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Synthesis of an Ethyleneimine/tetrahedral DNA Nanostructure Complex and its Potential Application as a Multi‐Functional Delivery Vehicle
Author(s) -
Tian Taoran,
Zhang Tao,
Zhou Tengfei,
Lin Shiyu,
Shi Sirong,
Lin Yunfeng
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.807.1
Subject(s) - biocompatibility , cytotoxicity , materials science , ethyleneimine , drug delivery , gene delivery , lysosome , nanotechnology , cationic polymerization , biophysics , chemistry , cell culture , polymer , transfection , polymer chemistry , composite material , in vitro , organic chemistry , biology , biochemistry , metallurgy , genetics , enzyme
Nowadays, DNA nanostructures are extensively researched for their biocompatibility, editable functionality, and structural stability. Tetrahedral DNA nanostructures (TDNs), widely known for their membrane permeability, are regarded as potential candidates for drug delivery. However, the stability and membrane permeability of TDNs call for further enhancement if in vivo usage is ascribed. To overcome the drawbacks of TDNs, ethylene imine (PEI, 25 kDa, branched)—a classic cationic polymer in the field of gene delivery—was applied. Via a facile one‐pot synthesis method, a PEI/TDNs complex was formed. Subsequently, a DNase protection assay, a cytotoxicity assay, endocytosis‐related experiments, and lysosome staining were performed to examine the potential of PEI/TDNs as a delivery vehicle. The combination of PEI and TDNs not only overcame the drawbacks of each substance but also retained their individual merits. First, via electrostatic forces, PEI/TDNs complexes could be easily synthesized under mild condition. By the modification of PEI, TDNs were condensed and imbibed with stealth surface characteristics, thus enhancing their stability against DNase digestion. Moreover, although PEI is widely criticized for its compromised biocompatibility, in our study, the cytotoxicity was restrained, and cell proliferation was promoted by changing the zeta potential and biomedical effect of TDNs. Lastly, by the aid of PEI, the complex acquires enhanced cell‐entry and lysosome‐escape abilities compared to those of its naked TDNs counterpart. Traditionally, drug delivery vehicles that enable lysosome escape are often limited by their toxicity, ability to carry only limited classes of therapeutic agents, and poor multifunctionality. We believe this novel PEI/TDNs complex with enhanced systemic stability, biocompatibility, cell‐entry ability, and lysosome‐escape ability and unsurpassed editable functionality could be a powerful tool as a multi‐functional delivery vehicle in targeted drug delivery, in vivo imaging, and other related fields. Support or Funding Information This study was supported by the National Natural Science Foundation of China (81671031, 81470721) and Sichuan Province Youth Science and Technology Innovation Team (2014TD0001).Graphical AbstractThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .