Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy

• Published in: Materials today bio Vol. 19; p. 100575
• Main Authors: Fan, Xinli, Zhao, Xiaoran, Xu, Jianfei, Wang, Jing, Wang, Qian, Tang, Xinjing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2023; Elsevier
• Subjects: Androgenetic alopecia; Full Length; Gas6; Gene therapy; Hair reproduction; Non-viral vector; Transdermal delivery; Transdermal delivery; Non-viral vector; Hair reproduction; Gene therapy; Gas6; Androgenetic alopecia
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2023.100575

Androgenetic alopecia is an androgen-dependent skin disorder that commonly affects hair follicle growth and hair loss. Gene therapy that can promote the proliferation and survival of hair follicle cells can be a potential choice for its cure. While transdermal application of therapeutic functional nucleic acids across the stratum corneum is quite difficult. Here, we first develop a transdermal agent for functional nucleic acid delivery using Triton X-100-modified low molecular weight polyethyleneimine (PEI-Triton-N, N ​= ​6 or 8). In vitro cell experiments demonstrate that the PEI-Triton-N conjugates can stably encapsulate and efficiently deliver plasmid DNA to hard-to-transfect keratinocyte HaCaT cells. Further mouse model studies show that PEI-Triton-6 can encapsulate and deliver growth arrest-specific protein 6 (Gas6) plasmid through transdermal administration. The transfected Gas6 prolongs the anagen status, inhibits the apoptosis of hair follicle cells, and further promotes the proliferation and differentiation of hair follicle cells. The PEI-Triton-6/pDNAGas6 complexes can obviously alleviate hair loss in androgenetic alopecia mice and provides a promising strategy for gene therapy via transdermal administration. PEI-Triton-6 conjugate can effectively encapsulate and deliver pDNAGas6 across epidermal barriers. The transdermal administration of PEI-Triton-6/pDNAGas6 complexes alleviates androgenetic alopecia in mice and provides a promising transdermal gene therapy for skin diseases. [Display omitted]