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在水中合成荧光、小尺寸、稳定且无毒的表位印迹聚合物纳米颗粒。

Synthesis of Fluorescent, Small, Stable and Non-Toxic Epitope-Imprinted Polymer Nanoparticles in Water.

作者信息

Benghouzi Perla, Louadj Lila, Pagani Aurélia, Garnier Maylis, Fresnais Jérôme, Gonzato Carlo, Sabbah Michèle, Griffete Nébéwia

机构信息

Physico-Chimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Sorbonne Université, CNRS, 4 Place Jussieu, 75005 Paris, France.

Saint-Antoine Research Center (CRSA) INSERM, CNRS, Sorbonne Université, 75012 Paris, France.

出版信息

Polymers (Basel). 2023 Feb 23;15(5):1112. doi: 10.3390/polym15051112.

DOI:10.3390/polym15051112
PMID:36904354
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10007256/
Abstract

Molecularly imprinted polymers (MIPs) are really interesting for nanomedicine. To be suitable for such application, they need to be small, stable in aqueous media and sometimes fluorescent for bioimaging. We report herein, the facile synthesis of fluorescent, small (below 200 nm), water-soluble and water-stable MIP capable of specific and selective recognition of their target epitope (small part of a protein). To synthesize these materials, we used dithiocarbamate-based photoiniferter polymerization in water. The use of a rhodamine-based monomer makes the resulting polymers fluorescent. Isothermal titration calorimetry (ITC) is used to determine the affinity as well as the selectivity of the MIP for its imprinted epitope, according to the significant differences observed when comparing the binding enthalpy of the original epitope with that of other peptides. The toxicity of the nanoparticles is also tested in two breast cancer cell lines to show the possible use of these particle for future in vivo applications. The materials demonstrated a high specificity and selectivity for the imprinted epitope, with a K value comparable with the affinity values of antibodies. The synthesized MIP are not toxic, which makes them suitable for nanomedicine.

摘要

分子印迹聚合物(MIPs)在纳米医学领域极具吸引力。为适用于此类应用,它们需体积小、在水性介质中稳定,有时还需具备用于生物成像的荧光特性。我们在此报告了一种简便的合成方法,可制备出荧光、小尺寸(低于200 nm)、水溶性且水稳定的MIP,其能够特异性且选择性地识别其目标表位(蛋白质的一小部分)。为合成这些材料,我们在水中使用基于二硫代氨基甲酸盐的光引发转移终止剂聚合反应。使用基于罗丹明的单体使得所得聚合物具有荧光性。等温滴定量热法(ITC)用于根据比较原始表位与其他肽的结合焓时观察到的显著差异,来确定MIP对其印迹表位的亲和力以及选择性。还在两种乳腺癌细胞系中测试了纳米颗粒的毒性,以展示这些颗粒在未来体内应用中的潜在用途。这些材料对印迹表位表现出高特异性和选择性,其K值与抗体的亲和力值相当。合成的MIP无毒,这使其适用于纳米医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/695692579cc5/polymers-15-01112-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/49f7782d356a/polymers-15-01112-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/30c9310dae8b/polymers-15-01112-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/308b8bcd69c7/polymers-15-01112-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/2470a77e33dd/polymers-15-01112-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/f96603b4f598/polymers-15-01112-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/900a6063cfaa/polymers-15-01112-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/d09f17d1d8e3/polymers-15-01112-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/695692579cc5/polymers-15-01112-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/49f7782d356a/polymers-15-01112-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/30c9310dae8b/polymers-15-01112-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/308b8bcd69c7/polymers-15-01112-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/2470a77e33dd/polymers-15-01112-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/f96603b4f598/polymers-15-01112-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/900a6063cfaa/polymers-15-01112-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/d09f17d1d8e3/polymers-15-01112-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/10007256/695692579cc5/polymers-15-01112-g005.jpg

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本文引用的文献

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Hybrid Molecularly Imprinted Polymers: The Future of Nanomedicine?混合分子印迹聚合物:纳米医学的未来?
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Molecularly Imprinted Nanoparticles (NanoMIPs) Selective for Proteins: Optimization of a Protocol for Solid-Phase Synthesis Using Automatic Chemical Reactor.对蛋白质具有选择性的分子印迹纳米颗粒(纳米MIPs):使用自动化学反应器优化固相合成方案
Polymers (Basel). 2021 Jan 20;13(3):314. doi: 10.3390/polym13030314.
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Molecularly Imprinted Polymer Nanoparticles: An Emerging Versatile Platform for Cancer Therapy.
分子印迹聚合物纳米粒子:癌症治疗的新兴多功能平台。
Angew Chem Int Ed Engl. 2021 Feb 19;60(8):3858-3869. doi: 10.1002/anie.202005309. Epub 2020 Nov 23.
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Molecularly Imprinted Polymers: Antibody Mimics for Bioimaging and Therapy.分子印迹聚合物:用于生物成像和治疗的抗体模拟物
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