These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. Conflict of interest: The authors have declared no conflicts of interest for this article.Īs we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. For further resources related to this article, please visit the WIREs website. In order to better understand the in vivo potential of VLP constructs, we then discuss the interface of protein-cages and the immune system beginning with the nonspecific innate immune system stimulation and continuing into the use of nonpathogenic VLPs as scaffolds for specific antigen presentation and control of the immune response. First we discuss advances in increasing VLP payloads of gadolinium magnetic resonance imaging (MRI) contrast agent as well as controlling the characteristics of individual gadolinium containing molecules to increase efficacy. Here we discuss recent advances by our group toward two parallel and complementary applications of VLPs, derived primarily from plants, bacteriophage, and nonviral sources, in biomedicine: diagnostic imaging and rational vaccine design. An emerging understanding of how viruses interact with the immune system offers a means of precisely designing nanoparticles for biomedical use, both with respect to the structure of the particle as well as their ability to stimulate the immune system. Maintaining or mimicking the symmetry of pathogenic viruses, VLPs offer a ready platform for facilitating recognition, uptake, and processing by the immune system. These results highlight the use of multimeric protein-polymer conjugates for their potential utility in the development of VLP-based MRI contrast agents with the possibility of loading other cargos.Īs ordered nanoscale architectures, viruses and virus-like particles (VLPs) remain unsurpassed by synthetic strategies to produce uniform and symmetric nanoparticles. Using this approach, a significant increase in the labelling density of the VLP, compared to that of previous modifications of VLPs, can be achieved. In particular, the encapsulated polymer can act as a scaffold for the attachment of small functional molecules, such as fluorescein dye or the magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate, through reactions with its pendant primary amine groups. Potentially, this protein-polymer hybrid of P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new high-density delivery vehicle for the encapsulation and delivery of small-molecule cargos. Here we demonstrate a successful site-selective initiation of atom-transfer radical polymerization reactions to form an addressable polymer constrained within the interior cavity of a VLP. Virus-like particles (VLPs) have emerged as important and versatile architectures for chemical manipulation in the development of functional hybrid nanostructures.
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