Physalis Mottle Virus-like Nanoparticles for Targeted Cancer Imaging

Abstract

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.

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications

“…Fluorescent VLPs are used in optical imaging for specific labeling of cells and tissues in addition to analyzing particular biodistributions, pharmacokinetics and biological interactions [148,184]. The plant virus, CPMV, has been extensively used for optical imaging applications.…”

“…While most VLPs exhibit short circulation times and rapid tissue clearance (~3 days); we discovered that the VLPs from PhMV allow imaging of tumors over extended periods of time (~10 days). In this study, PhMV was modified identically to the aforementioned TMV probe: PhMV was loaded with a NIR dye for optical imaging, Gd-DOTA for MRI, and the Asp-Gly-Glu-Ala targeting peptide; and longitudinal imaging of prostate tumors in vivo was demonstrated [184]. The long residence time within tumors may be utilized to follow disease progression and therapeutic responses.…”

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

“…Whereafter, the cell-penetrating peptide (M-lycotoxin peptide L17E) was attached to siRNA-CCMV to further improve cell uptake and intracellular trafficking. Hu et al 287 designed an integrated NIR fluoresce and MRI bimodal contrast agent based on capsid protein of Physalis mottle virus (PhMV) for targeted PC imaging. PhMV nanoparticles were not only labeled with contrast agents Cy5.5 and Gd 3+ complexes internally, but also conjugated with mPEG and targeting peptides DGEA externally.…”

Macromolecular design and preparation of polymersomes

“…Polymer Chemistry mosaic and hepatitis B have all been studied as vectors for drug delivery and vaccinations. [120][121][122]…”