Targeted delivery of anti-cancer drugs by MS2 virus-like particles

摘要: Problems associated with poor pharmacokinetics and biodistribution, as well toxic off-target effects, limit the curative potential of most anti-cancer drugs. This has prompted development nanoparticulate drug delivery systems to impart both more favourable pharmacological properties precise tumour targeting. The vast number formulations, ranging from fully synthetic ones derived natural sources, currently undergoing clinical trials or preclinical testing underlines significance this field. project is a proof-of-concept investigation into feasibility effectiveness novel system, based on virus-like particles (VLPs) MS2 bacteriophage. Doxorubicin (Dox) an anti-BCL2 siRNA were used model cargos. They packaged inside VLPs either by chemical infusion, via covalent attachment packaging signal, TR, respectively. An average loading ~10 molecules ~110 Dox per VLP was achieved. Packaged cargos remained stably encapsidated; protected nuclease degradation. surface decorated polyethylene glycol (PEG), tumour-targeting ligands, human transferrin (Tf) A9L, RNA aptamer that targets prostate-specific membrane antigen (PSMA). Extensive PEGylation achieved (~97% coat proteins), each displayed ~7 Tf ~16 A9L. PEGylation significantly reduced non-specific cellular uptake VLPs, antibody binding. Further addition ligands facilitated specific targeted cancer cells in culture, likely receptor-mediated endocytosis, induced significant cytotoxicity LC50 nM for ~800 Dox. Importantly, negligible effects observed presence excess free targeting non-targeted control cell lines. Furthermore, did not appear induce any effects. MS2 continue show promise robust, flexible effective system. highlights versatility displaying range useful their surface, various therapeutic cargos, demonstrated ability specifically deliver drugs cells. Though further studies are required, work presented here important step towards realising