A Photoactivatable AIE Polymer for Light-Controlled Gene Delivery: Concurrent Endo/Lysosomal Escape and DNA Unpacking

Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation‐induced emission (AIE) characteristics an...

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Vydáno v:	Angewandte Chemie International Edition Ročník 54; číslo 39; s. 11419 - 11423
Hlavní autoři:	Yuan, Youyong, Zhang, Chong-Jing, Liu, Bin
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Weinheim WILEY-VCH Verlag 21.09.2015 WILEY‐VCH Verlag Wiley Subscription Services, Inc
Vydání:	International ed. in English
Témata:	aggregation-induced emission Aqueous solutions Cytosol Deoxyribonucleic acid DNA DNA - chemistry Electrostatic properties Emission endo/lysosomes Endosomes - metabolism Fluorescence gene delivery Gene transfer Gene Transfer Techniques Genes HeLa Cells Humans Irradiation Light Light irradiation Lysosomes Lysosomes - metabolism Mathematical analysis Nanoparticles Nucleic acids Photochemical Processes Polymers Polymers - chemistry Radiation Reactive oxygen species Reactive Oxygen Species - metabolism Static Electricity Vectors (mathematics) gene delivery aggregation-induced emission endo/lysosomes polymers reactive oxygen species
ISSN:	1433-7851, 1521-3773, 1521-3773
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Shrnutí:	Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation‐induced emission (AIE) characteristics and oligoethylenimine (OEI) conjugated via an aminoacrylate (AA) linker that can be cleaved by reactive oxygen species (ROS). In aqueous media, the polymer could self‐assemble into bright red fluorescent nanoparticles (NPs), which can efficiently bind to DNA through electrostatic interaction for gene delivery. Upon visible light irradiation, the generated ROS can break the endo/lysosomal membrane and the polymer, resulting in light‐controlled endo/lysosomal escape and unpacking of DNA for efficient gene delivery. The smart polymer represents the first successful gene vector to simultaneously address both challenges with a single light excitation process. Special delivery! A photoactive polymeric gene delivery vector can concurrently escape from the endo/lysosome and unpack nucleic acids in cytosol in a single light irradiation process. The polymer, which comprises a fluorogen with aggregation‐enhanced‐emission characteristics and a linker that can be cleaved by reactive oxygen species, forms nanoparticles that bind DNA and are endocytosed by cells.
Bibliografie:	SMART - No. R279-000-378-592 We thank the SMART (R279-000-378-592), the Ministry of Education (R279-000-391-112), Singapore NRF Investigatorship (R279-000-444-281) and the Institute of Materials Research and Engineering of Singapore (IMRE/14-8P1110) for financial support. AIE=aggregation-induced emission. Singapore NRF Investigatorship - No. R279-000-444-281 Institute of Materials Research and Engineering of Singapore - No. IMRE/14-8P1110 ark:/67375/WNG-503C4XX3-X ArticleID:ANIE201503640 Ministry of Education - No. R279-000-391-112 istex:7C11EBDB582E51A0299BEC4015AF04545C31DDEB We thank the SMART (R279‐000‐378‐592), the Ministry of Education (R279‐000‐391‐112), Singapore NRF Investigatorship (R279‐000‐444‐281) and the Institute of Materials Research and Engineering of Singapore (IMRE/14‐8P1110) for financial support. AIE=aggregation‐induced emission. These authors contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1433-7851 1521-3773 1521-3773
DOI:	10.1002/anie.201503640