Nanotechnology-mediated delivery of resveratrol as promising strategy to improve therapeutic efficacy in triple negative breast cancer (TNBC): progress and promises

INTRODUCTION: Triple-negative breast cancer (TNBC) presents unique challenges in diagnosis and treatment. Resveratrol exhibits potential as a therapeutic intervention against TNBC by regulating various pathways such as the PI3K/AKT, RAS/RAF/ERK, PKCδ, and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to its poor biopharmaceutical characteristics and low bioavailability at the tumor site. Nanotechnology offers a promising approach to improving the biopharmaceutical characteristics of resveratrol to achieve clinical efficacy in different cancers. The small dimension (<200 nm) of nanotechnology-mediated drug delivery system is helpful to improve the bioavailability, internalization into the TNBC cell, ligand-specific targeted delivery of loaded resveratrol to tumor site including reversal of MDR (multi-drug resistance) condition. AREAS COVERED: This manuscript provides a comprehensive discussion on the structure-activity relationship (SAR), underlying anticancer mechanism, evidence of anticancer activity in in-vitro/in-vivo investigations, and the significance of nanotechnology-mediated delivery of resveratrol in TNBC. EXPERT OPINION: Advanced nano-formulations of resveratrol such as oxidized mesoporous carbon nanoparticles, macrophage-derived vesicular system, functionalized gold nanoparticles, etc. have increased the accumulation of loaded therapeutics at the tumor-site, and avoid off-target drug release. In conclusion, nano-resveratrol as a strategy may provide improved tumor-specific image-guided treatment options for TNBC utilizing theranostic approach.