Hydroxyapatite-Based Targeted Drug Delivery Systems for HER2-Positive Breast Cancer: The Role of Trastuzumab and Folic Acid Functionalization

Worldwide, breast cancer continues to be one of the most frequently diagnosed malignancies and continues to pose a significant challenge in cancer therapy. Despite the significant improvement in patient survival that HER2-targeted therapies, such as trastuzumab, have achieved, their therapeutic efficacy remains restricted by challenges such as cardiotoxicity, acquired resistance, limited tumor accumulation, and off-target effects. Recent developments in drug delivery systems have concentrated on the enhancement of treatment outcomes by utilizing targeted delivery strategies and controlled drug release. Among various carrier materials, hydroxyapatite (HAp) has attracted considerable attention due to its excellent biocompatibility, bioactivity, porous structure, high drug-loading capacity, and ease of surface functionalization. These characteristics make HAp a promising candidate for the development of advanced drug delivery platforms capable of enhancing therapeutic efficiency while minimizing systemic side effects. Furthermore, surface modification with targeting ligands such as folic acid offers additional opportunities for improving local cellular recognition and targeted drug delivery. This review summarizes current developments in hydroxyapatite-based drug delivery systems for breast cancer therapy, with particular emphasis on trastuzumab delivery, folic acid-mediated targeting approaches, and hydroxyapatite microsphere technologies. Recent studies investigating HAp-based carriers, targeted delivery systems, and multifunctional therapeutic platforms are discussed, together with their advantages, limitations, and clinical potential. In addition, the role of microsphere-based delivery systems in achieving sustained drug release and enhanced therapeutic performance is highlighted. Current literature demonstrates the potential of hydroxyapatite carriers for the delivery of various therapeutic agents; however, studies integrating trastuzumab delivery, folic acid-mediated targeting, and hydroxyapatite microspheres within a single platform remain limited. This gap highlights the need for multifunctional carrier systems capable of combining controlled release with selective cellular recognition and targeted delivery. The available literature suggests that hydroxyapatite microspheres may provide a versatile platform for HER2-targeted therapy, with trastuzumab potentially incorporated as a therapeutic cargo or used as a surface-bound targeting ligand. These approaches differ in their intended functions and may enable controlled drug release and HER2-mediated targeting, respectively.