Core-based lipid nanoparticles as a nanoplatform for delivery of near-infrared fluorescent imaging agents.
Core-based lipid nanoparticles as a nanoplatform for delivery of near-infrared fluorescent imaging agents.
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发表时间：
2014-09
影响因子：
2.5
通讯作者：
N. Anikeeva;Y. Sykulev;E. Delikatny;A. Popov
中科院分区：
文献类型：
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作者：
N. Anikeeva;Y. Sykulev;E. Delikatny;A. Popov
焦脱镁叶绿酸a（Pyro）是具有高量子产率的近红外（NIR）荧光染料和光敏剂，这使得该染料适合作为成像剂和治疗剂用于肿瘤治疗。基于Pyro分子与脂质分子的结合，我们设计并合成了一系列基于Pyro的近红外探针。我们的探针的性质需要使用亲脂性载体将探针递送到癌细胞膜。为了解决这个问题，我们利用了基于脂质的纳米颗粒（LNP），其由形成纳米颗粒壳的PEG化脂质和脂质核心组成。为了赋予LNP靶向性质，在组合物中包括次氮基三乙酸（NTA）脂质，其使得能够非共价连接His标签靶向蛋白质，从而保留其功能活性。我们发现，核心分子的性质影响纳米颗粒的大小，保质期和在生理温度下的稳定性。将两种不同的Pyro-脂质缀合物装载到LNP的核或壳中。缀合物显示了随时间在靶细胞的细胞膜中积累的差异能力。因此，核-壳LNP的模块化组织允许容易地调整其组成，目的是微调用于体内应用的纳米颗粒性质。
Pyropheophorbide a (Pyro) is a near-infrared (NIR) fluorescent dye and photosensitizer with high quantum yield that makes the dye suitable for tumor treatment both as an imaging and therapy agent. We have designed and synthesized a series of a Pyro-based NIR probes, based on the conjugation of Pyro with lipids. The nature of our probes requires the use of a lipophilic carrier to deliver the probes to cancer cell membranes. To address this, we have utilized lipid-based nanoparticles (LNPs) consisting of PEGylated lipids, which form the nanoparticle shell, and a lipid core. To endow the LNPs with targeting properties, nitrilotriacetic acid (NTA) lipids were included in the composition that enables the non-covalent attachment of His-tag targeting proteins preserving their functional activity. We found that the nature of the core molecules influence the nanoparticle size, shelf-life and stability at physiological temperature. Two different Pyro-lipid conjugates were loaded either into the core or shell of the LNPs. The conjugates revealed differential ability to be accumulated in the cell membrane of the target cells with time. Thus, the modular organization of the core-shell LNPs allows facile adjustment of their composition with goal to fine tuning the nanoparticle properties for in vivo application.