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Polysaccharide-Based Nanoparticles for Two-Step Responsive Release of Antitumor Drug.

ABSTRACT: A novel two-step in situ method for targeted antitumor drug release by supramolecular assembly (Fc-CPT@HACD) was constructed using camptothecin prodrug (Fc-CPT) and β-cyclodextrin (β-CD)-modified hyaluronic acid (HACD). Benefiting from the overexpressed H₂O₂ and glutathione (GSH) in tumor cells, Fc-CPT@HACD can be disassembled by oxidation of ferrocene (Fc) to Fc⁺, leading to an efficient release of the anticancer drug camptothecin (CPT) to induce tumor cell apoptosis without affecting normal cells. The in vivo experiment results also demonstrated that Fc-CPT@HACD possessed higher anticancer efficiency than free CPT, accompanied by negligible side effects.

SUBMITTER: Fu HG

PROVIDER: S-EPMC7294702 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Polysaccharide-Based Nanoparticles for Two-Step Responsive Release of Antitumor Drug.

Fu Hong-Guang HG Chen Yong Y Yu Qilin Q Liu Yu Y

ACS medicinal chemistry letters 20200518 6

A novel two-step in situ method for targeted antitumor drug release by supramolecular assembly (Fc-CPT@HACD) was constructed using camptothecin prodrug (Fc-CPT) and β-cyclodextrin (β-CD)-modified hyaluronic acid (HACD). Benefiting from the overexpressed H2O2 and glutathione (GSH) in tumor cells, Fc-CPT@HACD can be disassembled by oxidation of ferrocene (Fc) to Fc+, leading to an efficient release of the anticancer drug camptothecin (CPT) to induce tumor cell apop ...[more]

PMID: 32551000

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Project description:AimsThe matrix metalloproteinase (MMP) 2/9, also known as collagenases IV and gelatinases A/B, play a key role in cancer invasion and metastasis. However, the clinical trials of the MMP inhibitors (MMPIs) ended up with disappointing results. In this paper, we synthesized a gelatinase-responsive copolymer (mPEG-PCL) by inserting a gelatinase cleavable peptide (PVGLIG) between mPEG and PCL blocks of mPEG-PCL for anticancer drug delivery to make use of MMP2/9 as an intelligent target for drug delivery.Materials and methodsmPEG-pep-PCL copolymer was synthesized via ring-opening copolymerization and double-amidation. To evaluate whether Nanoparticles (NPs) prepared from this copolymer are superior to NPs prepared from mPEG-PCL, NPs prepared from mPEG-PCL copolymer were used as positive control. Docetaxel-loading NPs using mPEG-pep-PCL and mPEG-PCL were prepared by nano-precipitation method, mentioned as Gel-NPs and Con-NPs, respectively. The morphologic changes of the NPs after treatment with gelatinases were observed macroscopically by spectrophotometer and microscopically by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The cellular uptake amount and cytotoxicity of Gel-NPs and Con-NPs, respectively, in cell lines with different levels of gelatinase expression were studied. Moreover, the cytotoxicity study on the primary cancer cells isolated from pericardial fluids from a patient with late-stage lung cancer was conducted.ResultsThe Gel-NPs aggregated in response to gelatinases, which was confirmed macroscopically and microscopically. The cellular uptake amount of Gel-NPs was correlated with the level of gelatinases. The in vitro antitumor effect of Gel-NPs was also correlated with the level of gelatinases and was superior to Taxotere (commercially available docetaxel) as well as the Con-NPs. The cytotoxicity study on the primary lung cancer cells also confirmed the effectiveness of Gel-NPs.ConclusionThe results in this study preliminarily demonstrated the effectiveness of gelatinase-responsive targeting strategy and the prospect of this intelligent nano-drug delivery system though further studies are needed.

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Polysaccharide-Based Nanoparticles for Two-Step Responsive Release of Antitumor Drug.

Publications

Polysaccharide-Based Nanoparticles for Two-Step Responsive Release of Antitumor Drug.

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