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A Synergistic Polyphosphoester-Based Co-delivery System of an Anticancer Drug Doxorubicin and the Tumor Suppressor Gene P53 for Lung Cancer Therapy

Abstract

Lung cancer is one of the most frequently occurring cancers worldwide and its pathological complexity necessitates combination therapies of various therapeutic elements such as anti-cancer drug and gene to achieve synergistic treatment. In this study, we designed a co-delivery carrier of the anti-cancer drug doxorubicin (DOX) and the tumor suppressor gene p53 for lung cancer treatment. At first, a copolymer precursor (mPEG-b-PBYP) was prepared via ring-opening polymerization of 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane (BYP). Subsequently, on the basis of the precursor, a pH-sensitive prodrug (abbreviated as mPEG-b-PBYP-hyd-DOX) and a polycation gene vector (abbreviated as mPEG-b-PBYP-g-DAE) were separately prepared via CuAAC and thiol-yne “click” chemistry, wherein DAE represents 2-dimethylaminoethanethiol hydrochloride. After that, the prodrug and the gene vector copolymers were mixed in aqueous solution to self-assemble into hybrid micelles, which could condense p53 gene and finally form DOX prodrug/p53 co-loaded nanoparticles. The average particle size and morphologies of the hybrid micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The gel retardation assay showed that the p53 gene could be well immobilized and maintained stably under the electronegative conditions similar to those in the blood circulation. Cytotoxicity assay showed an obvious antitumor effect of hybrid micelles/p53 gene nanoparticles on A549 and H1299 cells in comparison with the case in which the drug or gene therapy is applied alone, respectively. Furthermore, the results from the live cell imaging system revealed that the hybrid micelles/p53 gene nanoparticles could effectively deliver and release DOX and p53 gene into A549 cells. All the results showed that the hybrid micelles containing DOX prodrug and p53 genes could be widely used in the treatment of lung cancer.

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Publication details

The article was received on 19 Mar 2018, accepted on 11 Apr 2018 and first published on 13 Apr 2018


Article type: Paper
DOI: 10.1039/C8TB00746B
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    A Synergistic Polyphosphoester-Based Co-delivery System of an Anticancer Drug Doxorubicin and the Tumor Suppressor Gene P53 for Lung Cancer Therapy

    J. Liu, J. He, M. Zhang, G. Xu and P. Ni, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB00746B

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