期刊
JOURNAL OF CONTROLLED RELEASE
卷 172, 期 2, 页码 568-578出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.04.023
关键词
Viral nanoparticle; Drug delivery; Cowpea mosaic virus; Infusion
资金
- NIH [NIBIB R00 EB009105]
- NCI [R25 CA148052]
- Mt. Sinai Foundation
This work is focused on the development of a plant virus-based carrier system for cargo delivery, specifically 30 nm-sized cowpea mosaic virus (CPMV). Whereas previous reports described the engineering of CPMV through genetic or chemical modification, we report a non-covalent infusion technique that facilitates efficient cargo loading. Infusion and retention of 130-155 fluorescent dye molecules per CPMV using DAPI (4 ',6-diamidino-2-phenylindole dihydrochloride), propidium iodide (3,8-diamino-5-[3-(diethylmethylammonio) propyl]-6-phenylphenanthridinium diiodide), and acridine orange (3,6-bis(dimethylamino) acridinium chloride), as well as 140 copies of therapeutic payload proflavine (PF, acridine-3,6-diamine hydrochloride), is reported. Loading is achieved through interaction of the cargo with the CPMV's encapsidated RNA molecules. The loading mechanism is specific; empty RNA-free eCPMV nanoparticles could not be loaded. Cargo-infused CPMV nanoparticles remain chemically active, and surface lysine residues were covalent modified with dyes leading to the development of dual-functional CPMV carrier systems. We demonstrate cargo-delivery to a panel of cancer cells (cervical, breast, and colon): CPMV nanoparticles enter cells via the surface marker vimentin, the nanoparticles target the endolysosome, where the carrier is degraded and the cargo is released allowing imaging and/or cell killing. In conclusion, we demonstrate cargo-infusion and delivery to cells; the methods discussed provide a useful means for functionalization of CPMV toward its application as drug and/or contrast agent delivery vehicle. (C) 2013 Elsevier B.V. All rights reserved.
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