Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin
Bowen Yang1,2, Shanmei Yin3, Zishuo Zhou3
1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
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.
Insights
E-selectin-binding peptide (ESBP) conjugated nanoparticles target ovarian cancer cells, enhancing drug delivery and inhibiting tumor growth. This targeted approach shows promise for preclinical epithelial ovarian cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Epithelial ovarian cancer (EOC) remains a significant health challenge with limited effective targeted therapies.
- Targeting adhesion molecules like E-selectin offers a potential strategy for specific cancer cell recognition and drug delivery.
- Developing novel drug delivery systems (DDS) is crucial for improving therapeutic efficacy and reducing side effects.
Purpose of the Study:
- To design and evaluate an ovarian cancer-directed drug delivery system utilizing E-selectin-binding peptide (ESBP).
- To investigate the targeting capabilities and therapeutic effects of ESBP-conjugated bovine serum albumin (BSA) polymerized nanoparticles (ESBP-BSANPs) loaded with paclitaxel (PTX).
- To elucidate the mechanisms underlying the anti-tumor activity of ESBP-BSANPs-PTX in both in vitro and in vivo models.
Main Methods:
- Preparation and characterization of BSA polymerized nanoparticles (BSANPs) and ESBP-BSANPs loaded with paclitaxel (PTX).
- In vitro assessment of nanoparticle targetability (using FITC-labeled nanoparticles) and cytotoxicity (MTT assay) in ovarian cancer cells and relevant cell lines.
- In vivo evaluation of targeting properties and anti-tumor efficacy in a mouse model of ovarian cancer.
Main Results:
- ESBP-BSANPs demonstrated enhanced in vitro cellular uptake compared to control nanoparticles.
- ESBP-BSANPs-PTX exhibited significantly higher cytotoxicity against ovarian cancer cells than PTX alone.
- In vivo studies confirmed the targeting ability and effective tumor inhibition by ESBP-BSANPs, with increased apoptosis and reduced cell migration.
Conclusions:
- ESBP-BSANPs-PTX effectively improve paclitaxel targetability, delivering potent, tumor-specific therapeutic activity.
- The developed drug delivery system shows significant promise for preclinical applications in epithelial ovarian cancer treatment.
- Targeting E-selectin with ESBP-functionalized nanoparticles represents a viable strategy for enhancing ovarian cancer therapy.
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