Sodium oleate functionalized simvastatin liposomes: boosting endosomal escape and anticancer efficacy in triple negative breast cancer.

Background and purpose: Due to delivery obstacles, Simvastatin, a potential anticancer agent, faces clinical limitations. This study aimed to enhance simvastatin delivery and efficacy against triple-negative breast cancer (TNBC) by developing liposomes modified with sodium oleate (NaOL) to improve endosomal escape.

Experimental approach: Simvastatin was encapsulated in 1,2-dimyristoyl-sn-glycero-3-phosphocholine/cholesterol liposomes through thin film hydration. Liposomes with poly(lactic-co-glycolic acid) (PLGA), individually modified with NaOL and PLGA, served as a control endosomal escape enhancer. Formulations were characterized for size, charge, and encapsulation efficiency. Endosomal escape was quantified through subcellular colocalization analysis using confocal microscopy, and anticancer activity was assessed by evaluating cytotoxicity against 4T1 TNBC cells, followed by measurements of intracellular reactive oxygen species (ROS) and DNA damage.

Findings/results: Unmodified liposomes had a size of 115.2 ± 7.94 nm, a zeta potential of -9.67 ± 3.01 mV, and an encapsulation efficiency of 78.93% ± 6.72. NaOL-modified liposomes had a size of 119 ± 9.37 nm, a zeta potential of -31.05 ± 2.38 mV, and an encapsulation efficiency of 84.96% ± 2.51. While PLGA-modified liposomes had a size of 151.1 ± 7.35 nm, zeta potential of -18.68 ± 1.41 mV, and encapsulation efficiency of 83.63% ± 5.56. Importantly, NaOL-liposomes exhibited lower IC₅₀ values, improved endosomal escape, and enhanced anticancer activity compared to unmodified liposomes.

Conclusion and implications: Surface modification with NaOL is a promising strategy to enhance the anticancer efficacy of simvastatin liposomes against TNBC through improved endosomal escape. These encouraging in-vitro findings warrant further in-vivo investigations into the potential for NaOL-modified liposomes to improve TNBC patient outcomes.