Chopra Arvind
National Center for Biotechnology Information, NLM, Bethesda, MD 20894
Indocyanine green (ICG) is a water-soluble tricarbocyanine dye with a near-infrared fluorescence (NIRF) absorption maximum between 600 nm and 900 nm and an emission maximum between 750 nm and 950 nm. This is the only dye that has been approved by the United States Food and Drug Administration for noninvasive NIRF imaging to determine the cardiac output, liver function, and blood flow, and to perform ophthalmic angiography in humans (1). Although ICG has wide medical application, it has several drawbacks (due to its physicochemical characteristics) that limit its use in the clinic (2, 3). Briefly, ICG is prone to aggregate and degrade in an aqueous solution and has a short half-life even when stored in the dark ( = 16.8 ± 1.5 h at 22°C) (2). In addition, ICG binds to plasma proteins when administered intravenously and has a blood circulation half-life of only 2–4 min (3). Moreover, the chemical structure of the dye does not allow its conjugation to antibodies or other ligands that can be used to target the probe toward specific cellular components for the detection or diagnosis of various diseases (1). In an effort to improve the stability and circulation half-life of ICG, it was enclosed in nanoparticles (NPs), but the fluorescence signal intensities generated by the various NP formulations were either equivalent to or lower than the signal intensity of the free dye (2). Biodegradable polymer-based NPs (4) and liposomes (5) are considered to be suitable to carry drugs because these nanomaterials are easy to synthesize, are nontoxic, and can be modified on the surface for the targeted delivery of therapeutic agents and imaging probes (5). It has been shown that lipid-polymer hybrid NPs (a biodegradable polymeric core surrounded with a lipid monolayer) exhibit the combined distinctive properties of polymeric NPs and liposomes, and that the hybrid NPs can be used for the targeted delivery of drugs to cells expressing a specific membrane antigen, such as the prostate-specific membrane antigen (6). From this study, it was concluded that such nanocarriers may be used to carry hydrophobic compounds for sustained release and to increase the circulation half-life of a drug; it was also suggested that, after conjugating the hybrid NPs with an appropriate ligand on the surface, the conjugates can be targeted to deliver therapeutic drugs to specific tissues or organs in the body. On the basis of the observations described above, folic acid (FA)–conjugated poly(d,l-lactide-coglycolide) (PLGA)-lipid NPs containing ICG at the core (FA-ICG-PLGA-lipid NPs) were fabricated and evaluated for their targeting characteristics using MCF-7 cells (a human mammary gland adenocarcinoma cell line), which overexpress the folate (FA) receptor (3). The fluorescence imaging properties and biodistribution of the FA-ICG-PLGA-lipid NPs were studied in nude mice bearing MCF-7 cell tumors (3).
吲哚菁绿（ICG）是一种水溶性三碳菁染料，其近红外荧光（NIRF）吸收峰在600纳米至900纳米之间，发射峰在750纳米至950纳米之间。这是唯一一种已获美国食品药品监督管理局批准用于非侵入性NIRF成像以测定心输出量、肝功能和血流量以及在人体中进行眼科血管造影的染料（1）。尽管ICG有广泛的医学应用，但由于其物理化学特性，它存在一些缺点，限制了其在临床上的使用（2,3）。简而言之，ICG在水溶液中容易聚集和降解，即使在黑暗中储存半衰期也很短（22°C时为16.8±1.5小时）（2）。此外，静脉注射时ICG会与血浆蛋白结合，血液循环半衰期仅为2 - 4分钟（3）。而且，该染料的化学结构不允许其与可用于将探针靶向特定细胞成分以检测或诊断各种疾病的抗体或其他配体结合（1）。为了提高ICG的稳定性和血液循环半衰期，将其包裹在纳米颗粒（NPs）中，但各种NP制剂产生的荧光信号强度要么与游离染料的信号强度相当，要么更低（2）。基于生物可降解聚合物的NPs（4）和脂质体（5）被认为适合运载药物，因为这些纳米材料易于合成、无毒，并且可以在表面进行修饰以实现治疗剂和成像探针的靶向递送（5）。已表明脂质 - 聚合物杂化NPs（由脂质单层包围的生物可降解聚合物核心）展现出聚合物NPs和脂质体的独特组合特性，并且这种杂化NPs可用于将药物靶向递送至表达特定膜抗原（如前列腺特异性膜抗原）的细胞（6）。从这项研究得出结论，这种纳米载体可用于运载疏水性化合物以实现持续释放并延长药物的血液循环半衰期；还提出，在将杂化NPs与表面合适的配体偶联后，偶联物可靶向将治疗药物递送至体内特定组织或器官。基于上述观察结果，制备了核心含有ICG的叶酸（FA）偶联聚（d，l - 丙交酯 - 乙交酯）（PLGA） - 脂质NPs（FA - ICG - PLGA - 脂质NPs），并使用过表达叶酸（FA）受体的MCF - 7细胞（人乳腺腺癌细胞系）评估其靶向特性（3）。在携带MCF - 7细胞肿瘤的裸鼠中研究了FA - ICG - PLGA - 脂质NPs的荧光成像特性和生物分布（3）。
