TY - JOUR
T1 - Endoplasmic Reticulum-Targeting Highly Branched Poly(β-amino ester)s for Skin Gene Delivery
AU - Wang, Chenfei
AU - He, Wei
AU - Guo, Rui
AU - Pan, Chaolan
AU - Yong, Haiyang
AU - Bo, Tao
AU - Zhao, Yitong
AU - Li, Zhili
AU - Wang, Feifei
AU - Xu, Weiyi
AU - Yao, Dingjin
AU - Zhang, Si
AU - Li, Ming
AU - Zhou, Dezhong
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/11/4
Y1 - 2024/11/4
N2 - Gene therapy has emerged as a promising strategy for treating various hereditary cutaneous disorders. However, the entrapment of nucleic acids in endosomes is a significant hurdle. Here we synthesized endoplasmic reticulum (ER)-targeting highly branched poly(β-amino ester)s (ER-HPAEs) and investigated their potential for skin gene delivery. The incorporation of methyl-benzenesulfonamide (NMS) moieties endowed ER-HPAEs with a strong ER-targeting ability, allowing ER-HPAE/DNA polyplexes to bypass the conventional endosomal pathway and facilitate nuclear internalization. The optimized ER-HPAEs exhibited high transfection efficiency and biocompatibility across multiple cell types, surpassing the performance of Lipofectamine 3000 (Lipo3000). Intriguingly, the ER-HPAEs can effectively deliver plasmids to mediate high-levels of transglutaminase 1 (TGM1), membrane-bound transcription factor peptidase site 1 (MBTPS1), and collagen type VII alpha 1 chain (COL7A1) expression both in vitro and in vivo. This study establishes a strategy for synthesizing HPAEs with ER-targeting ability and identifies potential candidates for skin gene delivery.
AB - Gene therapy has emerged as a promising strategy for treating various hereditary cutaneous disorders. However, the entrapment of nucleic acids in endosomes is a significant hurdle. Here we synthesized endoplasmic reticulum (ER)-targeting highly branched poly(β-amino ester)s (ER-HPAEs) and investigated their potential for skin gene delivery. The incorporation of methyl-benzenesulfonamide (NMS) moieties endowed ER-HPAEs with a strong ER-targeting ability, allowing ER-HPAE/DNA polyplexes to bypass the conventional endosomal pathway and facilitate nuclear internalization. The optimized ER-HPAEs exhibited high transfection efficiency and biocompatibility across multiple cell types, surpassing the performance of Lipofectamine 3000 (Lipo3000). Intriguingly, the ER-HPAEs can effectively deliver plasmids to mediate high-levels of transglutaminase 1 (TGM1), membrane-bound transcription factor peptidase site 1 (MBTPS1), and collagen type VII alpha 1 chain (COL7A1) expression both in vitro and in vivo. This study establishes a strategy for synthesizing HPAEs with ER-targeting ability and identifies potential candidates for skin gene delivery.
UR - https://www.scopus.com/pages/publications/85206539172
U2 - 10.1021/acsmaterialslett.4c01830
DO - 10.1021/acsmaterialslett.4c01830
M3 - 文章
AN - SCOPUS:85206539172
SN - 2639-4979
VL - 6
SP - 5048
EP - 5057
JO - ACS Materials Letters
JF - ACS Materials Letters
IS - 11
ER -