Reactive Oxygen Species-Biodegradable Gene Carrier for the Targeting Therapy of Breast Cancer.

Abstract

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-cleavability, 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.

• Authors: Chunhui Ruan, Lisha Liu, Qingbing Wang, Xinli Chen, Qinjun Chen, Yifei Lu, Yu Zhang, Xi He, Yujie Zhang, Qin Guo, Tao Sun, Chen Jiang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 10 Issue 12 Pg. 10398-10408 (Mar 28 2018) ISSN: 1944-8252 [Electronic] United States
• PMID: 29498264 (Publication Type: Journal Article)

Chemical References

• Reactive Oxygen Species
• Polyethyleneimine

Topics

• Breast Neoplasms
• Gene Transfer Techniques
• Humans
• Polyethyleneimine
• Reactive Oxygen Species (chemistry)
• Transfection