High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles
High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles
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DOI：
10.1117/1.2011429
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发表时间：
2005-07-01
影响因子：
3.5
通讯作者：
Zheng, G
中科院分区：
文献类型：
--
作者：
Li, H;Marotta, DE;Zheng, G
为了提高低密度脂蛋白（LDL）光敏剂（PS）的标记效率以实现高探针-蛋白质负载，设计并合成了在其轴向位置带有两个油酸酯部分的四叔丁基硅酞菁SiPcBOA。使用这种新的策略，获得了具有非常高的有效载荷（SiPcBOA与LDL摩尔比>3000至35001：1）的SiPcBOA重构LDL（r-SiPcBOA-LDL）。使用电子显微镜，我们发现具有如此高的有效载荷的重组LDL（rLDL）基本上保留了天然LDL的平均粒径。由于乙酰化LDL结合内皮细胞和小胶质细胞的清道夫受体而不是LDLR，因此还制备了SiPcBOA重构乙酰化LDL（r-SiPcBOA-AcLDL）作为阴性对照，以验证LDL受体（LDLR）靶向特异性。共聚焦显微镜研究表明，人肝母细胞瘤G（2）（HepG（2））细胞对r-SiPcBOA-LDL的内化是由LDLR途径介导的。使用克隆形成试验将HepG 2细胞对r-SiPcBOA-LDL的体外光动力疗法（PDT）反应与SiPcBOA（游离药物对照）进行比较。拟合这两个图的对数数据的线性回归的斜率彼此显著不同（p =0.0007），表明LDLR靶向PDT的功效大大增强。(C)2005年，由光学仪器工程师学会（Society of Photo-Optical Instrumentation Engineers）主办。
To improve the labeling efficiency of a low-density lipoprotein (LDL)-based photosensitizer (PS) for achieving high probe to protein payload, a tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, SiPcBOA, is designed and synthesized. Using this novel strategy, SiPcBOA reconstituted LDL (r-SiPcBOA-LDL) with a very high payload (SiPcBOA to LDL molar ratio >3000 to 35001 :1) is obtained. Using electron microscopy, we find reconstituted LDL (rLDL) with such a high payload essentially retains the mean particle size of native LDL. Since acetylated LDL binds to scavenger receptors of endothelial and microglial cells instead of LDLR, SiPcBOA reconstituted acetylated LDL (r-SiPcBOA-AcLDL) is also prepared to serve as a negative control to validate the LDL receptor (LDLR) targeting specificity. Confocal microscopy studies demonstrate that the internalization of r-SiPcBOA-LDL by human hepatoblastoma G(2) (HepG(2)) tumor cells is mediated by LDLR pathway. The in vitro photodynamic therapy (PDT) response of HepG2 cells to r-SiPcBOA-LDL is compared to SiPcBOA (free drug control) using a clonogenic assay. The slopes of the linear regression fit to the logarithmic data for these two plots are significantly different from each other (p =0.0007), indicating greatly enhanced efficacy of LDLR-targeted PDT. (C) 2005 Society of Photo-Optical Instrumentation Engineers.