RESUMO
To address the limitations of norcantharidin (NCTD) in clinical applications, including restricted tumor accumulation and intense irritation, we have developed a new derivative of NCTD with (S)-1-benzyl-3-pyrrolidinol, which can be actively loaded into liposomes to achieve drug encapsulation and sustained release properties by using pH gradient loading technique. Cytotoxicity tests against cancer cell lines (Hepa 1-6 and 4 T1 cells) have demonstrated that this derivative exhibits comparable activity to NCTD in vitro. The NCTD derivative can be efficiently loaded into liposomes with high encapsulation efficiency (98.7%) and high drug loading (32.86%). Tolerability and antitumor efficacy studies showed that the liposomal NCTD derivative was well tolerated at intravenous injection doses of 3 folds higher than the parent drug solution, while significantly improved anticancer activity in vivo was achieved. This liposomal nanodrug could become a potent and safe NCTD formulation alternative for cancer therapy.