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

Polyphyllin II (PPII) has 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 the 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 the tumor-targeting ability of nanoparticles (Apt/PPII-NPs). The drug loading of Apt/PPII-NPs was 6.25 ± 0.26%, had a spherical shape with a rough surface, a 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 effects by inducing tumor cell apoptosis via the mitochondrial apoptotic pathway and death‐receptor pathway. In vivo, anti-tumor evaluation further demonstrated Apt/PPII-NPs not only effectively inhibited the growth of tumors, but also reduced PPII damage to normal tissues. In summary, this report strongly illustrated the advantages of a targeted nanoparticle platform for providing a solution for the rational application of PPII and improving the therapeutic effect of hepatocellular carcinoma.