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Programmed drug delivery system based on optimized "size decrease and hydrophilicity/hydrophobicity transformation" for enhanced hepatocellular carcinoma therapy of doxorubicin.
Nanomedicine : Nanotechnology, Biology, and Medicine 2018 Februrary 18
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.
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