Use of single-site-functionalized PEG dendrons to prepare gene vectors that penetrate human mucus barriers.
Use of single-site-functionalized PEG dendrons to prepare gene vectors that penetrate human mucus barriers.
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DOI：
10.1002/anie.201208556
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发表时间：
2013-04-02
影响因子：
16.6
通讯作者：
Hanes, Justin
中科院分区：
文献类型：
--
作者：
Kim, Anthony J.;Boylan, Nicholas J.;Suk, Jung Soo;Hwangbo, Minyoung;Yu, Tao;Schuster, Benjamin S.;Cebotaru, Liudimila;Lesniak, Wojciech G.;Oh, Joon Seok;Adstamongkonkul, Pichet;Choi, Ashley Y.;Kannan, Rangaramanujam M.;Hanes, Justin
保护性粘液层是身体在眼睛、呼吸道、胃肠道和宫颈阴道道暴露表面的第一道防线。这些高度粘弹性和粘性的粘液凝胶捕获大多数外来病原体和环境超细颗粒，然后通过粘液清除机制将其清除[1]（根据解剖部位，大约几秒到几小时）。然而，粘液也固定和快速清除治疗性纳米颗粒，包括合成药物载体[2]和临床测试的病毒[3]和非病毒基因载体[4]，因此，代表了在粘膜表面局部药物和基因递送以治疗各种疾病的关键障碍。[1b]为了有效地传递到粘膜表面，基因载体必须足够小以扩散通过粘液网，同时具有粘膜惰性表面以避免粘附到粘液成分。[5]我们之前已经证明，低分子量（MW）聚（乙二醇）（PEG）的致密表面涂层显着改善了聚合物纳米颗粒通过人宫颈阴道粘液（CVM），[5a，6]慢性鼻窦炎粘液，[7]和囊性纤维化（CF）痰的运输，[8]后者通常是最粘稠和弹性的人类粘液分泌物。常规的阳离子基因载体由于其带正电荷，通过与带负电荷的痰组分结合而固定在CF痰中。[9]我们最近发现，唯一临床测试的聚合基因载体，由通过单个半胱氨酸残基CK 30 PEG 10 k与10 kDa PEG缀合的聚-L-赖氨酸组成，被
Protective mucus layers serve as the body s first line of defense at exposed surfaces of the eyes and respiratory, gastrointestinal, and cervicovaginal tracts. These highly viscoelastic and adhesive mucus gels trap most foreign pathogens and environmental ultrafine particles, which are then removed by mucus clearance mechanisms [1](on the order of seconds to a few hours, depending on anatomical site). However, mucus also immobilizes and rapidly clears therapeutic nanoparticles, including synthetic drug carriers [2] and clinically tested viral [3] and nonviral gene vectors,[4] and therefore, represents a critical obstacle to localized drug and gene delivery at mucosal surfaces for the treatment of a variety of diseases.[1b]For efficient delivery to mucosal surfaces, gene vectors must be small enough to diffuse through the mucus mesh, and at the same time possess a muco-inert surface to avoid adhesion to mucus constituents.[5] We have previously demonstrated that a dense surface coating of low-molecularweight (MW) poly (ethylene glycol)(PEG) markedly improved the transport of polymeric nanoparticles through human cervicovaginal mucus (CVM),[5a, 6] chronic rhinosinusitis mucus,[7] and cystic fibrosis (CF) sputum,[8] with the latter being typically the most viscous and elastic human mucus secretion. Conventional cationic gene carriers are immobilized in CF sputum, due to their positive charge, by associating with the negatively charged sputum constituents.[9] We recently showed that the only clinically tested polymeric gene carrier, composed of poly-L-lysine conjugated to 10 kDa PEG through a single cysteine residue, CK30PEG10k, is trapped by
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影响因子：
16.1
作者：
Lai, Samuel K.;Wang, Ying-Ying;Hanes, Justin
通讯作者：
Hanes, Justin
影响因子：
10.8
作者：
DeMattei, CR;Huang, BH;Tomalia, DA
通讯作者：
Tomalia, DA
影响因子：
14
作者：
Suk, Jung Soo;Lai, Samuel K.;Wang, Ying-Ying;Ensign, Laura M.;Zeitlin, Pamela L.;Boyle, Michael P.;Hanes, Justin
通讯作者：
Hanes, Justin
DOI：
10.1073/pnas.95.4.1427
发表时间：
1998-02-17
影响因子：
11.1
作者：
Blessing, T;Remy, JS;Behr, JP
通讯作者：
Behr, JP
影响因子：
4.7
作者：
Petersen, H;Fechner, PM;Kissel, T
通讯作者：
Kissel, T