The delivery of biomolecules, including therapeutic drugs, genes and proteins, provides a promising vehicle for the treatment of many incurable diseases. Efficient delivery of biomolecules remains a technical challenge due to poor targeting and delivery efficiency. The use of viral-, liposome-, and nanotube-mediated techniques for the delivery of biomolecules has been hindered by their cytotoxicity, low efficiency and poor biocompatibility properties. Delivery mechanisms that utilize cell culture substrates, such as nanowire-grafted surfaces, have recently gained traction as a promising method for drug delivery. However, the use of nanowire-based delivery substrates require the cells to be pre-coated with biomolecules, preventing repeated doses or sequential combination of therapies. The invention disclosed here utilizes a novel nanowire-based delivery approach capable of achieving efficiency rates greater than 90%.

• High efficiency (>90%) of the transfection of encapsulated SNPs
• No need to pre-coat substrate with biomolecules, therefore allowing multiple doses to be administered
• Improved delivery in difficult-to-transfect cell lines

• This platform can be applied to the delivery of assorted biomolecules including genes, proteins, RNA species, drugs and reporters
• Possibility to re-engineer the CDNS/SNP recognition motifs generating a robust platform

Researchers in the laboratory of Dr. Hsian-Rong Tseng at UCLA have utilized a nanowire grafted substrate for the delivery of biomolecules. The surface of the nanowire substrate has been coated with a particular molecular recognition motif, referred to as a catalytic delivery nanosubstrate (CDNS), which enables delivery of the biomolecules into the cell of interest. The binding partner of the CDNS recognition motif is coated on a supramolecular nanoparticle (SNP) that houses the biomolecule to be delivered. The CDNS serves to concentrate SNPs from the cell culture medium onto the nanosubstrate and enhances local topological interactions between the SNP and the cell to improve biomolecule delivery. Utilization of the CDNS and SNP in combination significantly increases delivery efficiency compared to just SNPs alone. This technology provides a platform for the delivery of diverse biomolecules with high efficiency in a wide range of cells that are difficult to transfect including primary cells, stem cells, neuronal cells and immune cells.