Journal
CHEMPHYSCHEM
Volume 19, Issue 16, Pages 2058-2069Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cphc.201701375
Keywords
anti-microRNA-155; cancer therapy; gene therapy; hyaluronic acid shielding; targeted gene delivery
Funding
- National Natural Science Fund for Distinguished Young Scholars [NSFC31525009]
- National Natural Science Fund of China [NSFC31771096]
- Sichuan Innovative Research Team Program for Young Scientists [2016TD0004]
- Distinguished Young Scholars of Sichuan University [2011SCU04B18]
- Guangdong Innovative Research Team Program [2011Y073]
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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 362.7nm and -10.17mV, 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.
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