Tailoring Carrier-Free Nanoparticles based on Natural Small Molecule Assembly for Synergistic Anti-tumor Efficacy

Interfacial modular assemblies of versatile polyphenols have attracted widespread interest in surface and materials engineering. In this study, natural polyphenol (tannic acid, TA) and nobiletin (NOB) can directly form binary carrier-free spherical nanoparticles (NT NPs) through synergistically driven by a variety of interactions (such as hydrogen bonding, oxidative reactions, etc.). The synthesis involves polyphenolic deposition on hydrophobic NOB nanoaggregates, followed by in situ oxidative self-polymerization. Interestingly, the assembled NT NPs exhibit controllable and dynamic changes in particle size during the initial stage. Ultimately, uniform and spherical NT NPs appear stable, with high loading capability, enabling incorporated NOB to preserve their function. Furthermore, in vitro evaluations demonstrate that the rational combination of polyphenol module and NOB can induce apoptosis and inhibit tumor metastasis for both lung cancer H1299 and human fibrosarcoma HT1080 cell lines. Notably, the optimized NT48 NPs were then verified in vivo experiments to achieve a promising synergistic anti-tumor efficacy. These findings not only provide new opportunities for the streamlined and sensible engineering of future polyphenol-based biomaterials, but also open up new prospects for the design of small-molecule nature phytochemicals.