Kinetically controlled cellular interactions of polymer-polymer and polymer-liposome nanohybrid systems.

Kinetically controlled cellular interactions of polymer-polymer and polymer-liposome nanohybrid systems.
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DOI:
10.1021/bc100484t
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发表时间:
2011-03-16
影响因子:
4.7
通讯作者:
Hong, Seungpyo
Hong, Seungpyo
中科院分区:
化学2区
文献类型:
--
作者:
Sunoqrot, Suhair;Bae, Jin Woo;Jin, Su-Eon;Pearson, Ryan M.;Liu, Ying;Hong, Seungpyo

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虽然生物活性聚合物,如阳离子聚合物已被证明有潜力作为药物载体和非病毒基因传递载体,高毒性和不受控制的,瞬时细胞相互作用的这些载体已经阻碍了在体内的成功实施。因此,对潜在药物/基因递送载体的细胞相互作用的精细控制将是期望的。在本文中,我们设计了纳米混合系统(直径100-150 nm),其将聚阳离子与由可生物降解的聚合物纳米颗粒(NP)或脂质体组成的保护性外层相结合。一种常用的聚阳离子聚乙烯亚胺(PEI)与罗丹明(RITC)共轭后使用。然后将PEI-RITC缀合物包封到:i)由聚丙交酯-共-乙交酯(PLGA)或聚乙二醇-b-聚丙交酯-共-乙交酯(PEG-PLGA)制成的聚合物NP中;或ii)PEG化脂质体中,产生三种纳米杂交系统。通过纳米杂交,细胞摄取和细胞毒性的纳米杂交动力学控制。使用MCF-7细胞的细胞毒性测定显示,在24小时孵育后,基于脂质体的纳米杂化物表现出最小的毒性,其次是基于PEG-PLGA和PLGA的NP。还观察到细胞摄取的不同动力学;基于脂质体的系统是最快的,基于PLGA的系统是最慢的。结果提出了一种潜在的递送平台,其通过尺寸控制对其生物相互作用动力学和被动靶向能力具有增强的控制。
Although bioactive polymers such as cationic polymers have demonstrated potential as drug carriers and nonviral gene delivery vectors, high toxicity and uncontrolled, instantaneous cellular interactions of those vectors have hindered the successful implementation in vivo. Fine control over the cellular interactions of a potential drug/gene delivery vector would be thus desirable. Herein we have designed nanohybrid systems (100–150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymeric nanoparticles (NPs) or liposomes. A commonly used polycation polyethylenimine (PEI) was employed after conjugation with rhodamine (RITC). The PEI-RITC conjugates were then encapsulated into: i) polymeric NPs made of either polylactide-co-glycolide (PLGA) or polyethylene glycol-b-polylactide-co-glycolide (PEG-PLGA); or ii) PEGylated liposomes, resulting in three nanohybrid systems. Through the nano-hybridization, both cellular uptake and cytotoxicity of the nanohybrids were kinetically controlled. The cytotoxicity assay using MCF-7 cells revealed that liposome-based nanohybrids exhibited the least toxicity, followed by PEG-PLGA- and PLGA-based NPs after 24 hr incubation. The different kinetics of cellular uptake was also observed; the liposome-based systems being the fastest and PLGA-based systems being the slowest. The results present a potential delivery platform with enhanced control over its biological interaction kinetics and passive targeting capability through size control.
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