Aim: Plant virus-like particles (VLPs) have emerged as a novel platform for delivery of drugs/antibodies. The aim of the present investigation is to establish the entry mechanism of flexuous rod-shaped virus particles into mammalian cells. Methods: Far-Western blot analysis, pull-down and ELISA were used to characterize vimentin and Hsp60 interaction with VLPs. The mode/kinetics of internalization of VLPs was deciphered using pharmacological inhibitors/endosomal markers. Results & discussion: The flexuous rod-shaped VLPs of Pepper vein banding virus (PVBV) enter HeLa and HepG2 cells via cell-surface proteins: vimentin and Hsp60, respectively. VLPs internalize via different modes of endocytosis in HeLa, HepG2 cells and are biodegradable. Vimentin and Hsp60 could be potential epithelial ligands that facilitate targeting of nanoparticles to tumor cells.
Background: Anti-tau immunotherapies targeting phospho-epitopes have shown promising outcome in pre-clinical studies, although, with certain limitations in terms of mode of antibody delivery and concentration of antibodies required to obtain positive outcome.
Results & methods:In this study, virus-like particles containing 180 binding sites for antibodies per particle was chosen as the antibody delivery tool. Antibodies against phospho-tau-peptide (sequence 50-71 AA) phosphorylated at S68, T69, and T71 were coated onto chimeric Sesbania mosaic virus-like nanoparticles containing B domain from S. aureus (SLB). SLB bound antibodies showed enhanced binding to tau protein as compared to unconjugated antibodies. Passive immunization studies were conducted in okadaic acid (OKA) induced tauopathy model rats. In Barnes maze task, SLB-Ab treated rats exhibited marked learning ability in comparison to OKA rats, with progressive decrease in the number of errors made and the time taken in reaching the escape hole.Conclusions: These results suggest the merits of SLB-Ab in improving spatial memory as reflected by far lesser number of SLB-Ab injections required to observe the therapeutic effect.
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