title: Superoxide dismutase-loaded biodegradable nanoparticles targeted with a follicle-stimulating hormone peptide protect Sertoli cells from oxidative stress.
abstract: OBJECTIVE
  To evaluate targeted superoxide dismutase (SOD)-loaded biodegradable nanoparticles' (NPs) ability to protect Sertoli cells from hydrogen peroxide (H2O2)-induced oxidative stress.
  
  
  METHODS
  Cell culture controlled experimental study.
  
  
  METHODS
  Research laboratory.
  Mouse testis Sertoli cells (TM4).
  
  
  METHODS
  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.
  
  
  METHODS
  Cell viability, flow cytometry, and microscopy.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: snowlid@ccf.org.
authors.forename: Devon C
authors.initials: DC
authors.lastname: Snow-Lisy
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Sabanegh
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Samplaski
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Viola B
authors.initials: VB
authors.lastname: Morris
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Vinod
authors.initials: V
authors.lastname: Labhasetwar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D012708:Sertoli Cells / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000975:Antioxidants; D005640:Follicle Stimulating Hormone; D013482:Superoxide Dismutase
keywords: Drug delivery; antioxidant; encapsulation; targeting; testis