Affiliation:
1. State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian 116024 China
2. Ningbo Institute of Dalian University of Technology Ningbo 315016 China
3. Research Institute of Dalian University of Technology in Shenzhen Gaoxin South Fourth Road, Nanshan District Shenzhen 518057 China
Abstract
AbstractSmall interfering RNA (siRNA) holds immense promise for suppressing gene expression and treating various life‐threatening diseases, including cancer. However, efficient delivery and lysosomal escape remain critical challenges that hinder the therapeutic effectiveness of siRNA. Herein, cationic photosensitizer (NB‐Br) is grafted onto polo‐like kinase 1 (PLK1) siRNA to form an amphiphilic siRNA‐photosensitizer conjugate (siPLK1‐NB), which can self‐assemble into nanoparticles (siPLK1‐NB NPs) via electrostatic attraction. Notably, siPLK1‐NB NPs exhibit rapid and efficient cell endocytosis, as well as outstanding tumor‐targeting property in multiple tumor‐bearing mice models. When siPLK1‐NB NPs are located inside tumor cell lysosomes, the generated reactive oxygen species (ROS) after photoactivation can disrupt the lysosome membrane structure and facilitate siRNA escape from lysosomes. Under light irradiation, siPLK1‐NB NPs can downregulate PLK1 expression and induce photodynamic killing, effectively inhibiting tumor cell growth both in vitro and in vivo. Consequently, this study provides a novel design strategy for carrier‐free siRNA delivery systems. As far as it is known, this is the first report of a carrier‐free siRNA delivery system based on electrostatic attraction.
Funder
National Natural Science Foundation of China
Basic Research Fund for Free Exploration
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
20 articles.
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