Phage display identified Sertoli and Leydig cell homing peptides for drug delivery to testis — ASN Events

Phage display identified Sertoli and Leydig cell homing peptides for drug delivery to testis (#267)

Yugandhara Jirwankar 1 , Akanksha Nair 1 , Vikas Dighe 1
  1. National Centre for Preclinical Reproductive and Genetic Toxicology, ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, Maharashtra, India

Zip codes are the molecular signatures present on the specific cells, tissues, and organs. These Zip codes can be exploited by homing peptides to deliver the drugs cell types, tissue, and organs. In testis, testosterone is produced by Leydig cells, and Sertoli cells provide sustenance to developing spermatids. Hence, Sertoli and Leydig cells are vital targets for the treatment of infertility or contraceptive drug delivery.

In this study, phages with Sertoli and Leydig cell homing peptides were selected from a 12-mer phage display library through in-vitro followed by in-vivo bio-panning. The peptide sequences displayed by the selected phages were determined through Illumina sequencing. Peptides homing to Sertoli and Leydig cells are found to have unique sequences. The FITC labeled Sertoli cell homing peptides (SCHPs) and Leydig cell homing peptides (LCHPs) show selective uptake by mouse Sertoli and Leydig cells, respectively. However, both Cy5.5 labeled SCHPs and LCHPs can target testis in the animal model. CD spectroscopy analyses suggest these peptides forms random coil structure in water, but helix and beta turns appear at higher concentrations of TFE with cell membrane-like environments. Further, the FITC and Cy5.5 labeled peptides are stable for a longer time in blood plasma than the unlabelled peptides. The findings suggest the potential use of these peptides as a carrier to make peptide drug conjugates (PDCs) for targeted drug delivery to the testis.

  1. Ruoslahti, E., Duza, T. & Zhang, L. Vascular homing peptides with cell-penetrating properties. Curr. Pharm. Des. (2005) doi:10.2174/138161205774580787.
  2. Snow-Lisy, D. C., Samplaski, M. K., Labhasetwar, V. & Sabanegh, E. S. Drug delivery to the testis: current status and potential pathways for the development of novel therapeutics. Drug Deliv. Transl. Res. 1, 351 (2011).
  3. Jirwankar, Y. & Dighe, V. Identification and validation of Sertoli cell homing peptides as molecular steering for testis targeted drug delivery. J. Drug Target. 1–12 (2023) doi:10.1080/1061186X.2022.2164007.
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