Anikeeva Nadia, Sykulev Yuri, Delikatny Edward J, Popov Anatoliy V
Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University Philadelphia, Pennsylvania, USA.
Department of Radiology, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania, USA.
Am J Nucl Med Mol Imaging. 2014 Sep 6;4(6):507-24. eCollection 2014.
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.
焦脱镁叶绿酸a（Pyro）是一种近红外（NIR）荧光染料和光敏剂，具有高量子产率，这使得该染料既适合作为成像剂也适合作为治疗剂用于肿瘤治疗。我们基于Pyro与脂质的共轭作用，设计并合成了一系列基于Pyro的近红外探针。我们的探针的性质要求使用亲脂性载体将探针递送至癌细胞膜。为了解决这个问题，我们利用了由聚乙二醇化脂质组成的基于脂质的纳米颗粒（LNP），聚乙二醇化脂质形成纳米颗粒外壳，还有一个脂质核心。为了赋予LNP靶向特性，在组合物中包含次氮基三乙酸（NTA）脂质，其能够实现His标签靶向蛋白的非共价连接并保持其功能活性。我们发现核心分子的性质会影响纳米颗粒的大小、保质期以及在生理温度下的稳定性。两种不同的Pyro-脂质共轭物被加载到LNP的核心或外壳中。随着时间的推移，这些共轭物在靶细胞的细胞膜中积累的能力有所不同。因此，核壳型LNP的模块化组织允许轻松调整其组成，以便微调纳米颗粒的性质以用于体内应用。
