Well-defined reducible cationic nanogels based on functionalized low-molecular-weight PGMA for effective pDNA and siRNA delivery.
Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. α-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALAT1 siRNA (siR-M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.



Recently, the design of new types of high-performance nanoparticles is of great significance in delivering therapeutics. Nucleic acid-based therapy is a promising treatment option to cure numerous intractable diseases. A facile and straightforward strategy to fabricate safe nucleic acid delivery nanovectors is highly desirable. In this work, based on ethylenediamine-functionalized low-molecular-weight poly(glycidyl methacrylate), a flexible strategy was proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with α-Lipoic acid, one friendly crosslinking reagent, for highly efficient nucleic acid delivery. Such PGED-NGs possess plentiful reducible lipoyl groups, effectively encapsulated pDNA and siRNA and exhibited excellent abilities of nucleic acid delivery. The present work indicated that reducible cationic nanogels involving α-lipoic acid crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Rui-Quan
RQ
Li
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Wei
W
Wu
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Hai-Qing
HQ
Song
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Yanli
Y
Ren
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Ming
M
Yang
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. Electronic address: jianshu_li@scu.edu.cn.
Jianshu
J
Li
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: xufj@mail.buct.edu.cn.
Fu-Jian
FJ
Xu
D002412:Cations; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004247:DNA / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008768:Methylmethacrylates / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008970:Molecular Weight; D000080385:Nanogels; D010957:Plasmids / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism*
D002412:Cations; D008768:Methylmethacrylates; D000080385:Nanogels; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; C000613027:poly(glycerol monomethacrylate); C413692:polyethylene glycol polyethyleneimine nanogel; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA
Gene therapy; Lipoic acid; Nanogel; PGMA; Vector