title: Intracellular microenvironment-responsive label-free autofluorescent nanogels for traceable gene delivery.
abstract: Gene therapy presents a unique opportunity for the treatment of genetic diseases, but the lack of multifunctional delivery systems has hindered its clinical applications. Here, a new delivery vector, autofluorescent polyethyleneimine (PEI) nanogels, for highly efficient and traceable gene delivery is developed. Different from commercial high-molecular-weight PEI, the cationic nanogels are noncytotoxic and able to be fragmented due to their unique intracellular microenvironment-responsive structures. The biodegradable nanogels can effectively load plasmid DNA (pDNA), and the self-assembled polyplexes can be cleaved after cellular uptake to improve gene transfection efficiency. Most importantly, the nanogels and the nanogel/pDNA polyplexes are autofluorescent. The fluorescence is stable in blood plasma and responsive to the intracellular microenvironment. The breakup of the nanogels or polyplexes leads to the loss of fluorescence, and thus the gene delivery and carrier biodegradation processes can be monitored. The reported multifunctional system demonstrates excellent biocompatibility, high transfection efficiency, responsive biodegradability, controlled gene release, label-free and simultaneous fluorescence tracking, which will provide a new platform for future scientific investigation and practical implications in gene therapy.
authors: School of Chemical Engineering, The University of Adelaide, Adelaide, SA5005, Australia.
authors: Bingyang
authors: B
authors: Shi
authors: Hu
authors: H
authors: Zhang
authors: Shi Zhang
authors: SZ
authors: Qiao
authors: Jingxiu
authors: J
authors: Bi
authors: Sheng
authors: S
authors: Dai
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment / Q000187:drug effects*; D004247:DNA / Q000008:administration & dosage; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000080385:Nanogels; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry*; D014162:Transfection / Q000379:methods
chemical_list: D005456:Fluorescent Dyes; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA
keywords: gene delivery carriers; intracellular environment; label-free autofluorescence; nanogels; traceable