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 vector.However,the applications of nonviral vectors are still suffering from the limits of the low drug loading efficiency and/or the low gene transfection efficiency.Herein,a novel carrier-free nanodrug-based virus-surface-mimicking gene delivery nanosystems is designed by condensing the 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(97.5%)characteristics to PEI/DNA nanosystem.Meanwhile,the gene transfection efficiency of DNA can also be enhanced for the 4-fold increased roughness of coated DNPs.The in vitro and in vivo results demonstrate that a rough surface of the carrier-free nanodrug-based gene delivery nanosystems can enhance the endocytosis of the nanoparticles in many cell lines,especially 7-fold improvement in HeLa cells.Consequently,enhance the chemo/gene co-therapy of the cancers.It is the first time to use soft materials to design virus-surfacemimicking nanocarriers,avoiding the side effects of inorganic materials caused by their non-degradable property.Importantly,our delicate design opens a new pathway to develop a nature-inspired nanoparticle for cancer synergistic therapy.