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Chemphyschem. 2018 Aug 17;19(16):2058-2069. doi: 10.1002/cphc.201701375. Epub 2018 Feb 28.

Tumor-Targeting Anti-MicroRNA-155 Delivery Based on Biodegradable Poly(ester amine) and Hyaluronic Acid Shielding for Lung Cancer Therapy.

Author information

1
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
2
Research and Development Department, Guangdong Zhongsheng Pharmacy, Dongguan, 523325, P.R. China.
3
National Center for International Research, of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting, Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting, Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi, 530021, P.R. China.
4
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, P.R. China.

Abstract

Anti-microRNA-155 (anti-miR-155), an oligonucleotide with a complimentary sequence to microRNA-155, holds great promise for lung cancer therapy, and thus some cationic materials have been used to deliver anti-miR-155 into lung tumors. Although the gene delivery capacity in vitro was favorable, the application in vivo was limited by rapid removal and significant cytotoxicity, which were mainly caused by the positive charge of the gene complexes. Therefore, it was necessary to develop a novel carrier to decrease the positive charge and increase the gene delivery capacity into the tumor site. In this paper, biodegradable poly(ester amine) (PEA) was used to condense anti-miR-155 into PEA/anti-miR-155 complexes, and natural anionic polysaccharide hyaluronic acid (HA) was modified with a lung tumor cell targeting peptide and then coated on the surface of gene complexes. The formed hyaluronic acid shielding, PEA/anti-miR-155/HA-peptide complexes were monodispersed, and the particle size and zeta potential were 362.7 nm and -10.17 mV, respectively. In addition, the PEA/anti-miR-155/HA-peptide complexes had good biocompatibility and stability in vitro, and the lung tumor growth inhibitions of PEA/anti-miR-155/HA-peptide in vitro and in vivo were also excellent. The PEA/anti-miR-155/HA-peptide complexes play an active role in tumor growth inhibition and could be useful for lung cancer therapy.

KEYWORDS:

anti-microRNA-155; cancer therapy; gene therapy; hyaluronic acid shielding; targeted gene delivery

PMID:
29488305
DOI:
10.1002/cphc.201701375
[Indexed for MEDLINE]

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