MMP响应纳米材料,Biomaterials Science

当前位置： X-MOL 学术 › Biomater. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

MMP响应纳米材料
Biomaterials Science ( IF 5.8 ) Pub Date : 2023-08-18 , DOI: 10.1039/d3bm00840a
Jiye Son ₁ , Sadiyah Parveen _{1,

2} , Douglas MacPherson _{1,

3,

4,

5} , Yaron Marciano _{1,

5} , Richard H Huang ₁ , Rein V Ulijn _{1,

3,

6,

7}

Affiliation

基质金属蛋白酶 (MMP) 是降解细胞外基质并调节基本正常细胞行为的酶。自 20 世纪 90 年代以来，抑制这些酶一直是抗癌治疗的策略，但收效甚微。一种新型的 MMP 靶向策略利用了蛋白酶的固有选择性水解活性和随后的催化信号放大，而不是抑制它。使用纳米材料，酶化学反应可以触发抗癌作用的时间和空间激活，放大相关反应，并对癌细胞造成机械损伤或报告。我们分析了近 60 篇文献研究，这些研究结合了化学设计策略，通过四种作用模式实现抗癌效果的空间、时间和机械控制：纳米材料收缩、诱导聚集、细胞毒性纳米纤维的形成以及去聚乙二醇化激活。从文献分析中，我们得出了控制和增强各种化学成分（肽、脂质、聚合物、无机）纳米材料的 MMP 活化的化学设计指南。最后，该综述包括关于如何针对目标 MMP 共同考虑纳米材料的多种特性（例如底物修饰、超分子结构和静电荷）的指南，以实现酶对纳米材料作用的最佳动力学，从而允许获得响应的空间、时间和机械控制的放大和附加水平。尽管本次综述重点关注 MMP 响应性纳米材料在癌症应用中的设计策略，但这些指南预计将推广到以 MMP 为目标治疗或检测癌症和其他疾病的系统，以及其他酶响应性纳米材料。

"点击查看英文标题和摘要"

MMP-responsive nanomaterials

Matrix metalloproteinases (MMP) are enzymes that degrade the extracellular matrix and regulate essential normal cell behaviors. Inhibition of these enzymes has been a strategy for anti-cancer therapy since the 1990s, but with limited success. A new type of MMP-targeting strategy exploits the innate selective hydrolytic activity and consequent catalytic signal amplification of the proteinases, rather than inhibiting it. Using nanomaterials, the enzymatic chemical reaction can trigger the temporal and spatial activation of the anti-cancer effects, amplify the associated response, and cause mechanical damage or report on cancer cells. We analyzed nearly 60 literature studies that incorporate chemical design strategies that lead to spatial, temporal, and mechanical control of the anti-cancer effect through four modes of action: nanomaterial shrinkage, induced aggregation, formation of cytotoxic nanofibers, and activation by de-PEGylation. From the literature analysis, we derived chemical design guidelines to control and enhance MMP activation of nanomaterials of various chemical compositions (peptide, lipid, polymer, inorganic). Finally, the review includes a guide on how multiple characteristics of the nanomaterial, such as substrate modification, supramolecular structure, and electrostatic charge should be collectively considered for the targeted MMP to result in optimal kinetics of enzyme action on the nanomaterial, which allow access to amplification and additional levels of spatial, temporal, and mechanical control of the response. Although this review focuses on the design strategies of MMP-responsive nanomaterials in cancer applications, these guidelines are expected to be generalizable to systems that target MMP for treatment or detection of cancer and other diseases, as well as other enzyme-responsive nanomaterials.

更新日期：2023-08-18

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南