Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment
Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment
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发表时间：
2007-12
影响因子：
8
通讯作者：
Liping Song;Hui Li;U. Sunar;Juan Chen;I. Corbin;A. Yodh;G. Zheng
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作者：
Liping Song;Hui Li;U. Sunar;Juan Chen;I. Corbin;A. Yodh;G. Zheng
低密度脂蛋白 (LDL) 是天然存在的纳米颗粒，具有生物相容性、可生物降解性和非免疫原性。此外，LDL颗粒的尺寸由其apoB-100成分精确控制（约22 nm），这使其与脂质体和脂质胶束不同。长期以来，LDL 颗粒一直被提议作为纳米载体，用于对 LDL 受体 (LDLR) 阳性癌症进行靶向诊断和治疗。在这里，我们报告了一种新型的基于萘酞菁 (Nc) 的光动力治疗 (PDT) 药物 SiNcBOA 的设计和合成，并描述了其有效重构为 LDL 核心（100:1 有效负载）。 SiNcBOA 具有近红外 (NIR) 吸收波长 (> 800 nm) 和极高的消光系数 (> 10(5) M(-1)cm(-1))，有望治疗深层肿瘤。重构的 LDL 颗粒 (r-Nc-LDL) 保持了天然 LDL 的大小和形状（通过透射电子显微镜测定），并且还保留了癌细胞对 LDLR 介导的摄取（通过共聚焦显微镜观察）。通过无创光学成像技术在体内证实了其相对于正常组织的优先摄取，证明了使用这种纳米颗粒进行近红外成像引导的癌症 PDT 的可行性。
Low density lipoproteins (LDLs) are naturally occurring nanoparticles that are biocompatible, biodegradable and non-immunogenic. Moreover, the size of LDL particle is precisely controlled (approximately 22 nm) by its apoB-100 component, setting them apart from liposomes and lipid micelles. LDL particles have long been proposed as a nanocarrier for targeted delivery of diagnostics and therapeutics to LDL receptor (LDLR)-positive cancers. Here, we report the design and synthesis of a novel naphthalocyanine (Nc)-based photodynamic therapy (PDT) agent, SiNcBOA, and describe its efficient reconstitution into LDL core (100:1 payload). Possessing a near-infrared (NIR) absorption wavelength (> 800 nm) and extremely high extinction coefficient (> 10(5) M(-1)cm(-1)), SiNcBOA holds the promise of treating deeply seated tumors. Reconstituted LDL particles (r-Nc-LDL) maintain the size and shape of native LDL as determined by transmission electron microscopy, and also retain their LDLR-mediated uptake by cancer cells as demonstrated by confocal microscopy. Its preferential uptake by tumor vs normal tissue was confirmed in vivo by noninvasive optical imaging technique, demonstrating the feasibility of using this nanoparticle for NIR imaging-guided PDT of cancer.