Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles
Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles
复制标题
iRGD修饰吲哚菁绿纳米粒子分子成像引导光热/光动力治疗肿瘤
DOI：
10.1016/j.jconrel.2015.12.050
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发表时间：
2016-02-28
影响因子：
10.8
通讯作者：
Zheng, Hairong
中科院分区：
文献类型：
--
作者：
Yan, Fei;Wu, Hao;Zheng, Hairong
多功能近红外（NIR）纳米粒子在肿瘤治疗诊断应用中显示出巨大的潜力。为了在肿瘤发生的早期阶段实现灵敏的检测和有效的光疗，非常期望改善NIR治疗诊断剂对生物标志物的靶向并增强其在肿瘤中的积累。本文报道了一种新型靶向多功能治疗诊断纳米粒--内化RGD（iRGD）修饰的吲哚菁绿色（ICG）脂质体（iRGD-ICG-LPs），用于分子成像引导的光热疗法（PTT）和光动力疗法（PDT）治疗乳腺肿瘤。首先利用对α v β 3整合素具有高亲和力和有效的肿瘤内化特性的iRGD肽合成iRGD-PEG（2000）-DSPE脂肽，并进一步利用其制备靶向ICG脂质体。结果表明，iRGD-ICG-LPs具有良好的稳定性，可用于乳腺肿瘤的近红外荧光分子成像检测。我们进一步将这种纳米颗粒用于肿瘤治疗诊断应用，通过PTT/PDT效应证明了显著更高的肿瘤积累和肿瘤抑制功效。组织学分析进一步揭示了更多的凋亡细胞，证实了iRGD-ICG-LP相对于非靶向ICG-LP的有利的抗肿瘤作用。值得注意的是，iRGD介导的靶向治疗提供了几乎等同的抗肿瘤疗效，而药物剂量比单克隆抗体低12.5倍，并且在我们的研究中没有观察到肿瘤复发和明显的治疗诱导毒性。我们的研究提供了一个很有前途的策略，实现敏感的检测和有效的治疗肿瘤的分子成像结合PTT/PDT治疗。(C)2015年由Elsevier B. V.出版
Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to alpha v beta 3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG(2000)-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealedmuchmore apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy. (C) 2015 Published by Elsevier B.V.