Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.

Breast cancer remains the most prevalent malignancy among women worldwide and a major cause of cancer-related mortality. Despite remarkable progress in molecularly targeted and immune-based therapies, therapeutic resistance, dose-limiting systemic toxicity, and inefficient drug delivery continue to hinder clinical outcomes, particularly in aggressive subtypes such as triple-negative breast cancer. Exosomes, naturally secreted nanosized vesicles, have emerged as a transformative platform owing to their biocompatibility, intrinsic targeting capability, and ability to transport diverse therapeutic cargos across biological barriers. Recent advances in exosome biology, engineering, and isolation technologies have reignited interest in their clinical exploitation as drug delivery systems. However, translation into clinical oncology remains in its early stages. This review provides a comprehensive overview of exosome-based drug delivery systems specifically within the context of breast cancer therapy, critically evaluating their sources, isolation techniques, cargo loading strategies, targeting mechanisms, and formulation considerations. It also examines preclinical findings demonstrating enhanced therapeutic efficacy and reduced off-target toxicity, alongside the limited yet growing number of clinical trials investigating exosome therapeutics in solid tumours. Importantly, the review identifies major gaps, including lack of standardized manufacturing protocols, incomplete pharmacokinetic understanding, and unresolved safety concerns, that currently impede clinical translation. By bridging molecular insights with translational perspectives, this work underscores the untapped potential of exosomes as next-generation drug carriers in breast cancer. It highlights the urgent need for harmonized methodologies, scalable production systems, and regulatory frameworks to enable their safe and effective integration into future cancer therapeutics.