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

다국어 초록 (Multilingual Abstract)

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.
A novel functional nanoparticle (FNP) is designed using the layer‐by‐layer coating method In this framework. The FNPs are able to target Hep G2 cells, escape from the endosome/lysosome to the cytosol, and target to the nucleus. FNPs have promising potential for coincorporating dual or multiple agent delivery with high efficiency.