Asymmetric Silica Nanoparticles with Tailored Spiky Coverage Derived from Silica-Polymer Cooperative Assembly for Enhanced Hemocompatibility and Gene Delivery.

Asymmetric mesoporous silica nanoparticles (AMSNs) with one side featuring a spiky nanotopography, while the other side is smooth and solid, were synthesized via an ethylenediamine (EDA)-directed silica-polymer cooperative assembly approach. By simply varying the EDA amount (), AMSNs- samples with adjustable spiky surface coverage were obtained. It is demonstrated that a spiky coverage higher than 50% improved the hemocompatibility of AMSN-, possibly due to the reduced contact area of the smooth side exposed to the red blood cell (RBC) membrane. Moreover, AMSNs- and AMSNs- with high spiky coverage enhanced their plasmid DNA (pDNA) loading and binding capability, as well as cellular uptake into HEK-293T cells, thus resulting in high transfection performance. The good hemocompatibility and high performance in pDNA delivery of AMSNs- with high spiky coverage allow them to serve as promising nonviral vectors for potential applications in gene therapies and DNA vaccines.