Virus-like particles: Next-generation nanoparticles for targeted therapeutic delivery.

Most drug therapies distribute the agents throughout the entire body, even though the drugs are typically only needed at specific tissues. This often limits dosage and causes discomfort and harmful side-effects. Significant research has examined nanoparticles (NPs) for use as targeted delivery vehicles for therapeutic cargo, however, major clinical success has been limited. Current work focuses mainly on liposomal and polymer-based NPs, but emerging research is exploring the engineering of viral capsids as noninfectious protein-based NPs-termed virus-like particles (VLPs). This review covers the research that has been performed thus far and outlines the potential for these VLPs to become highly effective delivery vehicles that overcome the many challenges encountered for targeted delivery of therapeutic cargo.

Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in Caenorhabditis elegans.

Efficient clearance of apoptotic cells by phagocytes is important for development, tissue homeostasis, and the prevention of autoimmune responses. Phagosomes containing apoptotic cells undergo acidification and mature from Rab5-positive early to Rab7-positive late stages. Phagosomes finally fuse with lysosomes to form phagolysosomes, which degrade apoptotic cells; however, the molecular mechanism underlying phagosome-lysosome fusion is not fully understood. Here we show that the Caenorhabditis elegans Arf-like small GTPase Arl8 (ARL-8) is involved in phagolysosome formation and is required for the efficient removal of apoptotic cells. Loss of function of arl-8 results in the accumulation of apoptotic germ cells. Both the engulfment of the apoptotic cells by surrounding somatic sheath cells and the phagosomal maturation from RAB-5- to RAB-7-positive stages occur in arl-8 mutants. However, the phagosomes fail to fuse with lysosomes in the arl-8 mutants, leading to the accumulation of RAB-7-positive phagosomes and the delayed degradation of apoptotic cells. ARL-8 localizes primarily to lysosomes and physically interacts with the homotypic fusion and protein sorting complex component VPS-41. Collectively our findings reveal that ARL-8 facilitates apoptotic cell removal in vivo by mediating phagosome-lysosome fusion during phagocytosis.