4.8 Article

Layer-by-Layer Assembly of Functional Nanoparticles for Hepatocellular Carcinoma Therapy

期刊

ADVANCED FUNCTIONAL MATERIALS
卷 29, 期 38, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201904246

关键词

dual targeting; endosomal escape; nucleus targeting; synergistic therapy

资金

  1. National Natural Science Foundation of China [81671683, 81371549]
  2. Science and Technology Foundation of Tianjin [16JCQNJC10200]
  3. Natural Science Foundation of Tianjin [16JC2DJC32200]
  4. Natural Science Foundation of Tianjin City in China [16JCYBJC28600]

向作者/读者索取更多资源

Cancer treatments with conventional approaches often result in limited clinical outcomes due to inefficient therapeutic efficacy and cumulative toxicity against normal tissue. Recently, most research has focused on combined therapeutic studies by functional carriers. In this study, functional nanoparticles (FNPs) are assembled in a layer-by-layer fashion. FNPs are loaded with two drugs (10-hydroxycamptothecin and apoptin plasmid) with dual hepatocellular carcinoma-targeting ligands (lactobionic acid and biotin) on the surface. Cytotoxicity studies and acute toxicity experiments in BAL b/c mice show that blank FNPs demonstrate good biocompatibility. Flow cytometry analysis and cytotoxicity studies demonstrate that the dual-targeting FNPs allow for better specificity and selectivity of the tumor mass. FNPs can escape from endosomal/lysosomal compartments effectively, as is demonstrated using the Cell Navigator lysosome staining kit. When the drugs are released into the cytosol, the nuclear localization signal can enhance the nuclear delivery of 10-hydroxycamptothecin loaded carriers and apoptin plasmids, as is demonstrated by confocal laser scanning microscopy. In vivo experiments show the circulation time and tissue distribution of FNPs, which greatly improve the therapeutic efficacy of BAL b/c nude mice with subcutaneous tumors. Taken together, the results suggest that FNPs are a promising candidate for hepatocellular carcinoma therapy.

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