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

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.

There is still plenty of room for layer-by-layer assembly for constructing nanoarchitectonics-based materials and devices

“…16). 104 Core nanoparticles were first prepared through precipitation of 10-hydroxycamptothecin and aminated poly(lactic-co-glycolic acid). Onto the resulting positive nanoparticles, anionic apoptin plasmids were deposited to form a negatively charged system.…”

Biotin-Targeted Multifunctional Nanoparticles Encapsulating 10-Hydroxycamptothecin and Apoptin Plasmid for Synergistic Hepatocellular Carcinoma Treatment

“…In this study, AP was the main anticancer drug, and HCPT played a synergistic and adjuvant role. In this study, 15% AP was loaded, showing an approximately 3 times higher loading than that of our previous studies due to the conjugation of EPL to PLGA, which increased the zeta potential and expanded the surface adsorption area of PE.…”

“…Most chemotherapy drugs are ineffective due to the loss of P53 function; , however, AP induces apoptosis independent of the P53 pathway. The main apoptotic pathway of AP is the mitochondrial-mediated caspase-3-dependent pathway. ,, Unfortunately, the anticancer effects of AP are limited due to the low expression of apoptotic protease activating factor 1 (apaf-1) . Notably, HCPT can improve the treatment efficiency of AP by promoting the release of cyt C and apaf-1 to accelerate the formation of apoptotic bodies. , …”

Integrin αvβ3-targeted polydopamine-coated gold nanostars for photothermal ablation therapy of hepatocellular carcinoma

“…Surgical resection, systemic chemotherapies, liver transplantation, immunotherapy and molecularly targeted therapy are the common methods for the treatment of HCC [ 2 , 3 ]. However, these methods usually cause side effects and toxicity toward normal tissues, which could not improve the overall survival of HCC patients [ 4 ]. Therefore, it is imperative to discover innovative treatment strategies for effective HCC treatment.…”