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Induction of Immunogenic Cell Death in Breast Cancer by Conductive Polymer Nanoparticle-Mediated Photothermal Therapy

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journal contribution
posted on 09.11.2020, 18:05 by Madeline Elaine Huff, Fatma Özge Gökmen, Jessica S. Barrera, Emilio J. Lara, James Tunnell, Jennifer Irvin, Tania Betancourt
Emerging research in cancer immunotherapies has pointed toward the need for companion therapies that lead to immunogenic cell death. Photothermal therapy (PTT) can not only cause cancer cell death but also cause the release of tumor-specific antigens and damage-associated molecular patterns (DAMPs), which act as adjuvants. In this work, conductive polymer nanoparticles (NPs) of poly­(3,4-ethylenedioxythiophene) (PEDOT) were studied as PTT agents and their ability to mediate immunogenic cell death was investigated. The spherical, ∼40 nm NPs presented strong absorption of light between 700 and 900 nm. Their chemical composition was confirmed by FTIR and elemental analysis, while their amorphous morphology was confirmed by X-ray diffraction. NP internalization into MDA-MB-231 cells was observed within 4 h of incubation. At 500 μg/mL, the NPs were found to cause an increase in temperature of about 32 °C from the baseline upon irradiation with an 808 nm laser. This temperature increase proved to be sufficient to cause cell death after 5–15 min of laser irradiation at 3 W/cm2. Cell death upon NP-mediated PTT occurred mainly through apoptosis after 1.5, 6, and 12 h of exposure of the cells to the NPs, while longer exposure periods led primarily to cell necrosis. Our studies also demonstrate that PEDOT NP-mediated PTT induced presentation of DAMPs. Specifically, increased calreticulin translocation to the cell membrane, increased surface HMGB1 expression on nonpermeabilized cells, increased cytosolic HMGB1 presence in permeabilized cells, and decreased internal ATP were observed in cells that were exposed to increased thermal doses. The highest DAMP presentation levels were observed in cells treated with 500 μg/mL PEDOT NPs and irradiated for 5 and 15 min, which resulted in a maximum cell temperature of 65–68 °C. PTT with PEDOT NPs enable specific eradication of cancer cells via immunogenic cell death, thereby showing potential as agents for modulation of tumor immunogenicity.