Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer.
Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer.
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DOI：
10.2147/ijn.s69550
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发表时间：
2014
影响因子：
8
通讯作者：
McGoron AJ
中科院分区：
文献类型：
--
作者：
Fernandez-Fernandez A;Manchanda R;Carvajal DA;Lei T;Srinivasan S;McGoron AJ
基于其光学成像和局部热疗能力，近红外染料可以用作癌症管理的治疗药物。然而，它们的临床可翻译性受到诸如光漂白、循环时间短和非特异性生物分布等问题的限制。菁染料的纳米共轭配方，如IR820，可能能够克服这些限制。我们将IR820与6 kDa聚乙二醇(PEG)-二胺共价偶联，创建了具有体内应用潜力的纳米偶联物（IRPDcov）。共轭过程得到了直径约为150 nm、zeta电位为- 0.4±0.3 mV的近球形、均匀分布的纳米颗粒。与游离染料相比，IRPDcov制剂保留了荧光和引起高温介导的细胞生长抑制的能力，增强了癌细胞的内化和显著增强的细胞毒性热疗效应。此外，与IR820相比，IRPDcov的血浆半衰期、消除半衰期和曲线下面积（AUC）值明显更长（P<0.05），表明小鼠总体暴露于该治疗剂。与游离IR820相比，IRPDcov结合物具有不同的器官定位，其在肾脏的蓄积可能减少，在肺部的蓄积显著降低（P<0.05）。ir820 - peg -二胺纳米偶联物的一些潜在优势可能包括通过增强渗透性和滞留效应来被动靶向肿瘤组织，延长循环时间从而增加联合诊断和治疗的窗口，以及进一步的功能化，靶向和定制机会。聚乙二醇二胺与近红外染料的偶联提供了一种多功能的传递载体，其定位可以用无创技术监测，也可以用于指导热疗癌症治疗。
Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential −0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.