Worm-Like Biomimetic Nanoerythrocyte Carrying siRNA for Melanoma Gene Therapy

A major challenge in siRNA vectors is developing approaches that ensure that when administered in vivo, the vectors can target their requisite site of action. This study reports a third type of nanoworm, biomimetic nanoerythrocytes for siRNA delivery, except for filomicelle and nanoworm iron-oxide particle, which is the first approach that allows for targeted siRNA delivery by a process involving red blood cell (RBC) membrane cloaking of charge-reversible polyplexes of siRNA and polycation. RBC membrane cloaking protects siRNA from RNase A degradation. Moreover, the RBC membrane-cloaked charge-reversible siRNA vector (RBC-reversible polyplex (RP)) not only stays longer in the blood circulation than that of negatively charged bovine serum albumin (BSA) spheres and positively charged BSA, but is also able to escape from late endosomes/lysosomes, to achieve effective transfection for gene knockdown. The knockdown result in vivo is remarkably consistent with that of intracellular trafficking and transfection in vitro. Due to the outstanding biocompatibility and active targeting (cRGD), the 7 mg kg^-1 dose siSurvivin in RGD-RBC-RP exhibits obviously superior anticancer effects at the animal level after two weeks. Therefore, the biomimetic worm-like nanoerythrocyte charge-reversible gene vector is a new and general method for highly efficient siRNA therapy in vivo.