Targeted nanoparticles assembled via complexation of boronic-acid-containing targeting moieties to diol-containing polymers.
Targeted nanoparticles assembled via complexation of boronic-acid-containing targeting moieties to diol-containing polymers.
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DOI：
10.1021/bc300640j
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发表时间：
2013-04-17
影响因子：
4.7
通讯作者：
Davis, Mark E.
中科院分区：
文献类型：
--
作者：
Han, Han;Davis, Mark E.
通过掺入靶向能力可以增强经由用于实体癌治疗的纳米级载体递送治疗剂。在这里，我们描述了一种用于组装靶向纳米颗粒的新方法，该方法利用硼酸和二醇之间的可逆共价络合来实现用于递送抗癌药物喜树碱（CPT）的靶向纳米颗粒。CPT与粘酸和PEG（MAP）的生物相容性亲水性共聚物结合。当这种聚合物-药物缀合物被置于水中时，它自组装成约100 μ g/ml的MAP-CPT纳米颗粒。30 nm（直径）和轻微的负zeta电位。抗体赫赛汀通过聚乙二醇（PEG）间隔基与硼酸连接，该含硼酸的靶向部分与含二醇的MAP复合，形成靶向MAP-CPT纳米颗粒。将赫赛汀靶向剂添加到MAP-CPT纳米颗粒中产生具有增加的纳米颗粒尺寸至约100 μ m的靶向MAP-CPT纳米颗粒。40 nm（直径）。通过体外分析发现，CPT从MAP-CPT纳米颗粒中释放的主要机制是水解和脂肪破坏纳米颗粒。与非靶向版本相比，通过每个纳米颗粒掺入单一赫赛汀抗体靶向剂，纳米颗粒的细胞摄取增强了70%。这种单一赫赛汀抗体靶向的MAP-CPT纳米颗粒系统携带约200万个抗体。每纳米颗粒60个CPT分子，并且在小鼠中以10 mg CPT/kg尾静脉注射显示出延长的血浆循环，消除半衰期为21.2 h，AUC值为2766 μg.h/ml。
The delivery of therapeutics via nanoscaled vehicles for solid cancer treatment can be enhanced by the incorporation of a targeting capability. Here, we describe a new method for assembling a targeted nanoparticle that utilizes the reversible covalent complexation between boronic acids and diols to achieve a targeted nanoparticle for the delivery of anti-cancer drug, camptothecin (CPT). CPT is conjugated to a biocompatible, hydrophilic copolymer of mucic acid and PEG (MAP). When this polymer-drug conjugate is placed in water, it self-assembles into MAP-CPT nanoparticles of ca. 30 nm (diameter) and slightly negative zeta potential. The antibody Herceptin is attached to a boronic acid via a polyethylene glycol (PEG) spacer, and this boronic acid-containing targeting moiety is complexed with the diol-containing MAP to form a targeted MAP-CPT nanoparticle. The addition of Herceptin targeting agent to the MAP-CPT nanoparticles yields targeted MAP-CPT nanoparticles with increased nanoparticle size to ca. 40 nm (diameter). The main mechanisms of CPT release from MAP-CPT nanoparticles are found by in vitro analysis to be hydrolysis and nanoparticle disruption by fat. Cellular uptake of nanoparticles is enhanced by 70% compared to non-targeted version by the incorporation of a single Herceptin antibody targeting agent per nanoparticle. This single Herceptin antibody targeted MAP-CPT nanoparticle system carries ca. 60 CPT molecules per nanoparticle and shows prolonged plasma circulation with an elimination half-life of 21.2 h and AUC value of 2766 μg.h/ml at a 10 mg CPT/kg tail vein injection in mice.
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影响因子：
16.6
作者：
Li, Yuanpei;Xiao, Wenwu;Xiao, Kai;Berti, Lorenzo;Luo, Juntao;Tseng, Harry P.;Fung, Gabriel;Lam, Kit S.
通讯作者：
Lam, Kit S.
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
影响因子：
4.7
作者：
Cheng, JJ;Khin, KT;Davis, ME
通讯作者：
Davis, ME
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Phillips, Gail D. Lewis;Li, Guangmin;Sliwkowski, Mark X.
通讯作者：
Sliwkowski, Mark X.