UC San Diego

There is increased interest in porous silicon nanomaterials for biomedical applications due to their biodegradability, their biocompatibility, and their intrinsic photoluminescence. This thesis describes cargo loading chemistry, surface chemistry, molecularly targeted delivery and bioimaging applications using porous silicon nanomaterials.

After a brief introduction to porous silicon materials for biomedical applications, Chapter 2 describes a single-step procedure to simultaneously load and protect a model siRNA therapeutic in porous silicon nanoparticles (pSiNPs). Exogenous calcium ions precipitate with locally generated silicic acid to form calcium silicate, which serves to encapsulate the siRNA payload in pSiNPs. The target gene knockdown efficiency in vitro and target tissue accumulation of delivered siRNA in vivo are demonstrated.

Chapter 3 presents a facile chemical modification of the surface of the hydroxylated silicon nanostructure. The reaction, a ring-opening heterocyclic silane “click” reaction, is a rapid and efficient means to obtain high surface coverage while preserving the open pore structure and intrinsic photoluminescence of the original silicon nanostructure. This chemistry is sufficiently mild to maintain the activity of payload proteins.

Chapter 4 presents the example of pSiNPs as an imaging agent, which are targeted to tumor tissues in vivo using an iRGD peptide targeting probe, and the nanoparticles are imaged by two-photon microscopy. Superior photostability and low systemic toxicity are observed.

Chapter 5 discusses enhanced photoacoustic signals that can be obtained from indocyanine green (ICG) when it is encapsulated in pSiNPs. The photoacoustic response from ICG is enhanced 17-fold when it is sealed in pSiNPs. The substantially improved performance is attributed to the low thermal conductivity of pSiNPs and their ability to protect loaded ICG from photolytic degradation.