GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment.
GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment.
复制标题
封装恩度的 GX1 缀合聚乳酸纳米颗粒可改善体内抗结直肠癌治疗
DOI：
10.2147/ijn.s82029
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发表时间：
2015
影响因子：
8
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Du Y;Zhang Q;Jing L;Liang X;Chi C;Li Y;Yang X;Dai Z;Tian J
肿瘤血管生成在肿瘤生长和转移中起着关键作用，因此，靶向肿瘤相关血管生成是癌症治疗的重要目标。然而，有效地将药物递送至肿瘤仍然是抗血管生成治疗中的关键问题。GX 1是一种新型的肿瘤血管内皮特异性配体，通过噬菌体展示技术鉴定，在肿瘤的诊断和治疗中具有很大的靶向载体和抗血管生成剂的潜力。Endostar是一种新型的重组人内皮抑素，具有抑制肿瘤血管生成的作用。在这项研究中，我们开发了一种治疗诊断剂，该治疗诊断剂由GX 1缀合的聚乳酸纳米颗粒组成，该纳米颗粒封装了Endostar（GPENs），并用近红外染料IRDye 800 CW标记，以提高体内结直肠肿瘤的靶向和治疗效果。体内荧光分子成像数据显示，GPENs（IRDye 800 CW）比游离IRDye 800 CW更特异性地靶向结直肠肿瘤荷瘤小鼠的肿瘤。此外，通过生物发光成像和免疫组织学评估抗肿瘤功效，揭示与其他处理组相比，GPENs对皮下结直肠异种移植物具有改善的抗肿瘤功效。因此，我们的研究表明，GPENs，一种新的GX 1肽引导形式的纳米级Endostar，可用作治疗诊断剂，以促进更有效的靶向治疗，并能够实时监测体内治疗效果。
Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar (GPENs) and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW) more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo.