TY - JOUR
T1 - Examining the Cellular Transport Pathway of Fusogenic Quantum Dots Conjugated With Tat Peptide
AU - Dai, Jie
AU - Wang, Jun
AU - Yang, Xuan
AU - Xu, Zixing
AU - Ruan, Gang
N1 - Publisher Copyright:
Copyright © 2022 Dai, Wang, Yang, Xu and Ruan.
PY - 2022/5/27
Y1 - 2022/5/27
N2 - Understanding the underlying transport mechanism of biological delivery is important for developing delivery technologies for pharmaceuticals, imaging agents, and nanomaterials. Recently reported by our group, SDots are a novel class of nanoparticle delivery systems with distinct biointerface features and excellent fusogenic capabilities (i.e., strong ability to interact with the hydrophobic portions of biomembranes). In this study, we investigate the cellular transport mechanism of SDots conjugated with Tat peptide (SDots-Tat) by live-cell spinning-disk confocal microscopy combined with molecular biology methods. Mechanistic studies were conducted on the following stages of cellular transport of SDots-Tat in HeLa cells: cellular entry, endosomal escape, nucleus entry, and intranuclear transport. A key finding is that, after escaping endosomes, SDots-Tat enter the cell nucleus via an importin β-independent pathway, bypassing the usual nucleus entry mechanism used by Tat. This finding implies a new approach to overcome the nucleus membrane barrier for designing biological delivery technologies.
AB - Understanding the underlying transport mechanism of biological delivery is important for developing delivery technologies for pharmaceuticals, imaging agents, and nanomaterials. Recently reported by our group, SDots are a novel class of nanoparticle delivery systems with distinct biointerface features and excellent fusogenic capabilities (i.e., strong ability to interact with the hydrophobic portions of biomembranes). In this study, we investigate the cellular transport mechanism of SDots conjugated with Tat peptide (SDots-Tat) by live-cell spinning-disk confocal microscopy combined with molecular biology methods. Mechanistic studies were conducted on the following stages of cellular transport of SDots-Tat in HeLa cells: cellular entry, endosomal escape, nucleus entry, and intranuclear transport. A key finding is that, after escaping endosomes, SDots-Tat enter the cell nucleus via an importin β-independent pathway, bypassing the usual nucleus entry mechanism used by Tat. This finding implies a new approach to overcome the nucleus membrane barrier for designing biological delivery technologies.
KW - cell-penetrating peptide
KW - delivery
KW - nanoparticle
KW - nucleus entry
KW - quantum dot
KW - targeting
KW - vesicle escape
UR - http://www.scopus.com/inward/record.url?scp=85132289855&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2022.831379
DO - 10.3389/fbioe.2022.831379
M3 - Article
AN - SCOPUS:85132289855
SN - 2296-4185
VL - 10
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 831379
ER -