Cytosolic delivery mediated via electrostatic surface binding of protein, virus, or siRNA cargos to pH-responsive core-shell gel particles.
Cytosolic delivery mediated via electrostatic surface binding of protein, virus, or siRNA cargos to pH-responsive core-shell gel particles.
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DOI：
10.1021/bm801199z
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发表时间：
2009-04-13
影响因子：
6.2
通讯作者：
Irvine, Darrell J.
中科院分区：
文献类型：
--
作者：
Hu, Yuhua;Atukorale, Prabhani U.;Lu, James J.;Moon, James J.;Um, Soong Ho;Cho, Eun Chol;Wang, Yana;Chen, Jianzhu;Irvine, Darrell J.
我们最近描述了一种在细胞内传递大分子的策略，利用pH响应性的核-壳结构凝胶颗粒。这些交联的水凝胶颗粒通过物理隔离无毒亲水壳内破坏内体的‘质子海绵’核心，以低毒的方式扰乱内体。在这里，我们测试了该系统对广泛的大分子货物的胞浆输送的有效性，并展示了通过核壳颗粒将蛋白质、整个病毒颗粒或siRNA寡核苷酸输送到树突状细胞和上皮细胞的胞浆中。我们评估了颗粒递送对疫苗应用的功能影响，发现通过核壳颗粒在树突状细胞胞浆递送蛋白质抗原促进CD8+T细胞以比可溶性蛋白质低100倍的剂量启动。使用这些颗粒传递siRNA后，在上皮细胞中证实了功能基因的下调。基于这些发现，这些材料可能对广泛的生物医学应用感兴趣。
We recently described a strategy for intracellular delivery of macromolecules, utilizing pH-responsive ‘core-shell’ structured gel particles. These crosslinked hydrogel particles disrupt endosomes with low toxicity by virtue of physical sequestration of an endosome-disrupting ‘proton sponge’ core inside a nontoxic hydrophilic shell. Here we tested the efficacy of this system for cytosolic delivery of a broad range of macromolecular cargos, and demonstrate the delivery of proteins, whole viral particles, or siRNA oligonucleotides into the cytosol of dendritic cells and epithelial cells via core-shell particles. We assessed the functional impact of particle delivery for vaccine applications, and found that cytosolic delivery of protein antigens in dendritic cells via the core-shell particles promotes priming of CD8+ T-cells at 100-fold lower doses than soluble protein. Functional gene knockdown following delivery of siRNA using the particles was demonstrated in epithelial cells. Based on these findings, these materials may be of interest for a broad range of biomedical applications.
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影响因子：
64.8
作者：
Houde, M;Bertholet, S;Desjardins, M
通讯作者：
Desjardins, M
影响因子：
3.9
作者：
Amalvy, JI;Unali, GF;Whitby, CP
通讯作者：
Whitby, CP
影响因子：
4.8
作者：
Kumari, Kshama;Gulati, Shelly;Air, Gillian M.
通讯作者：
Air, Gillian M.
DOI：
10.1073/pnas.95.16.9482
发表时间：
1998-08-04
影响因子：
11.1
作者：
Fields, RC;Shimizu, K;Mulé, JJ
通讯作者：
Mulé, JJ
影响因子：
4.1
作者：
Aigner, A
通讯作者：
Aigner, A