Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy

Abstract

Objective: Traditional chemotherapy drugs have an obvious drawback of nonspecific biodistribution in treating ovarian cancer. Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor which is mainly expressed in reproductive system, is an important drug target in developing novel therapeutics.

Methods: Using a polypeptide of follicle-stimulating hormone (named as FSHP), a conjugated nanoparticle, FSHP-NP was developed to target FSHR in lymphatic metastasis of ovarian cancer. FSHP-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. A paclitaxel (PTX)-loaded FSHP-NP (FSHP-NP-PTX) was further developed and its anti-tumor effect was determined in vivo and in vitro.

Results: Taking NuTu-19 cells as an example, FSHP-NP-PTX displayed significantly stronger anti-cell proliferative and anti-tumor effects in a dose- and time-dependent manner when compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) in vitro. In vivo examinations showed that the size and weight of the lymph nodes were reduced in the FSHP-NP-PTX group.

Conclusion: FSHR as a novel therapeutic target in ovarian cancer and delivery of PTX via conjugated nanoparticle (FSHP-NP) might represent a new therapeutic approach in ovarian cancer.

Keywords: Follicle stimulating hormone receptor (FSHR); Follicle-stimulating hormone polypeptide (FSHP); Lymphatic metastasis; Ovarian carcinoma; Paclitaxel (PTX).