Department of Pathology and ⊥Center of Medical Imaging and Image-guided Therapy , Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou 510060 , China.
ACS Appl Mater Interfaces. 2019 Nov 6;11(44):41069-41081. doi: 10.1021/acsami.9b14668. Epub 2019 Oct 24.
Gold nanorods, mesoporous silica, gadolinia, folic acid, and polyethylene glycol (PEG) derivatives have been investigated due to their own advantages in cancer theranostics. However, it remains a great challenge to assemble these components into a stable unity with the diverse and enhanced functionality for more potential applications. Herein, as inspired by the first-principles calculation, a highly stable and safe all-in-one nanoprobe is fabricated via a novel nanoassembly strategy. Multiscale calculations were performed to address the atomistic bonding of a nanoprobe, heat necrosis of a tumor adjacent to the vasculature, and thermal diffusion in a photothermal circumstance, respectively. The nanoprobe gains an 8-fold increase in magnetic resonance imaging (MRI) relaxivity compared to the clinical gadolinium diethylenetriaminepentaacetate, achieving a significant MRI signal in vivo. Conjugated with folate-PEG, the nanoprobe can be effectively absorbed by tumoral cells, obtaining a vivid two-photon cell imaging. A specific multisite scheme for photothermal therapy of a solid tumor is proposed to improve low photothermal efficacy caused by thermal diffusion in a large tumor, leading to the successful cure of the mice with xenograft tumor sized 10-12 mm. In vitro and in vivo toxicity, long-term excretion data, and the recovery of the treated mice demonstrate that the theranostic nanoprobe possesses good biocompatibility and metabolism efficacy.
金纳米棒、介孔硅、钆、叶酸和聚乙二醇（PEG）衍生物因其在癌症治疗学中的自身优势而受到研究。然而，将这些组件组装成具有更多潜在应用的稳定统一体，并具有多样化和增强的功能，仍然是一个巨大的挑战。受第一性原理计算的启发，本文通过一种新的纳米组装策略，制备了一种高度稳定和安全的一体化纳米探针。进行了多尺度计算，分别解决了纳米探针的原子键合、紧邻脉管系统的肿瘤热坏死以及光热环境中的热扩散问题。与临床使用的二乙三胺五乙酸钆相比，该纳米探针的磁共振成像（MRI）弛豫率提高了 8 倍，在体内实现了显著的 MRI 信号。与叶酸-PEG 结合后，纳米探针可以被肿瘤细胞有效吸收，获得生动的双光子细胞成像。提出了一种用于实体瘤光热治疗的特定多部位方案，以提高大肿瘤中热扩散引起的低光热疗效，成功治愈了 10-12 毫米大小的异种移植肿瘤的小鼠。体外和体内毒性、长期排泄数据以及治疗小鼠的恢复情况表明，该治疗诊断纳米探针具有良好的生物相容性和代谢效果。
