Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy

Sashwati Roy, Chandan K. Sen, Subhadip Ghatak, Natalia Higuita-Castro, Ravichand Palakurti, Nagajyothi Nalluri, Andrew Clark, Richard Stewart, Daniel Gallego-Perez, Daniel N. Prater, Savita Khanna*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.

Original languageEnglish
Article number102220
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume28
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • Diabetic peripheral neuropathy
  • Nanochannel electroporation
  • Tissue nanotransfection

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