755 PEPTIDE AMPHIPHILE NANOFIBER DELIVERY OF SONIC HEDGEHOG PROTEIN TO REDUCE SMOOTH MUSCLE APOPTOSIS IN THE PENIS AFTER CAVERNOUS NERVE RESECTION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 2011755 PEPTIDE AMPHIPHILE NANOFIBER DELIVERY OF SONIC HEDGEHOG PROTEIN TO REDUCE SMOOTH MUSCLE APOPTOSIS IN THE PENIS AFTER CAVERNOUS NERVE RESECTION Christopher Bond, Nicholas Angeloni, Daniel Harrington, Samuel Stupp, Kevin McKenna, and Carol Podlasek Christopher BondChristopher Bond Chicago, IL More articles by this author , Nicholas AngeloniNicholas Angeloni Chicago, IL More articles by this author , Daniel HarringtonDaniel Harrington Houston, TX More articles by this author , Samuel StuppSamuel Stupp Chicago, IL More articles by this author , Kevin McKennaKevin McKenna Chicago, IL More articles by this author , and Carol PodlasekCarol Podlasek Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1780AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) is a serious medical condition that affects 16–82% of prostate cancer patients treated by radical prostatectomy and current treatments are ineffective in 50–60% of prostatectomy patients. The reduced efficacy of treatments makes novel therapeutic approaches to treat ED essential. The secreted protein Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle and apoptosis that is decreased in cavernous nerve (CN) injury and diabetic ED models. Past studies using Affi-Gel beads have shown SHH protein to be effective in suppressing apoptosis caused by CN injury. In this study, we develop a novel peptide amphiphile (PA) nanofiber as a delivery vehicle for SHH protein to the penis to prevent apoptosis and ED, with the goal in mind to translate this methodology to the clinic to treat ED patients. METHODS Adult Sprague Dawley rats (n=50) were used to optimize PA injection in vivo. PA with SHH protein (n=16) or BSA (control, n=14) was injected into adult rats that under went bilateral CN cut. Rats were sacrificed at 2, 4 and 7 days. Alexa Fluor labeled SHH protein was used to determine the target of SHH signaling (n=3). Apoptotic and proliferation indices were quantified by counting and semi-quantitative immunohistochemical analysis for SHH protein was performed. RESULTS SHH-PA caused a 25% and 16% reduction in apoptosis at 4 and 7 days after CN injury and a 9.3% and 19% increase in SHH protein at 4 and 7 days after CN injury. Proliferation was increased 33%, 27% and 24% at 2, 4 and 7 days, respectively. In vitro, 73% of SHH protein diffused from PA within 6 days. Labeled SHH was observed in smooth muscle. CONCLUSIONS PA technology is effective in delivering SHH protein to the penis. SHH is effective in suppressing CN injury-induced apoptosis. These results show substantial translational potential of this methodology to prostatectomy and diabetic patients to prevent apoptosis and corpora cavernosal remodeling and show that only a short duration of SHH treatment is required to impact the apoptotic and proliferation indices. This methodology may also be useful as a delivery tool for other proteins of interest to the corpora cavernosa. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e304 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Bond Chicago, IL More articles by this author Nicholas Angeloni Chicago, IL More articles by this author Daniel Harrington Houston, TX More articles by this author Samuel Stupp Chicago, IL More articles by this author Kevin McKenna Chicago, IL More articles by this author Carol Podlasek Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...