Journal
JOURNAL OF CONTROLLED RELEASE
Volume 231, Issue -, Pages 103-113Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.02.045
Keywords
Drug delivery; Tobacco mosaic virus; Nanoparticles; Nanorods; Breast cancer
Funding
- NCATS NIH HHS [UL1 TR000439] Funding Source: Medline
- NHLBI NIH HHS [T32 HL105338] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007250] Funding Source: Medline
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Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300 x 18 nm with a 4 nm-wide central channel. Heat-transformation can be applied to TMV yielding spherical nanoparticles (SNPs) measuring similar to 50 nm in size. While bioconjugate chemistries have been established to modify the TMV rod, such methods have not yet been described for the SNP platform. In this work, we probed the reactivity of SNPs toward bioconjugate reactions targeting lysine, glutamine/aspartic acid, and cysteine residues. We demonstrate functionalization of SNPs using these chemistries yielding efficient payload conjugation. In addition to covalent labeling techniques, we developed encapsulation techniques, where the cargo is loaded into the SNP during heat-transition from rod-to-sphere. Finally, we developed TMV and SNP formulations loaded with the chemotherapeutic doxorubicin, and we demonstrate the application of TMV rods and spheres for chemotherapy delivery targeting breast cancer. (C) 2016 Elsevier B.V. All rights reserved.
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