Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer

JOURNAL OF CONTROLLED RELEASE

卷:231

Article; Proceedings Paper

Bruckman, Michael A.¹  Czapar, Anna E.²  VanMeter, Allen¹  Randolph, Lauren N.¹  Steinmetz, Nicole F.^1,3,4,5 

[1] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Dept Mat Sci & Engn, Cleveland, OH 44106 USA

[5] Case Western Reserve Univ, Dept Macromol Sci & Engn, Cleveland, OH 44106 USA

关键词: Drug delivery;    Tobacco mosaic virus;    Nanoparticles;    Nanorods;    Breast cancer;   

DOI  :  10.1016/j.jconrel.2016.02.045

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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