Dataset Information

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

ABSTRACT:

Background

Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells.

Results

In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~?192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations.

Conclusions

Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

SUBMITTER: Wang H

PROVIDER: S-EPMC6513513 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

Wang Haijun H Wu Junzi J Williams Gareth R GR Fan Qing Q Niu Shiwei S Wu Jianrong J Xie Xiaotian X Zhu Li-Min LM

Journal of nanobiotechnology 20190513 1

<h4>Background</h4>Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated ...[more]

PMID: 31084622

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Project description:AIMS: The 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 METHODS: mPEG-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. RESULTS: The 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. CONCLUSION: The 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.

Dataset Information

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

Background

Results

Conclusions

Publications

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

Similar Datasets

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