含鐵納米藥物催化的腫瘤特異性促氧化可實現抗壞血酸腫瘤化療

含鐵納米藥物催化的腫瘤特異性促氧化可實現抗壞血酸腫瘤化療

作者：

小柯機器人

發布時間：2020/12/17 15:51:45

上海矽酸鹽研究所施劍林研究小組發現，含鐵納米藥物催化的腫瘤特異性促氧化可實現抗壞血酸腫瘤化療。該項研究成果於2020年12月14日在線發表在《美國化學會志》上。

研究人員報導了鐵離子和抗壞血酸負載的中空介孔二氧化矽納米藥物，其通過腫瘤化療催化抗壞血酸的氧化和活性氧的產生。Si–O–Fe–雜化骨架納米藥物不僅能夠實現酸度觸發的降解能力和抗壞血酸釋放能力，而且還提供了豐富的Fe離子源，可催化抗壞血酸的氧化、過氧化氫的形成以及隨後的Fenton反應。

通過兩個單電子反應過程，研究人員詳細探討了Fe3⁺催化的抗壞血酸氧化機理，其中第一個涉及通過抗壞血酸依次捕獲Fe3⁺和O₂形成有利於過氧化氫的金屬-抗壞血酸-氧三元絡合物。體外和體內結果均表明複合納米藥物催化抗壞血酸氧化的抗癌功效顯著增強，從而證明了這種協同治療概念的高度可行性。這種納米藥物設計將有益於抗壞血酸領域的未來發展。

據悉，抗壞血酸是一種歷史悠久的多羥基化合物，已被廣泛認為是一種有效的抗氧化劑。然而，僅在過去的幾十年中，才逐漸發現其在過渡金屬催化劑存在下的促氧化特性，並吸引了化學和生物學研究人員的廣泛關注，這有益於各種實際應用，例如抗癌治療。

附：英文原文

Title: Ascorbate Tumor Chemotherapy by An Iron-Engineered Nanomedicine-Catalyzed Tumor-Specific Pro-Oxidation

Author: Bowen Yang, Jianlin Shi

Issue&Volume: December 14, 2020

Abstract: Ascorbate, a kind of polyhydroxy compound with a long history, has been extensively considered as an efficient antioxidant. However, only in the past several decades its pro-oxidation characteristic in the presence of transition metal catalysts has been gradually uncovered, attracting broad attention from researchers in chemistry and biology for benefiting various practical applications, such as anticancer therapy. In this work, we report catalytic ascorbate oxidation and reactive oxygen species generation for efficient tumor chemotherapy by an iron-engineered and ascorbate-loaded hollow mesoporous silica nanomedicine. The Si–O–Fe– hybrid framework of nanomedicine not only enables acidity-triggered degradability and ascorbate release capability but also provides an abundant Fe ion source for catalyzing ascorbate oxidation, hydrogen peroxide formation, and subsequent Fenton reactions. The detailed chemical mechanism of Fe3+-catalyzed ascorbate oxidation has been explored in detail as two one-electron reaction processes, between which the first one involves the sequential Fe3+ and O2 captures by ascorbate to form a metal–ascorbate–oxygen ternary complex favoring hydrogen peroxide generation. Both in vitro and in vivo results demonstrate the significantly enhanced anticancer efficacy of ascorbate oxidation catalyzed by the composite nanomedicine, demonstrating high feasibility of this synergistic therapeutic concept. It is expected that such a nanomedicine design would be beneficial to future advances in the field of ascorbate.

DOI: 10.1021/jacs.0c09984

Source: https://pubs.acs.org/doi/10.1021/jacs.0c09984