Department of Biomedical Engineering , Case Western Reserve University Schools of Medicine and Engineering , 10900 Euclid Avenue , Cleveland , Ohio 44106 , United States.
Department of Virology , Sri Venkateswara University , Tirupati 517502 , Andhra Pradesh , India.
ACS Appl Mater Interfaces. 2019 May 22;11(20):18213-18223. doi: 10.1021/acsami.9b03956. Epub 2019 May 10.
One of the greatest challenges in nanomedicine is the low efficiency with which nanoparticles are delivered to lesions such as tumors in vivo. Here, we show that Physalis mottle virus (PhMV)-like nanoparticles can be developed as bimodal contrast agents to achieve long circulation, specific targeting capability, and efficient delivery to tumors in vivo. The self-assembling coat protein nanostructure offers various opportunities to modify the internal and external surfaces separately. After loading the internal cavity of the particles with the fluorescent dye Cy5.5 and paramagnetic Gd(III) complexes, we modified the outer surface by PEGylation and conjugation with targeting peptides. Using this combined approach, we were able to monitor a human prostate tumor model for up to 10 days by near-infrared fluorescence and magnetic resonance imaging, with up to 6% of the injection dose remaining. Our results show that PhMV-like nanoparticles provide a promising and innovative platform for the development of next-generation diagnostic and therapeutic agents.
纳米医学面临的最大挑战之一是纳米颗粒向病变(如肿瘤)体内递送的效率低。在这里,我们表明,Physalis mottle virus(PhMV)样纳米颗粒可以作为双模态对比剂开发,以实现长循环、特异性靶向能力和体内高效递送至肿瘤。自组装的外壳蛋白纳米结构提供了各种机会来分别修饰内部和外部表面。在将荧光染料 Cy5.5 和顺磁 Gd(III)配合物装载到颗粒的内部腔后,我们通过 PEG 化和与靶向肽缀合来修饰外表面。使用这种组合方法,我们能够通过近红外荧光和磁共振成像监测人类前列腺肿瘤模型长达 10 天,注射剂量的 6%仍然存在。我们的结果表明,PhMV 样纳米颗粒为开发下一代诊断和治疗剂提供了一个有前途和创新的平台。