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Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles to Induce Autophagy-Mediated Liver Cancer Combination Therapy
Wang F.-Z.1; Xing L.1; Tang Z.-H.3; Lu J.-J.3; Cui P.-F.1; Qiao J.-B.1; Jiang L.1; Jiang H.-L.1; Zong L.1
2016-04-04
Source PublicationMolecular Pharmaceutics
ISSN15438392 15438384
Volume13Issue:4Pages:1298-1307
Abstract

Combination therapy has been developed as a promising therapeutic approach for hepatocellular carcinoma therapy. Here we report a low toxicity and high performance nanoparticle system that was self-assembled from a poly(ethylenimine)-glycyrrhetinic acid (PEI-GA) amphiphilic copolymer as a versatile gene/drug dual delivery nanoplatform. PEI-GA was synthesized by chemical conjugation of hydrophobic GA moieties to the hydrophilic PEI backbone via an acylation reaction. The PEI-GA nanocarrier could encapsulate doxorubicin (DOX) efficiently with loading level about 12% and further condense DNA to form PEI-GA/DOX/DNA complexes to codeliver drug and gene. The diameter of the complexes is 102 ± 19 nm with zeta potential of 19.6 ± 0.2 mV. Furthermore, the complexes possess liver cancer targeting ability and could promote liver cancer HepG2 cell internalization. Apoptosis of cells could be induced by chemotherapy of DOX, and PI3K/Akt/mTOR signaling pathway acts a beneficial effect on the modulation of autophagy. Here, it is revealed that utilizing PEI-GA/DOX/shAkt1 complexes results in effective autophagy and apoptosis, which are useful to cause cell death. The induction of superfluous autophagy is reported to induce type-II cell death and also could increase the sensity of chemotherapy to tumor cells. In this case, combining autophagy and apoptosis is meaningful for oncotherapy. In this study, PEI-GA/DOX/shAkt1 has demonstrated favorable tumor target ability, little side effects, and ideal antitumor efficacy.

KeywordAutophagy Combination Therapy Glycyrrhetinic Acid Liver Cancer Targeting Self-assembled
DOI10.1021/acs.molpharmaceut.5b00879
URLView the original
Indexed BySCI
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000373550600011
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Cited Times [WOS]:30   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.China Pharmaceutical University
2.XuZhou Medical University
3.Universidade de Macau
Recommended Citation
GB/T 7714
Wang F.-Z.,Xing L.,Tang Z.-H.,et al. Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles to Induce Autophagy-Mediated Liver Cancer Combination Therapy[J]. Molecular Pharmaceutics,2016,13(4):1298-1307.
APA Wang F.-Z..,Xing L..,Tang Z.-H..,Lu J.-J..,Cui P.-F..,...&Zong L..(2016).Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles to Induce Autophagy-Mediated Liver Cancer Combination Therapy.Molecular Pharmaceutics,13(4),1298-1307.
MLA Wang F.-Z.,et al."Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles to Induce Autophagy-Mediated Liver Cancer Combination Therapy".Molecular Pharmaceutics 13.4(2016):1298-1307.
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