Reconstructed viral capsid proteins are attractive nanochemical scaffolds because of their known icosahedral structures, self-assembled and genetically-controlled protein composition, robust stability, monodisperse size and shape, biocompatibility, and polyvalency. They are now commonly used for the display of multiple copies of cell- and tissue-targeting molecules and therapeutic agents on their outer surface or interior space. We describe here the dual functionalization of Q� virus-like particles (VLPs) by encapsulation and surface modification technique, in order to expand the design possibilities of these agents as building blocks for materials science and medicinal applications. Q� VLPs encapsulating multiple copies of fluorescent proteins were generated in high yields using a modular system enhanced by specific engineered RNA-protein interactions. The resulting particles were structurally indistinguishable from recombinant Q� alone. The encapsulated proteins were nearly identical in photochemical properties to monomeric analogues, were more stable toward thermal degradation, and were protected from proteolytic cleavage. Residues on the outer capsid surface were chemically derivatized by acylation and azide-alkyne cycloaddition without affecting the fluorescence properties of the packaged proteins. A high affinity carbohydrate-based ligand of the CD22 receptor was thereby attached, and specific cell labeling by the particles was successfully detected and quantified by flow cytometry and fluorescence microscopy. When simultaneously decorated with metalloporphyrin groups on the exterior surface, the multifunctional particles showed the ability to kill CD22-displaying cells under irradiation by visible light, due to the porphyrin-mediated generation of singlet oxygen. This type of system therefore shows promise for targeted photodynamic therapy, particularly of cells of the immune system.

Cell-targeted photodynamic therapy using virus-like particles

243rd National Meeting (2012)

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