Targeting therapies and imaging agents specifically to areas of disease in the body, while avoiding healthy tissue, is an important goal in biomedicine. This project focuses on the utilization of the well-characterized plant virus Cowpea mosaic virus (CPMV) as a platform for the design of novel """"""""smart"""""""" targeted therapeutics. CPMV particles are naturally occurring, monodisperse, 30 nm-sized nanoparticles. The combined biodegradability, ease of production, and tunability make CPMV an excellent candidate for such platform development. The utility of multivalent fluorescent CPMV probes for vascular imaging in live animals has been demonstrated. More recently, we showed tumor homing of specifically targeted CPMV particles in preclinical animal models. The overall goal of this proposal is the development of 'smart'3D nanodevices that interlink targeting. Imaging, and therapy. The first goal is to explore the potential of therapeutic CPMV formulations. I will use VNPs as a template for the constrained synthesis of iron oxide nanocrystals within the capsld interior for potential applications in hyperthermia treatment. Next, I will evaluate VNP-photosensitizer (fullerene) hybrid materials for photo-activated cancer therapy. In the second goal, to combine targeting, imaging, and therapy, will fabricate highly organized, controllable, and tunable VNPs networks consisting of various different """"""""specialized"""""""" VNPs. Such complex formulations are expected to overcome limitations of single VNPs and would allow i) targeting to several molecular receptors thus increasing tumor homing efficiency, and ii) delivery of different therapeutics, which is expected to increase therapeutic success. Cancer is a complex endeavor and i stronly believe that such multicomponent formulations may serve as promising candidates for novel targeted therapies. During my pre-doctoral training 1 have learned to tailor VNPs and to fabricate nanostructured matenals. My post-doctoral training has provided expertise in in vitro and in vivo models. This puts me in a unique position of being able to create nanomaterials, but also to study their in vivo properties.

Public Health Relevance

Cancer is causing substantial death and disabilities all over the world. Chemotherapy is generally not targeted and therefore many adverse side effects occur. Specifically targeted therapies would increase efficiency and result in fewer side effects, and thus improve quality of life. This project will help to understand how to build a complex network that combines targeting and therapy in a single formulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Transition Award (R00)
Project #
5R00EB009105-05
Application #
8322654
Study Section
Special Emphasis Panel (NSS)
Program Officer
Peterson, Karen P
Project Start
2009-08-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$237,248
Indirect Cost
$64,713
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Cho, Choi-Fong; Shukla, Sourabh; Simpson, Emily J et al. (2014) Molecular targeted viral nanoparticles as tools for imaging cancer. Methods Mol Biol 1108:211-30
Yildiz, Ibrahim; Lee, Karin L; Chen, Kevin et al. (2013) Infusion of imaging and therapeutic molecules into the plant virus-based carrier cowpea mosaic virus: cargo-loading and delivery. J Control Release 172:568-78
Lee, Karin L; Hubbard, Logan C; Hern, Stephen et al. (2013) Shape matters: the diffusion rates of TMV rods and CPMV icosahedrons in a spheroid model of extracellular matrix are distinct. Biomater Sci 1:
Aljabali, Alaa A A; Shukla, Sourabh; Lomonossoff, George P et al. (2013) CPMV-DOX delivers. Mol Pharm 10:3-10
Shukla, Sourabh; Ablack, Amber L; Wen, Amy M et al. (2013) Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle Potato virus X. Mol Pharm 10:33-42
Wen, Amy M; Rambhia, Pooja H; French, Roger H et al. (2013) Design rules for nanomedical engineering: from physical virology to the applications of virus-based materials in medicine. J Biol Phys 39:301-25
Wen, Amy M; Lee, Karin L; Yildiz, Ibrahim et al. (2012) Viral nanoparticles for in vivo tumor imaging. J Vis Exp :e4352
Wen, Amy M; Ryan, Mary J; Yang, Alice C et al. (2012) Photodynamic activity of viral nanoparticles conjugated with C60. Chem Commun (Camb) 48:9044-6
Yildiz, Ibrahim; Tsvetkova, Irina; Wen, Amy M et al. (2012) Engineering of Brome mosaic virus for biomedical applications. RSC Adv 2:3670-3677
Wen, Amy M; Shukla, Sourabh; Saxena, Pooja et al. (2012) Interior engineering of a viral nanoparticle and its tumor homing properties. Biomacromolecules 13:3990-4001

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