To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous Nanoparticles Based on Potato 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 virus Potato 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 filaments in vitro, enhanced tumor cell targeting did not translate into improved tumor homing in vivo 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.

Cancer nanomedicine: progress, challenges and opportunities

“…Furthermore, the use of viral NPs for therapeutic delivery has been facilitated by genetic and chemical engineering techniques 36 . Examples include the use of adeno-associated virus, approved by the European Commission for lipoprotein lipase deficiency 37 , lentivirus currently in various clinical trials for cell-based gene therapy and immunotherapy of various diseases including cancer 38 , and engineered plant viruses (for example, tobacco mosaic virus and potato virus X) for cancer therapy in animal models 39,40 . With their endogenous origin and organ tropism, exosomes have also been proposed for carrying anticancer payloads to target tumours 41 .…”

Dual Functionalized Bacteriophage Qβ as a Photocaged Drug Carrier

“…As the recombinantly expressed and noninfectious structural analogue of a virus, VLPs are still imbued with their native viral resilience against environmental attack, yet as nanometer‐sized macromolecular ensembles, their size, shape, and chemical addressability have allowed them to serve as multivalent scaffolds for the attachment of densely packed MRI contrast agents, fluorescent dyes, and therapeutics . Appropriately functionalized, VLPs show passive tumor accumulation by the enhanced permeability and retention effect yet still have clinically useful and tunable circulation half‐lives—a quality notoriously difficult to imbue into metallic or inorganic nanoparticles.…”

Reconceptualizing Cancer Immunotherapy Based on Plant Production Systems

“…The generation of vaccines and monoclonal antibodies, in a manner that requires little processing or medical infrastructure, strongly supports the exploration of plant-derived biologics as a means to assist developing countries. The recent discovery of plant virus nanoparticles to target and penetrate solid tumors is particularly exciting [ 96 , 97 ]. Nanoparticles based on plant viruses can be readily produced with drugs functionalized to their surfaces, thus enabling them to more easily home in and block tumor progression.…”