Natural compound-nanoparticle therapies for breast cancer: A review from 2018-2025.

[BACKGROUND] Breast cancer (BC) poses significant global challenges due to drug resistance, toxicity, and subtype heterogeneity. Some plant derived natural compounds show multi-target anticancer potential but suffer from poor bioavailability and rapid metabolism. To overcome these intrinsic pharmaceutical limitations, nanotechnology-based delivery strategies have been extensively explored.

[PURPOSE] This review evaluates the literature from 2018 to 2024 to assess how nanotechnology enables clinical translation of natural compounds by enhancing delivery, overcoming biological barriers, and addressing translational challenges in BC therapy.

[METHODS] We conducted a comprehensive and critical analysis of the literature concerning the pharmacology of natural compounds with proven anti-BC activity, the design of various nanocarriers (e.g., liposomes, polymeric NPs), targeting approaches (e.g., EPR effect, ligand conjugation), and innovative solutions for tumor microenvironment barriers, biodistribution, and scalability.

[RESULTS] The analysis of preclinical studies demonstrates that nanoformulations improve natural compound efficacy 2-5-fold. Key advancements include a marked enhancement in solubility and bioavailability, exemplified by an increase in curcumin bioavailability from <1 % to over 90 %, and significantly higher tumor accumulation, as seen with HER2-targeted nanoparticles showing 3-fold higher uptake. The development of stimuli-responsive systems has enabled pH- and redox-triggered drug release, while strategies like PEGylation have successfully extended circulation half-life. Critical translational barriers were identified, including protein corona effects, which can reduce targeting efficiency by 30-50 %, and immune clearance; these are being actively addressed through biomimetic coatings and AI-optimized designs. Clinically, liposomal paclitaxel has reached Phase III trials, and nano-curcumin has shown promise in Phase II studies.

[CONCLUSION] This review concludes that natural compound-NPs therapies constitute a transformative and synergistic strategy for BC therapy. To realize their full clinical potential, interdisciplinary collaboration is essential for optimizing manufacturing processes and validating predictive biomarkers. Future research efforts must focus on the rational design of intelligent, multi-responsive nanosystems that are specifically tailored to the molecular subtypes of BC. Ultimately, establishing robust regulatory frameworks and scalable manufacturing pathways is imperative to successfully bridge the gap between promising preclinical results and tangible clinical benefits for patients.