IONIC NANOMEDICINE STRATEGY TO DEVELOP EFFECTIVE CHEMO-PTT COMBINATION CANCER THERAPEUTICS

Mujeebat Bashiru, Mavis Forson, Arisha Ishtiaq, Adeniyi Oyebade, Samantha Macchi, Shehzad Sayyed, Nawab Ali, Robert J. Griffin, Adegboyega K. Oyelere and Noureen Siraj*

Herein, a detailed investigation of nanodrugs derived by combining a chemotherapy (chemo) and photothermal therapy (PTT) approaches to enhance chemo drug efficacy is presented. Tamoxifen and its metabolite; N-desmethyltamoxifen are the selected chemo drugs that were electrostatically attached with a PTT agent, NaIR820, via a metathesis approach to develop two different ionic material (IM)-based chemo-PTT drugs. Ionic nanomaterials (INMs) were synthesized using reprecipitation method, and these carrier- free nanoparticles were characterized in detail. Photophysical properties of NaIR820 parent compound, and their derived chemo-PTT IMs and INMs revealed significant alterations in absorption and fluorescence emission spectra of IR820. Photophysical results demonstrated that INMs exhibited promising characteristics as photothermal agents that are beneficial for light mediated therapy. Photothermal conversion efficiency and reactive oxygen quantum yield of INMs and IMs also improved significantly in comparison to the parent NaIR820 compound. In vitro cell viability studies demonstrated improved dark and light cytotoxicity of chemo-PTT INMs as compared to treatments that involved either the mixture of both soluble parent drugs and chemo or PTT drugs independently. Moreso, apoptotic cell death signal was greatly enhanced for the INMs as opposed to the parent chemo drugs.