ORCID Profile
0000-0002-7014-1891
Current Organisation
KU Leuven
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Publisher: American Scientific Publishers
Date: 04-2016
Abstract: Polyamidoamine dendrimers are potential candidates for drug delivery systems due to their remarkable cell-penetrating power that results from their strong positive surface charge. However, the positively charged surfaces always lead to serious cytotoxicity and the rapid clearance of polyamidoamine in vivo, which limit the application of these dendrimers. To overcome these drawbacks, we developed a carboxymethyl chitosan-modified polyamidoamine dendrimer to achieve progressive drug targeting of tumors via pH-sensitive charge inversion. With the shielding of carboxymethyl chitosan, the complex was negatively charged at physiological conditions (pH 7.4) and prone to enrich at tumor sites due to the enhanced permeation and retention effect however, it regained a positive charge via the removal of the carboxymethyl chitosan coating under tumor-acidic conditions (pH 6.5) and achieved high intracellular uptake in tumor cells through electrostatic adsorptive endocytosis. In this study, these dendrimers exhibited 1.99- and 1.76-times higher cellular uptake efficiencies at pH 7.4 in MCF-7 or A549 cells, respectively, compared with efficiencies at pH 6.5, indicating an effective pH-dependent accumulation the fluorescence intensities of these cells exposed to the dendrimers at pH 6.5 were also 16.45- and 9.27-fold greater, respectively, than those of free doxorubicin. After intravenous administration in mice bearing H22 tumors, doxorubicin-loaded dendrimers exhibited a 1.50-fold greater antitumor activity and presented no obvious systematic toxicity based on histological analysis compared with free drugs. Overall, a simple decoration of carboxymethyl chitosan demonstrated to be a promising way for cationic nanocarriers to achieve pH-sensitive drug release and charge conversion response to tumor microenvironment pH and enhance the antitumor therapy efficiency of anticancer drugs.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.CARBPOL.2017.05.017
Abstract: In this study, we developed bio-stimuli-responsive multi-scale hyaluronic acid (HA) nanoparticles encapsulated with polyamidoamine (PAMAM) dendrimers as the subunits. These HA/PAMAM nanoparticles of large scale (197.10±3.00nm) were stable during systematic circulation then enriched at the tumor sites however, they were prone to be degraded by the high expressed hyaluronidase (HAase) to release inner PAMAM dendrimers and regained a small scale (5.77±0.25nm) with positive charge. After employing tumor spheroids penetration assay on A549 3D tumor spheroids for 8h, the fluorescein isothiocyanate (FITC) labeled multi-scale HA/PAMAM-FITC nanoparticles could penetrate deeply into these tumor spheroids with the degradation of HAase. Moreover, small animal imaging technology in male nude mice bearing H22 tumor showed HA/PAMAM-FITC nanoparticles possess higher prolonged systematic circulation compared with both PAMAM-FITC nanoparticles and free FITC. In addition, after intravenous administration in mice bearing H22 tumors, methotrexate (MTX) loaded multi-scale HA/PAMAM-MTX nanoparticles exhibited a 2.68-fold greater antitumor activity.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CARBPOL.2015.03.019
Abstract: Herein, we developed dualfunctional hyaluronic acid (HA)-grafted polyamidoamine (PAMAM) dendrimers for simultaneous systemic long circulation and active tumor targeting and delivery of topotecan hydrochloride (TPT). The possibility of these modified dendrimers as nanocarriers for promoting tissue distribution and antitumor efficiency, as well as a drug release profile, cytotoxicity and cellular uptake, was investigated. The fine targeting efficiency of HA-PAMAM/TPT was confirmed by the CD44 receptor-mediated high cellular uptake efficiency and low cytotoxicity in HCT-116 cells, and the in vivo higher tumor distribution percentage than in other tissues in mice bearing an S-180 tumor. Pharmacokinetic studies showed that the t1/2 and MRT of TPT were significantly extended after intravenous administration of HA-PAMAM/TPT in normal rats. Moreover, TPT-loaded nanovehicles demonstrated higher antitumor activity compared with free drug and PAMAM/TPT. Overall, HA-PAMAM may be an alternative vector for the effective targeted delivery of and tumor therapy with antitumor drugs.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.NANO.2017.01.008
Abstract: Most nanoparticles (NPs) have difficulty deeply penetrating into tumor tissues. Here, we designed a spatially controlled multistage nanocarrier by encapsulating small polyamidoamine (PAMAM) dendrimers (~5 nm) within large gelatin NPs (~200 nm). This multistage nanocarrier is meant to be stable during systemic circulation and to leak through tumor vasculature walls by the enhanced permeation and retention (EPR) effect. Afterwards, this multistage nanocarrier release PAMAM dendrimers in response to the high matrix metalloproteinase-2 (MMP-2) enzymes in the tumor microenvironment, and further transport into tumor cells. In this study, the demonstrated high intracellular uptake and deep penetration into tumor model verified the effective enzymes-responsively and spatially controlled multistage penetration of these combined nanocarriers. In addition, these multistage nanocarrier were further loaded with anti-tumor drug methotrexate (MTX) and evaluated both in vitro and in vivo to investigate their anti-tumor effect, which demonstrated that this multistage nanocarrier hold great potential in improving anti-tumor efficiency.
Publisher: Wiley
Date: 16-11-2020
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.COLSURFB.2015.06.003
Abstract: Carbon nanotubes (CNTs) are well known for their distinctive drug-loading ability that is mainly due to their large surface area, which permits covalent attachment of various target ligands or drug molecules by π-π stacking, allowing them to act as potential tumor-targeting carriers. Herein, we describe the development of galactosylated chitosan-graftedoxidized CNTs (O-CNTs-LCH) for pH-dependent sustained release and hepatic tumor-targeted delivery of doxorubicin (DOX). The in vitro release behavior in aqueous release media of different pH values (5.5, 6.5 and 7.4) verified the pH-dependent sustained release of DOX from O-CNTs-LCH-DOX. Moreover, these nanocarriers exhibited significant in vitro tumor-targeting properties, with a higher cellular uptake efficiency than that of free DOX in HepG2 cells. In addition, the good biocompatibility and low toxicity of O-CNTs-LCH-DOX was demonstrated by evaluating HepG2 cytotoxicity, vascular irritation and the maximum tolerated dose. Moreover, after intravenous administration in mice bearing the H22 tumor, O-CNTs-LCH-DOX showed higher antitumor activity and stronger fluorescent intensity in tumor tissue compared to free DOX. These results indicated the selective hepatic tumor targeting and the therapeutic effect of those nanocarriers.
No related grants have been discovered for Yuchao Fan.