Reversible glycosidic switch for secure delivery of molecular nanocargos
Reversible glycosidic switch for secure delivery of molecular nanocargos
复制标题
用于分子纳米货物安全输送的可逆糖苷开关
作者：
Pierre;Y. Leu;Yu;K. Wu;Wei;S. Roffler
治疗药物在到达细胞靶点之前可能会从纳米载体中泄漏。在这里，我们描述了化学开关的概念，其响应于环境条件，以在用于有效负载货物的脂溶性状态和用于将货物稳定保留在脂质体内的水溶性状态之间交替。线索响应触发器允许在特定细胞位点释放分子货物。我们证明了一个特定的糖苷开关封装有效的抗癌药物和荧光化合物的效用。药物在脂质体中的稳定保留允许在癌细胞的溶酶体中的糖苷开关的酶促水解后在肿瘤中产生母体药物的高肿瘤/血液比率。糖苷开关脂质体可以治愈荷人乳腺癌肿瘤的小鼠，而没有显着的体重减轻。化学开关是一种在脂质体中装载和保留药物的通用方法，为设计安全有效的脂质体用于治疗和成像提供了新的视角。在这里，作者报告了用糖苷pH敏感开关修饰药物以改善药物的包封和保留，并证明了在体内癌症模型中的应用。
Therapeutic drugs can leak from nanocarriers before reaching their cellular targets. Here we describe the concept of a chemical switch which responds to environmental conditions to alternate between a lipid-soluble state for efficient cargo loading and a water-soluble state for stable retention of cargos inside liposomes. A cue-responsive trigger allows release of the molecular cargo at specific cellular sites. We demonstrate the utility of a specific glycosidic switch for encapsulation of potent anticancer drugs and fluorescent compounds. Stable retention of drugs in liposomes allowed generation of high tumor/blood ratios of parental drug in tumors after enzymatic hydrolysis of the glycosidic switch in the lysosomes of cancer cells. Glycosidic switch liposomes could cure mice bearing human breast cancer tumors without significant weight loss. The chemical switch represents a general method to load and retain cargos inside liposomes, thereby offering new perspectives in engineering safe and effective liposomes for therapy and imaging.Retention of drugs loaded into liposomes is a major challenge to effective targeted drug delivery. Here, the authors report on the modification of drugs with a glycosidic pH sensitive switch to improve encapsulation and retention of drugs and demonstrate application in an in vivo cancer model.
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溶酶体靶向十八烷基罗丹明 B 脂质体可在体外增强戈谢细胞中葡萄糖脑苷脂酶的溶酶体积累。
DOI：
10.2217/nnm.12.138
发表时间：
2013
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Thekkedath,Ritesh;Koshkaryev,Alexander;Torchilin,VladimirP
通讯作者：
Torchilin,VladimirP
影响因子：
11.2
作者：
Y. Matsumura;H. Maeda
通讯作者：
Y. Matsumura;H. Maeda
影响因子：
15
作者：
Barry J;Fritz M;Brender JR;Smith PE;Lee DK;Ramamoorthy A
通讯作者：
Ramamoorthy A
影响因子：
56.9
作者：
Redinbo, MR;Stewart, L;Hol, WGJ
通讯作者：
Hol, WGJ
DOI：
10.1165/ajrcmb.17.3.2837
发表时间：
1997-09-01
影响因子：
6.4
作者：
Chu, YW;Yang, PC;Wu, CW
通讯作者：
Wu, CW