Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, 4072, Australia.
Biomaterials. 2018 Sep;177:40-51. doi: 10.1016/j.biomaterials.2018.05.055. Epub 2018 May 31.
Non-invasive imaging-guided tumor therapy requires new-generation bio-nanomaterials to sensitively respond to the unique tumor microenvironment for precise diagnosis and efficient treatment. Here, we report such a theranostic nanoplatform by engineering defect-rich multifunctional Cu-doped layered double hydroxide (Cu-LDH) nanoparticles, which integrates pH-sensitive T-magnetic resonance imaging (MRI), acid-enhanced photothermal therapy and heat-facilitated chemotherapy. As characterized with EXAFS and XPS, smaller Cu-LDH nanoparticles possess a considerable amount of defects around Cu cations, an advantageous microstructure that enables a high photothermal conversion of 808 nm NIR laser (53.1%). The exposure of CuOH octahedra on the LDH surface makes the photothermal conversion significantly acid-enhanced (53.1% at pH 7.0 vs. 81.9% at pH 5.0). This Cu peculiar microstructure also makes T-MRI very pH-sensitive, a desirable guide for subsequent tumor photothermal therapy. Combined photothermal therapy and chemotherapy lead to nearly complete elimination of tumor tissues in vivo with a low injection dose of agents. Therefore, this novel defect-rich Cu-LDH nanoplatform is one of promising tumor-specific nanotheranostic agents for non-invasive imaging-guided combinational therapy.
非侵入性的影像引导肿瘤治疗需要新一代的生物纳米材料,使其能敏感地响应独特的肿瘤微环境,从而实现精准诊断和高效治疗。在这里,我们通过工程缺陷富多功能铜掺杂层状双氢氧化物(Cu-LDH)纳米粒子,报告了这样一种治疗诊断纳米平台,它集成了 pH 敏感的 T-磁共振成像(MRI)、酸增强光热治疗和热辅助化学治疗。正如 EXAFS 和 XPS 所表征的那样,较小的 Cu-LDH 纳米粒子在 Cu 阳离子周围具有相当数量的缺陷,这种有利的微观结构使 808nm 的近红外激光(53.1%)具有高的光热转换效率。LDH 表面上 CuOH 八面体的暴露使光热转换明显增强(pH 7.0 时为 53.1%,pH 5.0 时为 81.9%)。这种 Cu 特殊的微观结构也使 T-MRI 非常 pH 敏感,是后续肿瘤光热治疗的理想指导。光热治疗和化学治疗的联合作用导致体内肿瘤组织几乎完全消除,而药物的注射剂量很低。因此,这种新型的富含缺陷的 Cu-LDH 纳米平台是一种很有前途的肿瘤特异性纳米治疗诊断剂,可用于非侵入性的影像引导联合治疗。