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Intratesticular Peptidyl Prolyl Isomerase 1 Protein Delivery Using Cationic Lipid-Coated Fibroin Nanoparticle Complexes Rescues Male Infertility in Mice

Cited 9 time in Web of Science Cited 10 time in Scopus
Authors

Kim, Woo Jin; Kim, Bong Soo; Kim, Hyun Jung; Cho, Young Dan; Shin, Hye Lim; Yoon, Hee In; Lee, Yun Sil; Baek, Jeong-Hwa; Woo, Kyung Mi; Ryoo, Hyun-Mo

Issue Date
2020-10
Publisher
American Chemical Society
Citation
ACS Nano, Vol.14 No.10, pp.13217-13231
Abstract
Male infertility is a multifactorial condition. Unexplained male infertility is often caused by spermatogenesis dysfunction. Knockout of Pin1, an important regulator of cell proliferation and differentiation, produces male infertility phenotypes such as testicular immaturity and azoospermia with spermatogonia depletion and blood-testis barrier (BTB) dysfunction. Gene therapy has been clinically considered for the treatment of male infertility, but it is not preferred because of the risks of adverse effects in germ cells. Direct intracellular protein delivery using nanoparticles is considered an effective alternative to gene therapy; however, in vivo testicular protein delivery remains a pressing challenge. Here, we investigated the direct intracellular protein delivery strategy using a fibroin nanoparticle-encapsulated cationic lipid complex (Fibroplex) to restore intratesticular PIN1. Local intratesticular delivery of PIN1 via Fibroplex in Pin1 knockout testes produced fertile mice, achieving recovery from the infertile phenotypes. Mechanistically, PIN1-loaded Fibroplex was successfully delivered into testicular cells, including spermatogonial cells and Sertoli cells, and the sustained release of PIN1 restored the gene expression required for the proliferation of spermatogonial cells and BTB integrity in Pin1 knockout testes. Collectively, testicular PIN1 protein delivery using Fibroplex might be an effective strategy for treating male infertility.
ISSN
1936-0851
URI
https://hdl.handle.net/10371/200485
DOI
https://doi.org/10.1021/acsnano.0c04936
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Cho, Young-Dan조영단
(기금)조교수
  • School of Dentistry
  • Department of Dentistry
Research Area Alveolar bone regeneration, Dental implant surface modification, Periomics

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