pH-Sensitive hydrogels for breast cancer therapy: Targeted drug delivery and controlled release approaches

Breast cancer remains a major global health concern, necessitating advanced therapeutic strategies to overcome the limitations of conventional systemic treatments. pH-responsive hydrogels have emerged as promising platforms for targeted drug delivery and controlled release, exploiting the acidic microenvironment characteristic of breast tumors. These smart biomaterials can undergo physicochemical changes in response to pH variations, allowing for site-specific release of therapeutic agents. This review explores the unique pH gradients within breast tumor tissues and intracellular compartments, and how they can be harnessed for hydrogel-based drug delivery. We detail the design strategies of pH-sensitive hydrogels, including functional group selection, crosslinking mechanisms, and dual/multi-responsive capabilities. Furthermore, we highlight recent advances in their application for localized chemotherapy, combination therapies, gene/siRNA delivery, and post-surgical implantable systems. Despite their potential, challenges such as tumor heterogeneity and scalability remain. This review also discusses future directions, including personalized hydrogel systems and integration with theranostic tools, paving the way for precision breast cancer therapy.