494)

## Full-text entities

- **Diseases:** cytotoxic (MESH:D064420), cancer (MESH:D009369), Breast Cancer (MESH:D001943)
- **Chemicals:** Cobalt (MESH:D003035), Lys (MESH:D008239), HA-Lys (-), HA (MESH:D006820), CoSAN (MESH:C000726368)
- **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), MDA-MB-231 triple-negative breast cancer — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_B5N7)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12596922/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12596922/full.md

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Source: https://tomesphere.com/paper/PMC12596922