文章信息/Info

Title:

Reducible Polymers for Nucleic Acid Delivery

作者:

何欣榆; 李亞平

(中國(guó)科學(xué)院上海藥物研究所，上海 200031)

Author(s):

HE Xinyu;  LI Yaping

(Shanghai Institute of Materia Medica, The Chinese Academy of Science, Shanghai 200031, China)

關(guān)鍵詞:

還原敏感性材料; 核酸藥物輸送; 二硫鍵

DOI:

10.7502/j.issn.1674-3962.2012.06.06

文獻(xiàn)標(biāo)志碼:

A

摘要:

還原敏感性材料是通過(guò)在高分子材料的主鏈、側(cè)鏈或者交聯(lián)結(jié)構(gòu)中引入二硫鍵合成得到的。由于細(xì)胞內(nèi)外谷胱甘肽等還原性物質(zhì)的濃度相差較大，形成了巨大的還原勢(shì)能梯度，還原敏感性材料作為藥物輸送的載體，能夠在循環(huán)系統(tǒng)和細(xì)胞外液中保持穩(wěn)定，而進(jìn)入細(xì)胞后在高濃度的還原性物質(zhì)作用下迅速降解、釋放藥物，從而顯著提高核酸藥物轉(zhuǎn)染效率，降低高分子材料的毒性，有望作為理想的核酸藥物載體。還原敏感性材料合成方法主要有兩種，一是選擇含有二硫鍵的反應(yīng)物直接參與聚合物的合成或修飾反應(yīng)，二是在聚合物中引入巰基，通過(guò)氧化反應(yīng)，使巰基轉(zhuǎn)變?yōu)槎�硫鍵。本文主要介紹近年來(lái)還原敏感性材料應(yīng)用于核酸藥物輸送的研究進(jìn)展，并根據(jù)引入二硫鍵方法的不同分類(lèi)討論材料的合理設(shè)計(jì)與合成。

Abstract:

Reducible polymers are characterized by introduction of disulfide bonds in their structures. Such polymers remain highly stable in circulation and extracellular environment, but quickly go through degradation and release cargo in the cytosol because of the natural existence of the redox potential gradients between extracellular and intracellular space. This remarkable features render them increased transfection rate and decreased cytotoxicity. Reduction�瞫ensitive polymers show great prospect for construction of ideal nucleic acid delivery system. There are two major approaches used to incorporate reducible bonds in polymers, first synthesizing cationic polymers with reactants which contain disulfide linkages, second introducing thiols into the structures that can convert to disulfide bonds through oxidation. This review discusses recent advances in application of bioreducible polymers for nucleic acid delivery, with particular focus on rational design and synthesis of these polymers.��