期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 14, 期 4, 页码 1111-1122出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.02.006
关键词
Drug delivery system; Size decrease; Hydrophilicity/hydrophobicity transformation; Environment-responsive; Hepatocellular carcinoma therapy
资金
- National Natural Science Foundation for Distinguished Young Scholars [81625023]
- National Natural Science Foundation of China [81473167]
Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear cascading contradictions, especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized size decrease and hydrophilicity/hydrophobicity transformation was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site. Then the degradation of the GNPs triggered by tumor extracellular matrix metalloproteinase-2 (MMP2) led to the release of prodrug Dox-Lac (Mw 898 Da) to facilitate the tumor tissue penetration and cellular uptake. Last, pH-responsive disassociation of Dox-Lac in tumor cells resulted in the free Dox (Mw 543 Da) release to induce toxicity. As expected, GNPs-Dox-Lac achieved superior tumor inhibition rate of 90.8% with low toxicity in vivo, suggesting its potential for enhanced hepatocellular carcinoma (HCC) therapy of doxorubicin in future. (C) 2018 Elsevier Inc. All rights reserved.
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