Targeted delivery aspects of proanthocyanidins in breast cancer treatment: from discovery to development

Proanthocyanidins (PACs), a group of naturally occurring polyphenolic compounds found in a variety of fruits, vegetables, nuts, and seeds, have shown remarkable potential in the treatment of breast cancer (BC). These bioactive molecules exhibit antioxidant, anti-inflammatory, and anticancer properties by triggering apoptosis, halting cell cycle progression, and suppressing angiogenesis and metastasis. PACs further contribute to immune modulation and regulate critical signaling pathways like PI3K/Akt and MAPK, which are closely linked to cancer development. When combined with other bioactive agents, PACs have been shown to enhance therapeutic efficacy. Advanced delivery approaches, including PAC conjugation with targeting molecules and natural biopolymers, such as proteins and polysaccharides, are being explored to improve their effectiveness. Despite increasing interest in the anticancer potential of PACs, a comprehensive analysis of their molecular mechanisms, synergistic effects, and formulation strategies specifically in the context of breast cancer is lacking. This review aims to fill that gap by compiling and critically evaluating current preclinical evidence, novel delivery approaches, and safety considerations related to PACs in breast cancer therapy. Although preclinical investigations provide encouraging evidence, the availability of clinical studies remains scarce, emphasizing the need for further exploration. The discussion also encompasses the safety profile and possible toxicological concerns of PACs, underlining their therapeutic potential and existing challenges. Despite current limitations, PACs hold promise for BC treatment, with future research aiming to refine their clinical applicability.