title: To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous Nanoparticles Based onPotato virus X.
abstract: 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 virusPotato virus X(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 filamentsin vitro, enhanced tumor cell targeting did not translate into improved tumor homingin vivoin 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.
authors: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA.
authors: Sourabh
authors: S
authors: Shukla
authors: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA.
authors: Nicholas A
authors: NA
authors: DiFranco
authors: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA.
authors: Amy M
authors: AM
authors: Wen
authors: Institute for Molecular Biotechnology, RWTH Aachen University, Worringer Weg 1, 52074 Aachen, Germany.
authors: Ulrich
authors: U
authors: Commandeur
authors: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA ; Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA ; Department of Radiology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA ; Department of Materials Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106 USA.
authors: Nicole F
authors: NF
authors: Steinmetz
keywords: Biodistribution; Cancer; Integrins; Nanoparticle shape; Tumor targeting