Enhanced Anti-Tumor Efficacy of Paclitaxel Nanoparticles via Supramolecular Self-Assembly with Pterostilbene

Background: Paclitaxel (PTX), a taxane chemotherapy drug, is widely regarded as one of the most potent and clinically effective treatments for advanced and resistant cancers. However, paclitaxel's poor bioavailability is attributed to its unfavorable physicochemical properties, including low solubility and permeability. Nanosizing and multidrug combination strategies have emerged as key approaches to enhance the formulation of such compounds. Pterostilbene (PTE), a polyphenolic compound, possesses extensive anti-cancer properties and favorable hydrogen bond formation sites. In this study, PTE was employed to co-assemble with PTX to improve its physicochemical properties and enhance therapeutic efficacy. Methods: Paclitaxel-pterostilbene nanoparticles (PTX-PTE NPs) were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Results: PTX-PTE nanoparticles significantly improved the water solubility (7fold increase) and cytotoxicity of paclitaxel in tumor cells. The enhanced antitumor efficacy was achieved through P-gp and CDK1 protein downregulation, increased drug accumulation, and cell cycle inhibition. Conclusions: These improvements are attributed to the nanoparticles' amorphous structure and nanoscale properties. In addition, the combined use of PTX and PTE significantly enhanced the cytotoxicity against human non-small cell lung cancer A549 cells. PTX-PTE nanoparticles show promise for improving drug delivery and overcoming multidrug resistance in A549 cells.