Estrone-targeted PEGylated Liposomal Nanoparticles for Cisplatin (DDP) Delivery in Cervical Cancer

Cisplatin (DDP), a first-line chemo-drug for cervical cancer therapy, has limited the clinical use due to its high-dose administration and strong side effects. In this study, estrone-targeted PEGylated Liposomal DDP (ES-SSL-DDP) was prepared by thin-film hydration method and characterized. ES-SSL-DDP presented a spherical structure, with a particle size of about 97.3 nm, a surface charge of -19 mV and a high encapsulation efficiency of 47.7%. ES-SSL-DDP showed higher stability with a lower leakage rate less than 10% at 4°C. In vitro cellular uptake and internalization mechanisms in HeLa cells showed that ES-SSL-DDP had a stronger cellular uptake which was mainly via caveolin-mediated endocytosis. In vivo targeting evaluation demonstrated ES-SSL-DDP could specifically accumulated into the tumor site of HeLa-bearing mice. Cytotoxicity test on HeLa cells demonstrated the stronger cytotoxic activity of ES-SSL-DDP by MTT assay. In vivo anti-tumor efficacy of ES-SSL-DDP in HeLa tumor-bearing mice exhibited the most effective tumor inhibition. Pharmacokinetics and biodistribution of ES-SSL-DDP presented an improved metabolic behavior of the DDP. The acute toxicity demonstrated that ES-SSL-DDP could increase the LD₅₀ and reduce the myelosuppression in healthy ICR mice. ES-SSL-DDP could be a novel promising chemo-formulation for cervical cancer in the future clinic.