前列腺癌靶向的一维碲化物纳米线的制备及光热治疗研究

Photothermal therapy has been proposed as a new approach in the treatment of tumor. In recent years, two-dimensional nanosheets represented by graphene and zero-dimensional nanomaterials represented by various chalcogenide nanocrystals have exhibited excellent photothermal therapy effect. However, there are few studies regarding the photothermal therapy using one-dimensional telluride nanomaterials. In addition, rare studies focused on the photothermal therapy of prostate tumor. A good photothermal performance of one-dimensional telluride nanowires (MTe NWs) is preliminarily revealed by the applicant very recently. As a result, we plan to prepare uniform MTe nanowires through hydrothermal synthesis method at a large scale. The nanowires will be modified by Poly-L-lysine (PLL) to improve the dispersivity and biocompatibility. Then, the prostate tumor specially targeted polypeptide (SP204) will be conjugated onto the surface, resulting in an MTe@PLL-SP204 nanocomposites. The photothermal effect will be investigated and optimized via tuning the composition of nanowires. Additionally, we aim to achieve the special target of tumor by the conjugation of specificity peptide on the surface of nanowires. The fluorescence imaging of nanocomposites after the conjugation of fluorescent dye (Cy5) to confirm the targeting ability. Furthermore, PC3 cells and the prostate tumor bearing nude mouse established using PC3 cells were used to evaluate the in vitro and in vivo photothermal therapy effect of MTe@PLL-SP204 nanocomposites.

光热治疗技术已作为新方案用于肿瘤治疗，近年来以石墨烯为代表的二维纳米片及多种硫族化物纳米晶为代表的零维纳米材料展现出优异的光热治疗效果。但对一维碲化物纳米材料在光热治疗方面的研究还很少，尤其在肿瘤的光热治疗研究中，涉及前列腺癌治疗的报道也很少。申请人近期研究发现一维的碲化物纳米线(MTe)具有非常优异的光热性能。申请人拟采用水热合成法大量制备碲化物纳米线，纳米线表面修饰聚赖氨酸(PLL)以改善材料分散性及生物相容性，具有前列腺癌细胞靶向功能的特异性多肽SP204偶联在其表面，制备MTe@PLL-SP204复合纳米材料。通过对纳米线组分的可控调节优化其光热性能，借助纳米线表面偶联的特异性多肽，实现肿瘤靶向，偶联荧光分子Cy5后的荧光成像验证复合材料的靶向性。使用前列腺癌细胞PC3及PC3构建的裸鼠原位前列腺癌肿瘤模型，评估复合纳米材料在细胞水平和活体水平上对前列腺癌细胞的靶向光热治疗效果。

碲纳米线在可见光-近红外光区域具有600 nm以上的宽峰，这是由禁止跃迁引起的。这表明碲纳米线具有很高的近红外光吸收潜力，我们受此激励，探索碲化物纳米线在肿瘤光热消融上的可行性。我们通过一种简便的方法成功地合成了用聚赖氨酸（PLL）修饰的碲化钯（PdTe）纳米线。这种PLL-PdTe纳米线可实现高效的近红外光成像和光声成像，并具备理想的肿瘤光热治疗效果，可适用于体内外的乳腺癌和前列腺癌的治疗。此外，PLL-PdTe 纳米线没有显示出明显的细胞毒性，并且在体内证实了其长期的生物相容性。因此，PLL-PdTe纳米线可以作为新型的近红外/光声成像治疗剂。PLL-PdTe纳米线的这些结果也鼓励我们继续探索其他碲化物纳米材料的光声诊断和光热治疗应用。我们同时发展了肿瘤的磁热疗来探索纳米复合物以极低的剂量杀死肿瘤细胞的应用。载有疏水性氧化铁纳米粒子和大黄素的铁磁性胶束可快速响应交变磁场，产生的热效应能激活的药物超敏释放，从而实现了磁热疗-化学疗法的联合治疗。除上述研究，我们设计了一些钆基的超小纳米颗粒，这些钆基纳米颗粒具备高弛豫率，能呈现更好的磁共振成像效果。凭借着高于临床商用造影剂Gd-DTPA好几倍的弛豫率，这些纳米级的显影剂实现了显著的磁共振血管造影增强和肿瘤部位的信号明显提升，可应用于临床血池成像和肿瘤诊断。