1. Tumor-Targeting Anti-MicroRNA-155 Delivery Based on Biodegradable Poly(ester amine) and Hyaluronic Acid Shielding for Lung Cancer Therapy.
- Author
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Yang Y, Jia Y, Xiao Y, Hao Y, Zhang L, Chen X, He J, Zhao Y, and Qian Z
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Drug Delivery Systems, Drug Screening Assays, Antitumor, Female, Humans, Hyaluronic Acid administration & dosage, Hyaluronic Acid chemistry, Lung Neoplasms metabolism, Lung Neoplasms pathology, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs genetics, MicroRNAs metabolism, Peptides administration & dosage, Peptides chemistry, Polyamines administration & dosage, Polyamines chemistry, Polyesters administration & dosage, Polyesters chemistry, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Gene Transfer Techniques, Hyaluronic Acid pharmacology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, MicroRNAs antagonists & inhibitors, Peptides pharmacology, Polyamines pharmacology, Polyesters pharmacology
- 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., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
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