期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 12, 页码 10398-10408出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b01712
关键词
gene delivery; polyethylenimine; ROS-responsive; substance P; Plk1
资金
- National Natural Science Funds of China [21602030, 81172993]
- Shanghai Sailing Program [16YF1400900]
- Scientific Research Foundation of Fudan University for Talent Introduction [JJF301103]
- National Science Fund for Distinguished Young Scholars [81425023]
An ideal gene-carrying vector is supposed to exhibit outstanding gene-condensing capability with positively charged macromolecules to protect the carried gene during in vivo circulation and a rapid dissociation upon microenvironmental stimuli at the aimed sites to release the escorted gene. Currently, it still remains a challenge to develop an ideal gene carrier with efficient transfection ability and low toxicity for clinical applications. Herein, we have innovatively introduced a reactive oxygen species (ROS)-biodegradable boric acid ester linkage in elaborating the design of a gene carrier. In virtue of the featured intracellular characteristics such as the high level of ROS in tumor cells, an ROS-biodegradable electropositive polymer derived from branched polyethylenimine (BPEI) with a low molecular weight (1.2k) through a cross-linking reaction by the boric acid ester bond was developed in this study to achieve condensation and escorting of carried genes. Furthermore, the polymer was modified with substance P (SP) peptide as the targeting ligand through polyethylene glycol. The final fabricated SP-cross-linked BPEI/plasmid DNA nanoparticles exhibit favorable biocompatibility, ROS-deaVability, and fine targeting ability as well as high transfection efficiency compared with parental BPEI1.2k both in vitro and in vivo. SP-cross-linked BPEI/small interfering RNA (pololike kinase 1) polyplex possesses favorable gene-silencing effects in vitro and satisfactory antitumor ability in vivo. Hopefully, this novel cross-linked electropositive polymer may serve well as a safe and efficient gene-delivery vehicle in the clinic.
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