Shukla Sourabh, DiFranco Nicholas A, Wen Amy M, Commandeur Ulrich, Steinmetz Nicole F
Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA.
Institute for Molecular Biotechnology, RWTH Aachen University, Worringer Weg 1, 52074 Aachen, Germany.
Cell Mol Bioeng. 2015;8(3):433-444. doi: 10.1007/s12195-015-0388-5. Epub 2015 Apr 8.
Nanoparticles are promising platforms for the diagnosis and treatment of cancer. Diverse classes and shapes of materials have been investigated to establish design principles that achieve the effective partitioning of medical cargos between tumors and healthy tissues. Molecular targeting strategies combined with specific nanoparticle shapes confer tissue-specificity on the carriers, allowing the cell-specific delivery of cargos. We recently developed a filamentous platform technology in which the plant virus (PVX) was used as a scaffold. These particles are flexible 515 × 13 nm filaments that encourage passive tumor homing. Here we sought to advance the PVX platform by including a molecular targeting strategy based on cyclic RGD peptides, which specifically bind to integrins upregulated on tumor cells, neovasculature, and metastatic sites. Although the RGD-targeted filaments outperformed the PEGylated stealth filaments , enhanced tumor cell targeting did not translate into improved tumor homing in mouse tumor models. The RGD-PVX and PEG-PVX filaments showed contrasting biodistribution profiles. Both formulations were cleared by the liver and spleen, but only the stealth filaments accumulated in tumors, whereas the RGD-targeted filaments were sequestered in the lungs. These results provide insight into the design principles for virus-based nanoparticles that promote the delivery of medical cargos to the appropriate cell types.
纳米颗粒是用于癌症诊断和治疗的有前景的平台。人们已经研究了多种类型和形状的材料，以确立能够实现药物在肿瘤组织和健康组织之间有效分配的设计原则。分子靶向策略与特定的纳米颗粒形状相结合，赋予载体组织特异性，从而实现药物的细胞特异性递送。我们最近开发了一种丝状平台技术，其中利用植物病毒（PVX）作为支架。这些颗粒是515×13纳米的柔性细丝，可促进被动肿瘤归巢。在这里，我们试图通过纳入基于环状RGD肽的分子靶向策略来推进PVX平台，该肽可特异性结合在肿瘤细胞、新生血管和转移部位上调的整合素。尽管靶向RGD的细丝优于聚乙二醇化隐形细丝，但在小鼠肿瘤模型中，增强的肿瘤细胞靶向并未转化为改善的肿瘤归巢。RGD-PVX细丝和PEG-PVX细丝显示出截然不同的生物分布概况。两种制剂都通过肝脏和脾脏清除，但只有隐形细丝在肿瘤中积累，而靶向RGD的细丝则被隔离在肺部。这些结果为基于病毒的纳米颗粒的设计原则提供了见解，这些原则有助于将药物递送至合适的细胞类型。
