Tumor neovasculature-targeted cationic PEGylated liposomes of gambogic acid for the treatment of triple-negative breast cancer.

Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor aqueous solubility. In the present study, positively charged PEGylated liposomal formulation of GA (GAL) was developed for parenteral delivery for the treatment of triple-negative breast cancer (TNBC). The GAL was formulated with a particle size of 107.3 ± 10.6 nm with +32 mV zeta potential. GAL showed very minimal release of GA over 24 h period confirming the non-leakiness and stability of liposomes. In vitro cytotoxicity assays showed similar cell killing with GA and GAL against MDA-MB-231 cells but significantly higher inhibition of HUVEC growth was observed with GAL. Furthermore, GAL significantly (p < 0.05) inhibited the MDA-MB-231 orthotopic xenograft tumor growth with >50% reduction of tumor volume and reduction in tumor weight by 1.7-fold and 2.2-fold when compared to GA and controls, respectively. Results of western blot analysis indicated that GAL significantly suppressed the expression of apoptotic markers, bcl2, cyclinD1, survivin and microvessel density marker-CD31 and increased the expression of p53 and Bax compared to GA and control. Collectively, these data provide further support for the potential applications of cationic GAL in its intravenous delivery and its significant role in inhibiting angiogenesis against TNBC.