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首页> 外文期刊>Advanced Functional Materials >A Multi-Gradient Targeting Drug Delivery System Based on RGD-L-TRAIL-Labeled Magnetic Microbubbles for Cancer Theranostics
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A Multi-Gradient Targeting Drug Delivery System Based on RGD-L-TRAIL-Labeled Magnetic Microbubbles for Cancer Theranostics

机译：基于RGD-L-TRAIL标签的磁性微泡的多梯度靶向药物递送系统用于肿瘤治疗

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摘要

The accurately and efficiently targeted delivery of therapeutic/diagnostic agents into tumor areas in a controllable fashion remains a big challenge. Here, a novel cancer targeting magnetic microbubble is elaborately fabricated. First, the gamma-Fe2O3 magnetic iron oxide nanoparticles are optimized to chemically conjugate on the surface of polymer microbubbles. Then, arginine-glycine-aspartic acid-l-tumor necrosis factor-related apoptosis-inducing ligand (RGD-l-TRAIL), antitumor targeting fusion protein, is precisely conjugated with magnetic nanoparticles of microbubbles to construct RGD molecularly targeted magnetic microbubble, which is defined as RGD-L-TRAIL@MMBs. Such RGD-L-TRAIL@MMBs is endowed with the multigradient cascade targeting ability following by magnetic targeting, RGD, as well as enhanced permeability and retention effect regulated targeting to result in high cancerous tissue targeting efficiency. Due to the highly specific accumulation of RGD-L-TRAIL@MMBs in the tumor, the accurate diagnostic information of tumor can be obtained by dual ultrasound and magnetic resonance imaging. After imaging, the TRAIL molecules as anticancer agent also get right into the cancer cells by nanoparticle- and RGD-mediated endocytosis to effectively induce the tumor cell apoptosis. Therefore, RGD-l-TRAIL conjugated magnetic microbubbles could be developed as a molecularly targeted multimodality imaging delivery system with the addition of chemotherapeutic cargoes to improve cancer diagnosis and therapy.
机译：以可控的方式将治疗/诊断剂准确有效地靶向治疗仍是一大挑战。在这里，精心制作了一种新型的靶向磁性微泡的癌症。首先，对γ-Fe2O3磁性氧化铁纳米粒子进行优化，以使其化学共轭在聚合物微气泡的表面上。然后，将精氨酸-甘氨酸-天冬氨酸-1-肿瘤坏死因子相关的凋亡诱导配体（RGD-1-TRAIL），抗肿瘤靶向融合蛋白与微泡的磁性纳米颗粒精确偶联，以构建RGD分子靶向的磁微泡。被定义为RGD-L-TRAIL @ MMBs。这种RGD-L-TRAIL @ MMBs具有多梯度级联靶向能力，随后是磁性靶向，RGD，以及增强的渗透性和保留效应调控的靶向，从而导致高癌组织靶向效率。由于RGD-L-TRAIL @ MMBs在肿瘤中的高度特异性积累，可以通过双超声和磁共振成像获得准确的肿瘤诊断信息。成像后，作为抗癌剂的TRAIL分子也通过纳米颗粒和RGD介导的内吞作用而进入癌细胞，从而有效诱导肿瘤细胞凋亡。因此，RGD-1-TRAIL共轭的磁性微泡可以开发成分子靶向多模态成像递送系统，并添加化疗药物以改善癌症的诊断和治疗。

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  • 来源
    《Advanced Functional Materials》 |2016年第45期|8313-8324|共12页
  • 作者

    Duan Lei; Yang Fang; He Wen; Song Lina; Qiu Fan; Xu Ning; Xu Lu; Zhang Yu; Hua Zichun; Gu Ning;

  • 作者单位

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China|Nanjing Med Univ, Sch Basic Med Sci, Nanjing 210029, Jiangsu, Peoples R China;

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China;

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China;

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China;

    Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210023, Jiangsu, Peoples R China;

    Nanjing Med Univ, Sch Basic Med Sci, Nanjing 210029, Jiangsu, Peoples R China;

    Nanjing Med Univ, Sch Basic Med Sci, Nanjing 210029, Jiangsu, Peoples R China;

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China;

    Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210023, Jiangsu, Peoples R China;

    Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing 210096, Jiangsu, Peoples R China;

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