Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin

SIMPLE SUMMARY: The aim of our study is to use E-selectin-binding peptide (ESBP) to actively recognize E-selectin, so allowing a drug delivery system to actively recognize the cells and inhibit ovarian cancer cells by targeting adhesion molecules of E-selectin. A drug-loaded nanoparticle with a special structure was designed as the drug carrier. Based on the fact that tumors often occur together with inflammation, the drug could be delivered to and more concentrated in ovarian tumor sites as well as tumor-associated inflammatory cells by using this drug-delivery system targeting selectins. Through recognition and binding with E-selectin in ovarian cancer cells and utilizing the steric hindrance effect of macromolecules that nanoparticles possess, paclitaxel was delivered and released, thus inducing ovarian cancer cell apoptosis and cell migration and decreasing myeloid-derived suppressor cells related to drug-resistance in a mouse model. It also had higher drug efficacy, extended the survival of tumor-bearing mice and had relatively lower in vivo toxicity than paclitaxel treatment. All results in this study provided potent proof of its potential to be applied to clinical use. ABSTRACT: Objective: The aim is to use E-selectin-binding peptide (ESBP) to actively recognize E-selectin, so allowing a drug delivery system to actively recognize the cells and inhibit the tumor growth of ovarian cancer by targeting adhesion molecules of E-selectin. An ovarian-cancer-directed drug delivery system was designed based on the high affinity of E-selectin-binding peptide (ESBP) to E-selectin. The effects and mechanisms of ESBP-bovine serum albumin (BSA) polymerized nanoparticles were investigated. Methods: BSA polymerized nanoparticles (BSANPs) and ESBP-BSANPs-paclitaxel (PTX) were prepared and their characteristics were measured. The in vitro targetability and cytotoxicity of ESBP-BSANPs-PTX were evaluated through in vitro drug uptake and MTT experiments. The mechanisms of ESBP-BSANPs-PTX were investigated via apoptosis, wound healing and immunohistochemistry assays. The in vivo targeting properties and drug effects were observed in a mouse tumor-bearing model. Results: In vitro experiments revealed an increase in the uptake of ESBP-BSANPs-FITC. The cytotoxicity of ESBP-BSANPs-PTX in A2780/CP70, HUVEC, RAW264.7 and ID8 cells was higher than that of PTX alone. ESBP-BSANPs-PTX increased cell apoptosis in a dose-dependent manner and exhibited a greater ability to inhibit cell migration than BSANPs-PTX. In vivo experiments demonstrated the targetability and good effects of ESBP-BSANPs. Conclusions: ESBP-BSANPs-PTX improve PTX targetability, provide tumor-specific and potent therapeutic activities, and show promise for the development of agents in preclinical epithelial ovarian cancer.