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.

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