Journal
MOLECULAR PHARMACEUTICS
Volume 10, Issue 1, Pages 26-32Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp300238w
Keywords
cowpea mosaic virus (CPMV); endocytosis; entry; caveolae; macropinocytosis; clathrin; Rab5; Rab11
Funding
- UCSD Neuroscience Microscopy facility [P30 NS047101]
- National Institutes of Health [R01CA112075]
- American Heart Association
- NATIONAL CANCER INSTITUTE [R01CA112075] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P30NS047101] Funding Source: NIH RePORTER
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Cowpea mosaic virus (CPMV) has been used as a nanoparticle platform for biomedical applications including vaccine development, in vivo vascular imaging, and tissue-targeted delivery. A better understanding of the mechanisms of CPMV targeting and cell internalization would enable enhanced targeting and more effective delivery. Previous studies showed that, following binding and internalization by mammalian cells, CPMV localizes in a perinuclear late-endosome compartment where it remains for as long as several days. To further investigate endocytic trafficking of CPMV within the cell, we used multiple approaches including pharmacologic inhibition of pathways and colocalization with endocytic vesicle compartments. CPMV internalization was clathrin-independent and utilized a combination of caveolar endocytosis and macropinocytosis pathways for entry. CPMV particles colocalized with Rab5(+) early endosomes to traffic ultimately to a lysosomal compartment. These studies facilitate the further development of effective intracellular drug-delivery strategies using CPMV.
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