Ultra-Small Nanoparticle-Based Platform for Photodynamic Skin Cancer Therapy

Medicine can benefit significantly from advances in nanotechnology because nanoscale assemblies promise to improve on previously established diagnostic and therapeutic regimes on account of improved delivery. Non-melanoma skin cancer (NMSC) is the most common cancer and is associated with considerable morbidity. Intervention for NMSC is largely surgical, and an effective, tissue-salvaging therapeutic for NMSC is a significant unmet need. Photodynamic therapy (PDT) is one of the few currently available non-invasive approaches to treat NMSC, but depends on the uptake of protoporphyrin IX (PphIX), a naturally occurring porphyrin constituent of heme and a popular photosensitizer that can selectively accumulate in cancer cells. Owing to the low bioavailability of PphIX, improved delivery techniques are needed to promote PphIX accumulation at the tumor site. Recently, we have developed ultra-small silica nanoparticles (~10 nm) capable of serving as nanocarriers. The main objective of this proposed research is to employ ultra-small silica nanoparticles as nanocarriers for targeted PphIX delivery into NMSCs for photodynamic skin cancer therapy. Specifically, we will: i) investigate the toxicology and stability of the polyethylene glycol-conjugated nanoparticles to ensure good biocompatibility; ii) trace the metabolic pathway of the silica nanoparticles, with the expectation that the ultra-small nanoparticles will be cleared within days; iii) evaluate the ability of PphIX-conjugated nanoparticles to accumulate in cancer (vs. primary normal) cells; and iv) determine the efficacy of the PDT-activated PphIX-conjugated nanoparticles in killing cancer cells. The proposed project will not only develop ultra-small silica nanoparticles as photosensitizer nanocarriers with enhanced biocompatibility and performance, but will also provide an in-depth understanding for the roles of size and surface functionality in the metabolism of these nanoparticles. Ultimately, this project will provide an innovative therapeutic platform that can simultaneously target skin cancer cells, enable the location to be imaged by optical methods, and carry out efficient PDT to inhibit the tumor cell growth. Should this highly translational project be successful, the study will move towards pre-clinical trial application.