Preparation and anti-tumor effect in hepatocellular carcinoma treatment of AS1411 aptamer-targeted polyphyllin II-loaded PLGA nanoparticles

Polyphyllin II (PPII) have been proven to have significant anti-liver cancer activity, but its application is limited by poor solubility, low bioavailability and systemic toxicity caused by non-selectivity. To address above problem, PPII was encapsulated into the Poly (lactic-co-glycolic acid) (PLGA) by precipitation method (PPII-NPs) for hepatocellular carcinoma treatment. Subsequently, Box–Behnken design (BBD) with three variables-three levels (33) was utilized to optimize the PPII-NPs formulation. Under optimal conditions, the drug loading of nanoparticles reached 7.29 ± 0.08% and encapsulation efficiency was 80.98 ± 1.63%. Furthermore, aptamer AS1411 was adopted to enhance tumor-targeting ability of nanoparticles (Apt/PPII-NPs). The drug loading of Apt/PPII-NPs was 6.25 ± 0.26%, had spherical shape with a rough surface, the particle size of 252.3 ± 3.6 nm and showed good slow-release performance and stability. In vitro assays showed that the targeted modified nanoparticles had significant tumor selectivity and exerted efficient anti-tumor effect by inducing tumor cell apoptosis via mitochondrial apoptotic pathway and death‐receptor pathway. In vivo anti-tumor evaluation further demonstrated Apt/PPII-NPs not only effectively inhibited the growth of tumor, but also reduced PPII damage to normal tissues. In summary, this report strongly illustrated the advantages of targeted nanoparticle platform for providing a solution for the rational application of PPII and improving the therapeutic effect for hepatocellular carcinoma.