CAREER: Viral Capsids as Smart Nanocontainers

University Of Texas At Dallas, Richardson TX

Investigators

Abstract

Non-technical: This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Dallas is to study protein-based nanoparticles using non-infectious and non-toxic virus capsids as scaffolding materials for possible drug delivery applications. Nanoparticle-based drug delivery systems have traditionally focused on using nanoparticles derived from metals, silica, polymers, etc. However, some of these materials have encountered roadblocks in their applications. For instance, nanoparticles based on inorganic and polymeric materials typically take a long time in clearing by the body, and possible accumulation in different organs. One possible solution is to make nanoparticles from proteins using non-infectious and non-toxic virus particles as a scaffolding. Conceptually, viruses are ideal for drug delivery system as they have been evolutionarily endowed with all the resources and properties needed to deliver a cargo to specific cells. However, one of the issues holding back in the use of protein-based nanoparticles for drug delivery is the lack of synthetic chemistries under conditions that don't cause unfolding or a denaturation of the proteins of the virus particles during their preparation. One of the thrusts of this proposal is in developing several new reaction methods and building a tool kit for future applications. These new reactions would enable to look at new approaches for drug release from protein-based nanoparticles, including the use of external trigger sources like pulsed laser light. To accomplish this, this project will functionalize the protein nanoparticles with 'photo-thermal antennae' that when struck by the appropriate wavelength of light, will result in the rupture of the capsids and release of their contents (cargo, drugs, etc.) into the cell. An important benefit of this research is that this study is multidisciplinary in nature, and readily lends itself to creating a collaborative environment for student teaching and training. These efforts will be harnessed by giving these students opportunities in creating a web-based comics program, which are expected not only to educate, but also entertain school-aged K-12 children and their parents by telling stories on how nanomaterials interact with the body, and how they could help bring about future drug delivery systems for many biomedical applications. Technical: The main objective of this CAREER award is to synthesize thermally responsive protein-based nanoscopic molecular drug delivery system prepared from virus derived nanoparticles that are non-infectious and non-toxic. Many of the current approaches for releasing contents of nanoparticles - either macromolecular or small molecule - depend on exploiting the cellular environment. The significant part of this award is to expand the variety and scope of reactions available for the functionalization of protein-based nanoparticles from virus-like particles QB (VLPs QB). Additionally, this award will study novel approaches in seeking the development of a method to permit cargo release using external sources of radiation - in particular optical radiation. To these ends, this project will focus on two objectives: 1) using a virus-like particles derived from QB as a model, this award will develop bioconjugation chemistries focusing on the disulfide groups found in viral capsid surfaces without significantly undermining the thermal stability of viral particle; and 2) introducing photothermally active receptors (antennae) on the surface of the proteinaceous surface of QB virus particles, and these modified viral particles when exposed to pulsed laser irradiation will cause rapid heating and cooling of the nano carriers resulting in the ruptue of the particles, and this in turn will result in the release of cargo/drug stored inside the VLP. This project, in addition, will demonstrate concurrent bilayer membrane disruption with cargo release as an alternate approach to escape from endosome capture, which in general would result in the degradation of the cargo. The students working in this project, which combines biochemical, physical, and synthetic chemistry, will gain experience and interdisciplinary learning, and these students will be engaging in creating high quality on-line and freely available science oriented and web-based comic strips aimed at K-12 students. These comic strips will be used to promote scientific literacy, and to encourage students and their parents to engage and discuss the ideas and concepts emerging from contemporary research. To that end, the project will take advantage of the unique diversity available at the campus to create multi-lingual comics to engage people from all over the world in the research that is being funded through this award.