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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. [ABSTRACT FROM AUTHOR]

A series of Pulsatilla saponin D (PSD) and α-hederin derivatives bearing NO donors were designed, synthesized and evaluated for anticancer activities in vitro and in vivo. Among them, most of the target compounds exhibited strong antiproliferative activities against the tested cancer cell lines, and derivatives 5a, 5b and 5c exhibited high levels of NO release. Furthermore, compound 5c treated with a dose of 15 mg kg−1 showed a more potent tumor inhibitory effect than that of Taxol (27.44% vs. 23.26%). In addition, compound 5c blocked the cell cycle at the S phase and induced cancer cell apoptosis in a concentration-dependent manner. [ABSTRACT FROM AUTHOR]