Carrier-free nanodrug-based virus-surface-mimicking nanosystems for efficient drug/gene co-delivery

Nature-inspired nanoparticles, from pathogens to mammalian cells, have attracted increasing attention, for their specific functions and unparalled features that are often desired in designing drug/gene delivery nonviral vectors. However, the applications of nonviral vectors are still suffering from the limits of low drug loading efficiency and/or low gene transfection efficiency. Herein, a novel carrier-free nanodrug-based virus-surface-mimicking gene delivery nanosystem is designed by condensing doxorubicin nanoparticles (DNPs) onto the surface of the PEI/DNA nanocomplex through electrostatic force, which would prolong the blood circulation time of PEI/DNA and confer high drug loading characteristics to the PEI/DNA nanosystem. Meanwhile, the gene transfection efficiency of DNA can also be enhanced for the increased roughness of coated DNPs. The in vitro and in vivo results demonstrate that carrier-free nanodrug-based gene delivery nanosystems with high drug loading efficiency (97.5%) as well as a rough surface can enhance the endocytosis of the nanoparticles, and consequently enhance the chemo/gene co-therapy of cancers. This is the first time soft materials are used to design virus-surface-mimicking nanocarriers, avoiding the side effects of inorganic materials caused by their non-degradable property. Importantly, our delicate design opens a new pathway to develop nature-inspired nanoparticles for cancer synergistic therapy.