Drug Delivery

Porous Silicon Nanoparticles for Drug Delivery

Porous Silicon Nanoparticle Therapeutics (Collaboration with Duvall Group)

Porous silicon nanoparticles (PSNPs) are excellent vehicles to improve delivery of drugs owing to their high porosity, large internal surface area and biocompatibility. In particular, our group is interested in using PSNPs to enhance the delivery and therapeutic efficacy of novel nucleic-acid drugs known as peptide nucleic acids (PNA). PNA have demonstrated enormous potential in treating a wide array of diseases (including viral infections, central nervous system disorders, cardiovascular disease, and cancer), but PNA therapeutic activity is limited by poor bioavailability and low-levels of cellular uptake. Our hypothesis is that the targeted delivery and therapeutic activity of PNA can be increased by packaging PNA into PSNP delivery vehicles.

Our initial studies show that PNA therapeutics can be synthesized in situ within a PSi substrate to yield therapeutic-loaded PSNPs. These arbitrarily shaped PSNPs significantly enhanced PNA intracellular uptake, were shown to be non-toxic, and ultimately improve PNA therapeutic efficacy. In addition, we have shown that Direct Imprinting of Porous Substrates (DIPS) can be used to size and shape-engineer PSNPs. Current studies are focused on examining the effect of PSNP geometry on the enhance delivery and cellular uptake of therapeutic PNA.

KRB1

(Left) Cartoon describing in situ synthesis of PNA in PSi, a process used to fabricate PNA-loaded PSNPs, or “PNA-PSNPs.” (Right) PSNPs enhance the intracellular delivery of PNA therapeutics, which otherwise do not enter the cell.

KRB2

(Left) PSNPs are more biocompatible than the positive control(green), and (Right) significantly enhance PNA therapeutic activity, as measured by % increase in luciferase activity in Huh7 human hepatocarcinoma cells. (*Note “AMO” references the positive control therapeutic oligonucleotide that was delivered with Fugene 6 transfection reagent; luciferase activity measured 48hrs after treatment)

KRB3

(above) Examples of possible PSNP geometries produced by DIPS.