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aneN3-Based Gemini-Type Amphiphiles with Two-Photon Absorption Properties for Enhanced Nonviral Gene Delivery and Bioimaging
Ma,Le Le1; Tang,Quan1; Liu,Ming Xuan1; Liu,Xu Ying1; Liu,Jin Yu1; Lu,Zhong Lin1; Gao,Yong Guang2; Wang,Ruibing3
2020-09-09
Source PublicationACS Applied Materials and Interfaces
ISSN1944-8244
Volume12Issue:36Pages:40094-40107
AbstractAlthough a plethora of nonviral gene vectors have been developed for potential gene therapy, imageable gemini surfactants with stimuli-responsiveness and high transfection efficiency are still scarce for gene delivery. Herein, three gemini amphiphiles (DEDPP-4/8/12) consisting of an aggregation-induced emission (AIE) central fluorophore: 5,6-diphenylpyrazine-2,3-diester (DEDPP), decorated with triazole-[12]aneN3 as the hydrophilic moiety and alkyl chains of various lengths as the hydrophobic moiety, were designed and synthesized for trackable gene delivery via optical imaging. All three amphiphiles exhibited ultralow critical micelle concentrations (CMCs) (up to 3.40 × 10-6 M), prominent two-photon absorption properties, and solvatochromic fluorescence. Gel electrophoresis assays demonstrated that the migration of plasmid DNA was completely retarded after condensation with these gemini amphiphiles at low concentrations (up to 10 μM). In addition, the ester bond in these amphiphiles may facilitate vector degradation and DNA release, in response to esterase and the acidic environment inside cells. Upon self-assembly with DOPE to form liposomes, DEDPP-8/DOPE achieved the best transfection efficiency in four cell lines, and the transfection efficiency of DEDPP-8/DOPE in HeLa cell lines was 23.5-fold higher than that of Lipo2000, which is unusually high for small organic molecule-based nonviral vectors. Furthermore, excellent transfection efficiency of DEDPP-8/DOPE was obtained in the presence of serum, and the red fluorescence protein (RFP) gene was successfully transfected in zebrafish embryos. Both one- and two-photon fluorescence imaging clearly demonstrated the delivery process of plasmid DNA. This study demonstrated that gemini-type amphiphiles composed of a two-photon fluorophore core conjugated with triazole-[12]aneN3 via an ester bond afforded an unprecedentedly high transfection efficiency with excellent biocompatibility, which may provide new insights for the design and development of multifunctional nonviral gene vectors for imageable gene delivery.
Keywordgemini lipids imageable gene delivery nonviral gene vector two-photon fluorescence [12]aneN3
DOI10.1021/acsami.0c10718
URLView the original
Language英语
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Key Laboratory of Radiopharmaceutics,Ministry of Education,College of Chemistry,Beijing Normal University,Beijing,100875,China
2.Lab for Bone Metabolism,Key Lab for Space Biosciences and Biotechnology,School of Life Sciences,Northwestern Polytechnical University,Xi'an Shaanxi,710072,China
3.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,9990078,Macao
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Ma,Le Le,Tang,Quan,Liu,Ming Xuan,et al. aneN3-Based Gemini-Type Amphiphiles with Two-Photon Absorption Properties for Enhanced Nonviral Gene Delivery and Bioimaging[J]. ACS Applied Materials and Interfaces,2020,12(36):40094-40107.
APA Ma,Le Le.,Tang,Quan.,Liu,Ming Xuan.,Liu,Xu Ying.,Liu,Jin Yu.,...&Wang,Ruibing.(2020).aneN3-Based Gemini-Type Amphiphiles with Two-Photon Absorption Properties for Enhanced Nonviral Gene Delivery and Bioimaging.ACS Applied Materials and Interfaces,12(36),40094-40107.
MLA Ma,Le Le,et al."aneN3-Based Gemini-Type Amphiphiles with Two-Photon Absorption Properties for Enhanced Nonviral Gene Delivery and Bioimaging".ACS Applied Materials and Interfaces 12.36(2020):40094-40107.
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