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使用聚合物生物正交纳米催化剂实现抗癌治疗药物的细胞内激活

Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts.

作者信息

Zhang Xianzhi, Landis Ryan F, Keshri Puspam, Cao-Milán Roberto, Luther David C, Gopalakrishnan Sanjana, Liu Yuanchang, Huang Rui, Li Gengtan, Malassiné Morgane, Uddin Imad, Rondon Brayan, Rotello Vincent M

机构信息

Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.

Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.

出版信息

Adv Healthc Mater. 2021 Mar;10(5):e2001627. doi: 10.1002/adhm.202001627. Epub 2020 Dec 13.

DOI:10.1002/adhm.202001627
PMID:33314745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7933084/
Abstract

Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro-dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal "polyzymes," is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media. The therapeutic potential of these polyzymes is demonstrated by the transformation of a nontoxic prodrug to an anticancer drug (mitoxantrone), leading to the cancer cell death in vitro.

摘要

生物正交催化为成像和治疗应用提供了一种很有前景的策略,可实现前体染料和前体药物的可控原位激活。在这项工作中,展示了使用聚合物支架封装过渡金属催化剂(TMC),从而生成生物正交“多酶”。这些多酶提高了TMC的稳定性,保护催化中心在生物介质中不被失活。通过将无毒前体药物转化为抗癌药物(米托蒽醌),导致体外癌细胞死亡,证明了这些多酶的治疗潜力。

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本文引用的文献

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Design and Engineering of Metal Catalysts for Bio-orthogonal Catalysis in Living Systems.用于生命系统中生物正交催化的金属催化剂的设计与工程
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Bioorthogonal nanozymes: progress towards therapeutic applications.生物正交纳米酶:治疗应用的进展
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Polymer-Based Bioorthogonal Nanocatalysts for the Treatment of Bacterial Biofilms.基于聚合物的生物正交纳米催化剂用于治疗细菌生物膜。
J Am Chem Soc. 2020 Jun 17;142(24):10723-10729. doi: 10.1021/jacs.0c01758. Epub 2020 Jun 8.
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Protection and Isolation of Bioorthogonal Metal Catalysts by Using Monolayer-Coated Nanozymes.利用单层包覆纳米酶保护和隔离生物正交金属催化剂。
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Intracellular Activation of Bioorthogonal Nanozymes through Endosomal Proteolysis of the Protein Corona.通过蛋白冠的内涵体蛋白酶解来实现生物正交纳米酶的细胞内激活
ACS Nano. 2020 Apr 28;14(4):4767-4773. doi: 10.1021/acsnano.0c00629. Epub 2020 Apr 7.
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Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis.负载超薄钯纳米片的癌症衍生外泌体用于靶向生物正交催化
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