In:
Current Pharmaceutical Design, Bentham Science Publishers Ltd., Vol. 28, No. 25 ( 2022-07), p. 2113-2125
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1381-6128
DOI:
10.2174/1381612828666220506111918
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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