Mitochondrial dysfunction is a key component of various human diseases, including cancer, obesity, diabetes and various neurodegenerative diseases. Efficient treatment is hindered by poor understanding of how the chemical moieties of delivery vehicles affect the material fate and distribution within the cell. Conjugated polymer nanoparticles (CPNs) are multifunctional materials that have received significant attention for intracellular sensing, labeling, and delivery. Because of their fluorescent nature, CPNs provide the ideal platform to study how structural changes affect the material fate within the cell. Recently, we demonstrated how side chain and backbone structures of CPNs affect toxicity and subcellular localization of the internalized material.  Here we report a series of triphenyl phosphonium(TPP)-containing CPNs and the effect of varying side-chain and conjugated backbone modifications on the cellular toxicity and intracellular fate of the material. A series of CPNs was synthesized from a suite of TPP-containing homo- and co-polymers containing methoxide or ethylene oxide (EO) alternating units as well as a biodegradable backbone linker. Materials were characterized using UV-Visible, fluorescence, infrared (IR) and proton nuclear magnetic resonance spectroscopy (<sup>1</sup>H NMR). Endosomal and mitochondrial uptake and cellular toxicity were measured after 18 hours of CPN incubation with human cervical cancer (HeLa) cells. We found a significant difference in mitochondrial and endosomal co-localization between the methoxide-containing and EO-containing TPP-CPN. Additionally, incorporation of a biodegradable linker further modulated the CPN fate within the cell. In conclusion, through the excellent fluorescent nature of CPNs we were able to monitor how side-chain and backbone modifications affected the cellular fate of the material. The observed tunability of physicochemical properties and the related biophysical properties make CPNs a promising platform for labelling, monitoring, and delivery of therapeutic substances to biological targets.<br/>This work has been supported by NIH (SC1GM092778) and in part by NIH/NIGMS-RISE (R25 GM61347;EM).

Cellular toxicity and uptake behavior of triphenyl phosphonium-containing conjugated polymer nanoparticles

249th National Meeting (2015)

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