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.
Hepatocellular carcinoma (HCC) is
a common cause of death, and
there is a lack of effective treatment methods along with observed
drug resistance. As compared to traditional treatments, drug delivery
systems have been extensively studied and come with unique advantages,
but their clinical applications are limited due to their poor therapeutic
efficacy and severe cytotoxicity. However, multifunctional nanoparticles
(MNPs) provide a strategy for the clinical treatment of tumors. In
this study, MNPs were constructed with a poly(lactic-co-glycolic acid)-ε-polylysine (PLGA-EPL) vehicle for the codelivery
of 10-hydroxycamptothecin (HCPT) and apoptin plasmid (AP) to synergistically
treat HCC. MNPs were surface-modified with biotin (BIO) to improve
their ability to target liver tumor cells. Blank MNPs showed good
biocompatibility in cytotoxicity assays and acute toxicity tests in
BALB/c mice. These MNPs also displayed a good targeting ability as
evidenced by flow cytometry and confocal scanning laser microscopy
analyses. The controlled release ability of these MNPs was confirmed
by drug release and blank nanoparticle degradation assays in vitro.
In vivo antitumor experiments demonstrated the synergistic anticancer
effects of the MNPs, while the synergistic anticancer mechanism was
further explored by Western blotting. Moreover, this study greatly
increased the loading capacity of AP, suggesting the exceptional potential
of MNPs for the treatment of HCC.
The systemic toxicity and low efficacy of traditional chemotherapy for hepatocellular carcinoma (HCC) result in poor clinical outcomes. This study was designed to achieve targeted delivery of apoptin plasmid (AP) to liver tumors and killing of cancer cells using multifunctional nanoparticles (MFNPs) having sustained-release properties. The MFNPs featuring a distinct core-shell structure were prepared using poly(lactic-glycolic acid)-ε-polylysine copolymer and loaded with AP by adsorption. Specific targeting of liver tumor cells was achieved by biotinylation of the nanoparticles (NPs), while an improvement in lysosomal escape and nuclear localization enhanced the tumor cell killing capability of AP. Blank MFNPs exhibited good biocompatibility while AP-loaded NPs were found to exert strong inhibitory effects on both tumor cells in vitro and solid tumors in vivo. Taken together, these findings demonstrate a promising route for the development of tumor-targeted NPs which may lead to improved therapeutic strategies for treating HCC.
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