Functionalized PAMAM-based Nanoformulation for Targeted Delivery of 5-Fluorouracil in Hepatocellular Carcinoma.

BACKGROUND: The efficacy of a traditional anticancer drug is challenged by adverse effects of the drug, including its nonspecific bio-distribution, short half-life, and side effects. Dendrimer-based targeted drug delivery system has been considered a promising strategy to increase targeting ability and reduce adverse effects of anti-cancer drugs. OBJECTIVE: This study analyzed the feasibility of whether the anticancer drug 5-fluorouracil (5-FU) could be delivered by functionalized fifth-poly(amidoamine) (PAMAM) with the peptide WP05 and the acetic anhydride to the liver cancer cells, reducing the toxicity of the PAMAM and improving the targeting property of 5-FU during delivery. METHODS: The functionalized PAMAM-based nanoformulation (WP05-G5.0NHAC-FUA) was fabricated through an amide condensation reaction to improve the therapeutic efficacy of 5-Fluorouracil (5-FU) in hepatocellular carcinoma (HCC). The physicochemical structure, particle size, zeta potential, stability, and in vitro release characteristics of WP05-G5.0NHAC-FUA were evaluated. In addition, the targeting, biocompatibility, anti-proliferation, and anti-migration of WP05-G5.0NHAC-FUA were investigated. The anti-tumor effect of WP05-G5.0NHAC-FUA in vivo was evaluated by constructing xenograft tumor models of human hepatoma cells (Bel-7402) implanted in nude mice. RESULTS: The resultant WP05-G5.0NHAC-FUA displayed spherical-like nanoparticles with a size of 174.20 ± 3.59 nm. Zeta potential and the drug loading of WP05-G5.0NHAC-FUA were 5.62 ± 0.41mV and 28.67 ± 1.25%, respectively. Notably, the optimized 5-FU-loaded formulation showed greater cytotoxicity with an IC50 of 30.80 ± 4.04 µg/mL than free 5-FU (114.93 ± 1.43 µg/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free 5-FU in L02 normal liver cells. In vivo animal study further confirmed efficient tumor accumulation and enhanced therapeutic efficiency. CONCLUSION: The developed nanoformulation is a promising platform for the targeting delivery of 5-FU and provides a promising solution for improving the efficacy of hepatocellular carcinoma chemotherapy.

MicroRNA-based potential diagnostic, prognostic and therapeutic applications in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer characterized by high recurrence rates and poor prognosis compared to other breast cancers. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of various post-transcriptional gene and silence a broad set of target genes. Many recent studies have demonstrated that miRNAs play an important role in the initiation, promotion, malignant conversion, progression, and metastasis of TNBC. Therefore, the aim of this review is to focus on recent advancements of microRNAs-based potential applications in diagnosis, treatment and prognosis of triple-negative breast cancer.

Fabrication and characterization of a folic acid-bound 5-fluorouracil loaded quantum dot system for hepatocellular carcinoma targeted therapy.

In the present study, we covalently coupled folic acid (FA) and 5-fluorouracil acetic acid (FUA) on the surface of quantum dots (QDs) to produce a tumor targeting drug delivery system, FA-QDs-FUA. The QDs not only act as hepatocellular carcinoma (HCC)-targeted delivery vehicles, but also play a key role in imaging. The structural and optical properties of as-prepared FA-QDs-FUA were characterized using UV-visible spectra, fluorescence spectra, infrared spectra, particle size and zeta potential. In vitro hemolysis activity, cytotoxicity and targeting specificity of the FA-QDs-FUA system were also evaluated. The in vivo anti-tumor efficacy of FA-QDs-FUA in tumor-bearing mice was investigated. The average particle size and zeta potential of FA-QDs-FUA was 220.28 nm and -13.3 mV, respectively. The drug-loading content of FA-QDs-FUA was 36.85% ± 1.61% (n = 3). The in vitro release profile of 5-FU from FA-QDs-FUA demonstrated a slow and sustained release behaviour as compared to free 5-FU drug. The results of the in vitro cellular experiment demonstrated that FA-QDs-FUA reduced cytotoxicity as compared to free 5-FU and targeted more easily hepatocellular carcinoma cells (SMMC-7721 and HepG2) than normal cells. Mice treated with FA-QDs-FUA showed superior tumor suppression compared to those treated with free 5-FU at 4.72 mg kg-1 of 5-FU. Therefore, the FA-QDs-FUA system can be used as a promising candidate for improving 5-FU efficacy and tumor targeting specificity with limited toxicity.