Nanoparticles for Biomedical Applications: Photothermal Therapy and Nuclear Delivery.

Abstract

Cancer is still a grand challenge faced by society today. Nanomedicine addresses many of the serious issues associated with conventional treatments. Nanoparticles (NPs) are advantageous for therapy because they are minimally invasive, have tunable characteristics and can be used as targeted and multifunctional treatment platforms. This thesis focuses on the use of both polymeric and gold NPs for photothermal therapy (PTT) of cancer cells, and describes the surface engineering of gold NPs for optimized, cell specific nuclear delivery. The first ever use of the FDA approved Coomassie Brilliant blue (CB) dye as a photosensitizer for PTT of cancer is detailed. The CB dye is covalently linked into the matrix of biologically compatible, hydrogel NPs. Also, a portable, inexpensive, low intensity LED is used as the light source. Incubation with moderate NP concentrations, combined with relatively low light levels, yielded nearly complete cell death within 3 hours of treatment. Another part of this dissertation research describes the stepwise surface engineering of specialty gold NPs for optimized delivery to cancer cell nuclei. These femtosecond laser ablation generated gold NPs have virgin surfaces to which cell-specific and nucleus-specific targeting peptides are directly attached. Efficient nuclear delivery was achieved using as little as 100pM of NPs solution, a concentration that is at least an order of magnitude lower than what has been previously reported in nuclear delivery studies involving gold NPs. The aforementioned nuclear-targeted gold NPs were also successfully utilized for PTT of cancer cells in vitro. A drastic difference in treatment efficacy was observed when the therapy was mediated by gold NPs delivered into the nucleus compared to when the NPs remained outside the nucleus. In the former case, the cell viability drops dramatically at early times and complete cell death is observed at six hours post-treatment. In the latter case, the viability decreases slowly over time and a maximum change of approximately 50% is observed 12 hours post-treatment. Overall this thesis provides several contributions to the field of Nanobiotechnology, through the presentation of highly effective, nanoparticle-mediated PTT. The latter can be easily incorporated into a multimodal approach for the treatment of cancer.