Superoxide dismutase loaded biodegradable nanoparticles targeted with a follicle stimulating hormone peptide protect Sertoli cells from oxidative stress

Capsule:
Nanoparticles formulated with superoxide dismutase, an antioxidant enzyme, were conjugated to an FSH peptide. Conjugation increased Sertoli cell uptake and improved cell survival after oxidative stress.

Authors:
Devon C. Snow-Lisy, M.D., Edmund S. Sabanegh Jr., M.D., Mary K. Samplaski, M.D., Viola B. Morris, Ph.D., Vinod Labhasetwar, Ph.D.

Volume 101, Issue 2, Pages 560-567.e3, February 2014

Abstract:

Objective:
To evaluate targeted superoxide dismutase (SOD)–loaded biodegradable nanoparticles’ (NPs) ability to protect Sertoli cells from hydrogen peroxide (H2O2)-induced oxidative stress.

Design:
Cell culture controlled experimental study.

Setting:
Research laboratory.

Cells:
Mouse testis Sertoli cells (TM4).

Interventions:
Sertoli cells were exposed to 0–200 μg/mL plain media, unconjugated NPs, or FSH peptide–conjugated NPs for 2 or 24 hours to assess uptake. Next, Sertoli cells were exposed to 0–50 mmol H2O2 with 0–1 mg/mL unconjugated SOD-loaded NPs, FSH-conjugated SOD-loaded NPs, or equivalent units of SOD in solution as a control for 2–6 hours to assess influence on cell survival after oxidative stress.

Main Outcome Measure(s):
Cell viability, flow cytometry, and microscopy.

Result(s):
FSH peptide targeting improved uptake of NPs by Sertoli cells. FSH-conjugated SOD-NPs significantly protected Sertoli cells at 6 hours of H2O2−induced oxidative stress, with 100% survival with FSH-conjugated SOD-NPs compared with unconjugated SOD-NPs (45%) or SOD in solution (36%).

Conclusion(s):
Conjugation of NPs with FSH peptide improves cellular uptake and survival when SOD-loaded NPs are coincubated with Sertoli cells undergoing oxidative stress. This study represents a step toward developing NPs for the targeted treatment of testicular oxidative stress.

  • Devon Snow-Lisy

    Thank you Ed.
    We believe this study marks an important first step in the use of nanoparticle technology for the treatment of a variety of testicular disorders. We were especially encouraged by the ability of these nanoparticles to target Sertoli cells and to cross the blood-testis-barrier, which may have major implications for targeting in an in vivo model. We look forward to sharing our further work exploring nanoparticle targeted to the testis in an animal model. Thank you again for your interest!

  • Intriguing study out of the Cleveland Clinic. We have long sought to find a way to deliver medical treatments to the testicle but have been thwarted by the blood brain barrier. This study demonstrates the feasibility of utilizing nano particles for the delivery of antioxidants to the sertoli cells to protect them from oxidative stress. My hope is that this will result in future studies for directing hormonal or chemotherapeutic agents to the testicles for treatment of infertility or malignancy respectively. Well done.

Translate »