Department of Biomedical Engineering , Case Western Reserve University , Cleveland , Ohio 44106 , United States.
Department of NanoEngineering, Moores Cancer Center , University of California-San Diego , La Jolla , California 92093 , United States.
ACS Appl Mater Interfaces. 2018 Nov 21;10(46):39468-39477. doi: 10.1021/acsami.8b12499. Epub 2018 Nov 7.
Nanotechnology holds great promise in cancer drug delivery, and of particular interest are theranostic approaches in which drug delivery and imaging are integrated. In this work, we studied and developed the plant virus tobacco mosaic virus (TMV) as a platform nanotechnology for drug delivery and imaging. Specifically, a serum albumin (SA)-coated TMV formulation was produced. The SA coating fulfils two functions: SA provides a stealth coating for enhanced biocompatibility; it also acts as a targeting ligand enabling efficient tumor accumulation of SA-TMV versus TMV in mouse models of breast and prostate cancer. We demonstrate drug delivery of the chemotherapy doxorubicin (DOX); TMV-delivered DOX outperformed free DOX, resulting in significant delayed tumor growth and increased survival. Furthermore, we demonstrated the ability of SA-coated TMV loaded with chelated Gd(DOTA) for magnetic resonance imaging detection of tumors. In the future, we envision the application of such probes as theranostic, where first imaging is performed to assess whether the nanoparticles are effective at targeting a particular patient tumor. If targeting is confirmed, the therapeutic would be added and treatment can begin. The combination of imaging and therapy would allow to monitor disease progression and therefore inform about the effectiveness of the drug delivery approach.
纳米技术在癌症药物输送中具有巨大的应用潜力,其中特别引人关注的是治疗诊断一体化的方法,即药物输送和成像的一体化。在这项工作中,我们研究和开发了植物病毒烟草花叶病毒(TMV)作为药物输送和成像的平台纳米技术。具体来说,我们制备了一种血清白蛋白(SA)包裹的 TMV 制剂。SA 涂层具有两个功能:SA 提供了一种隐身涂层,以提高生物相容性;它还作为一种靶向配体,使 SA-TMV 比 TMV 更有效地在乳腺癌和前列腺癌的小鼠模型中积累肿瘤。我们展示了化疗药物阿霉素(DOX)的药物输送;TMV 输送的 DOX 优于游离 DOX,导致肿瘤生长明显延迟和存活率提高。此外,我们还证明了负载螯合 Gd(DOTA)的 SA 包裹 TMV 用于磁共振成像检测肿瘤的能力。在未来,我们设想将这些探针应用于治疗诊断一体化,首先进行成像以评估纳米颗粒是否能有效靶向特定患者的肿瘤。如果靶向得到证实,就会添加治疗药物,开始治疗。成像和治疗的结合可以监测疾病的进展,从而了解药物输送方法的有效性。