Harmonizing the Intracellular Kinetics toward Effective Gene Delivery Using Cancer Cell-Targeted and Light-Degradable Polyplexes.
The success of nonviral gene delivery is often restricted by the multiple cellular barriers that posed inconsistent requirements for vector design. High molecular weight (MW) and cationic charge density are required for polycations to enable effective gene encapsulation, which, however, also lead to high toxicity, restricted intracellular cargo release, and poor serum resistance. We herein developed cross-linked polyethylenimine (PEI) with built-in UV-responsive domains (NP-PEI), which can effectively condense DNA while rapidly de-cross-link upon light triggers to promote intracellular DNA release and reduce material toxicity. HA coating of the polyplexes further enhanced their serum stability by shielding the surface positive charges and enabled cancer cell targeting to potentiate the transfection efficiencies. Thus, the polyplexes afforded high transfection efficiencies in serum upon light irradiation, outperforming PEI 25k by 1-2 orders of magnitude. This study therefore provides a useful strategy to overcome the critical barriers against nonviral gene delivery.
Department of General Surgery, Affiliated Shengjing Hospital, China Medical University , Shenyang 110004, China.
Benchun
B
Jiang
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University , Suzhou 215123, China.
Hua
H
He
Department of Nephrology, the First Affiliated Hospital, China Medical University , Shenyang 110001, China.
Li
L
Yao
Department of General Surgery, Affiliated Shengjing Hospital, China Medical University , Shenyang 110004, China.
Tong
T
Zhang
Department of General Surgery, Affiliated Shengjing Hospital, China Medical University , Shenyang 110004, China.
Jianping
J
Huo
Department of General Surgery, Affiliated Shengjing Hospital, China Medical University , Shenyang 110004, China.
Wei
W
Sun
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University , Suzhou 215123, China.
Lichen
0000-0002-4573-0555
L
Yin
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection
D001672:Biocompatible Materials; D004247:DNA; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine