Synthesis and Electropolymerization of 3,5-Bis-(3,4-ethylenedioxythien-2-yl)-4,4-dimethyl Isopyrazole: A Donor-Acceptor-Donor Monomer

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 tumorspecific 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 Xray 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/cm 2 . 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.

show abstract

“…The monomer was purified as previously described . 3,4-Ethylenedioxythiophene was dissolved in a large excess of dichloromethane.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…The monomer was purified as previously described. 22 3,4-Ethylenedioxythiophene was dissolved in a large excess of dichloromethane. The solution was then extracted with 0.1 M HCl, using equal parts of 0.1 M HCl to dichloromethane, using a separatory funnel under a fume hood.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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

Huff

Gökmen

Barrera

et al. 2020

ACS Appl. Polym. Mater.

View full text Add to dashboard Cite

show abstract

“…21 EDOT was first lithiated at −78°C, followed by transmetallation with ZnCl 2 at 0°C. EDOT-ZnCl was then coupled to the precursor diethyl 4,4′-[(2,5-dibromo-1,4-phenylene)bis(oxy)]dibutanoate by Negishi coupling and refluxed for 4 days.…”

Section: Monomer Synthesismentioning

confidence: 99%

Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation

Cantu¹,

Walsh²,

Pattani³

et al. 2017

IJN

View full text Add to dashboard Cite

“…Purify EDOT as described previously. 25 2. Recrystallize tetrabutyl ammonium perchlorate (TBAP) from ethyl acetate and dry under vacuum for 24 hr.…”

Section: Monomer Synthesismentioning

confidence: 99%

Electroactive Polymer Nanoparticles Exhibiting Photothermal Properties

Cantu

Rodier

Iszard

et al. 2016

JoVE

View full text Add to dashboard Cite

A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).

show abstract

Synthesis and Electropolymerization of 3,5-Bis-(3,4-ethylenedioxythien-2-yl)-4,4-dimethyl Isopyrazole: A Donor-Acceptor-Donor Monomer

Cited by 8 publications

References 21 publications

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

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

Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation

Electroactive Polymer Nanoparticles Exhibiting Photothermal Properties

Contact Info

Product

Resources

About