Encapsulation of catalytic functionalities into apoferritin for prodrug delivery.

项目概述：本项目主要设计一种能够通过水解裂解酯、氨基甲酸酯和酰胺键的人工酶。这些实体将用于将前药前体转化为其药理活性衍生物。酶水解在前药活化中起着重要作用。这种方法的新颖之处在于利用人工酶在药理学治疗中实现高度特异性靶向，以提高医学治疗的疗效和毒理学特征。目的是利用载铁蛋白作为生物相容性支架，用于化学催化剂的掺入。铁蛋白是一种储存铁的纳米粒子，在癌症治疗和诊断方面得到了广泛的研究。铁的去除使铁蛋白变成了铁蛋白笼。最终，该项目将提供具有前药活化所需催化活性的工程载铁蛋白。目的：设计一种能催化酯类、氨基甲酸酯类和酰胺类化合物水解的人工酶。方法：蛋白质工程和化学合成。创新点：使用人工酶作为治疗工具。

Project summary: This project is focused on the design of an artificial enzyme able to cleave ester, carbamate and amide bonds by hydrolysis. These entities will be used to convert prodrug precursors into their pharmacologically active derivatives. Enzymatic hydrolysis plays an important role in prodrug activation. The novelty of this approach is the exploitation of artificial enzymes for the achievement of highly specific targeting in pharmacological therapies in order to improve the efficacy and the toxicological profile of medical treatments. The aim is to use the protein apoferritin, as a biocompatible scaffold for the incorporation of chemical catalysts. Ferritin is an iron storage nanoparticle which has been widely studied for cancer therapeutics and diagnostics. Removal of iron turns ferritin into the apoferritin cage. Ultimately, this project will deliver an engineered apoferritin with the catalytic activity required for prodrugs activation. Objective: design of an artificial enzyme able to catalyse the hydrolysis of compounds containing ester, carbamate and amide groups.Approach: protein engineering and chemical synthesis.Novelty: Use of artificial enzyme as therapeutic tool.