Evaluation of novel paclitaxel-loaded NO-donating polymeric micelles for an improved therapy for gastroenteric tumor

Abstract

This study reports the design and synthesis of NO-donating polymer to generate biodegradable polymeric micelle containing paclitaxel (NO/PTX) as a nanomedicine delivery system aimed to enhance the solubility and anti-cancer activity of paclitaxel (PTX). NO/PTX showed greater NO-releasing performance than nitroglycerin, displaying excellent tolerance in KM mice, and exhibited a two-fold stronger antiproliferative activity than PTX in vitro against HCT116, SW480, and SGC-7901 cell lines. In vivo tumor growth inhibition assay results indicated that NO/PTX displayed lightly stronger activities against tumor growth than PTX at a dose of 10 mg kg⁻¹, while the anti-tumor effect of NO/PTX was significantly improved than that of PTX and Genexol®-PM groups at a dose of 15 mg kg⁻¹ (the inhibition rate: 67% vs. 53% and 41%). In addition, NO/PTX showed an improved area under the plasma concentration-time curve and drug deposition in tumors in comparison to PTX. Wound healing assay and western blot analysis of EMT-related markers suggested that NO/PTX could inhibit the potential of HCT116 migration. Western blot analysis also demonstrated that NO/PTX dampened efflux activity of P-gp and up-regulated apoptosis-related proteins. Overall, these promising results suggested that the synergism between PTX and NO-donating micelles could contribute to the potent anti-cancer activity of NO/PTX.