Dong, Fangyi2021-04-122021-04-122021-01https://hdl.handle.net/11299/219281University of Minnesota M.S. thesis. January 2021. Major: Pharmaceutics. Advisors: Jayanth Panyam , Timothy Wiedmann. 1 computer file (PDF); v, 30 pages.Imiquimod is a Toll-like receptor 7 (TLR7) agonist approved for treating genital warts and actinic keratoses and has demonstrated promise as an anticancer vaccine adjuvant. However, as a small molecule, imiquimod suffers from poor pharmacokinetic properties that result in sub-optimal therapeutic activity and raise the risk of systemic side effects. Delivery systems such as nanoparticles could help improve the delivery of imiquimod to the target site and avoid undesirable side effects. Mesoporous silica nanoparticles (MSN) possess excellent chemical stability, high drug loading capacity, and a size range appropriate for imiquimod delivery. However, the inert nature of -Si-O – bonds in MSN limits its biodegradability. Previous studies have reported that doping manganese (Mn) ions endow acidic pH responsive degradation and drug release from MSN. Since TLR7 is located in the acidic endosomes of dendritic cells, pH responsiveness could significantly improve immune response and mitigate side effects of imiquimod. In the current study, PEGylated manganese doped silica nanoparticles (PEG-MnMSN) demonstrated good biocompatibility and excellent (41.96%) imiquimod encapsulation efficiency. The PEG-MnMSN also showed pH-responsive drug release, with a greater fraction of the encapsulated drug released in acidic pH (5.5) than at physiologic pH (7.4). Overall, our studies suggest PEG-MnMSN’s have exciting potential as a carrier for imiquimod-based cancer immunotherapy.enManganesenanoparticlesilicaTLR7Thesis or Dissertation