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

Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4′-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene] bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies (~50%), that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy.

[1]  Qiushi Ren,et al.  Uniform Polypyrrole Nanoparticles with High Photothermal Conversion Efficiency for Photothermal Ablation of Cancer Cells , 2013, Advanced materials.

[2]  D. M. Morgan,et al.  Tetrazolium (MTT) assay for cellular viability and activity. , 1998, Methods in molecular biology.

[3]  D. Carroll,et al.  Low band gap donor-acceptor conjugated polymer nanoparticles and their NIR-mediated thermal ablation of cancer cells. , 2013, Macromolecular bioscience.

[4]  Zhouyi Guo,et al.  Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. , 2011, Biomaterials.

[5]  Xiaohua Huang,et al.  Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. , 2006, Journal of the American Chemical Society.

[6]  Zhuang Liu,et al.  PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy , 2013 .

[7]  Véronique Préat,et al.  To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Andrew Burgess,et al.  Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance , 2010, Proceedings of the National Academy of Sciences.

[9]  J. Irvin,et al.  Synthesis and Electropolymerization of 3,5-Bis-(3,4-ethylenedioxythien-2-yl)-4,4-dimethyl Isopyrazole: A Donor-Acceptor-Donor Monomer , 2013 .

[10]  Jay V. Shah,et al.  Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy , 2015, Journal of Nanoparticle Research.

[11]  Glenn P. Goodrich,et al.  Photothermal Efficiencies of Nanoshells and Nanorods for Clinical Therapeutic Applications , 2009 .

[12]  D. Xing,et al.  Synthesis and characterization of an HSP27-targeted nanoprobe for in vivo photoacoustic imaging of early nerve injury. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[13]  Kai Yang,et al.  In Vitro and In Vivo Near‐Infrared Photothermal Therapy of Cancer Using Polypyrrole Organic Nanoparticles , 2012, Advanced materials.

[14]  J. Yih,et al.  Facile Synthesis of Aqueous-dispersible Nano-PEDOT:PSS-co-MA Core/Shell Colloids Through Spray Emulsion Polymerization , 2011 .

[15]  Yi Liu,et al.  Photothermal ablation of bone metastasis of breast cancer using PEGylated multi-walled carbon nanotubes , 2015, Scientific Reports.

[16]  J L West,et al.  A whole blood immunoassay using gold nanoshells. , 2003, Analytical chemistry.

[17]  M. Hoepfner,et al.  Microscale Heat Transfer Transduced by Surface Plasmon Resonant Gold Nanoparticles. , 2007, The journal of physical chemistry. C, Nanomaterials and interfaces.

[18]  S. Ikeda,et al.  Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma. , 2015, Cancer treatment reviews.

[19]  A. Castro,et al.  Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events , 2014, Cell cycle.

[20]  James W Tunnell,et al.  Nanoparticle‐mediated photothermal therapy: A comparative study of heating for different particle types , 2012, Lasers in surgery and medicine.

[21]  P. Wust,et al.  Hyperthermia in combined treatment of cancer. , 2002, The Lancet Oncology.

[22]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Travis Cantu,et al.  Electroactive Polymer Nanoparticles Exhibiting Photothermal Properties. , 2016, Journal of visualized experiments : JoVE.

[24]  A. L. Dyer,et al.  Navigating the Color Palette of Solution-Processable Electrochromic Polymers† , 2011 .

[25]  A. Hayes Principles and methods of toxicology , 1982 .

[26]  K. Hunter,et al.  Targeting metastatic breast cancer: problems and potential. , 2015, F1000 faculty reviews.

[27]  B. Martin,et al.  Donor–acceptor–donor polymers utilizing pyrimidine-based acceptors , 2014 .

[28]  Ji-Xin Cheng,et al.  Gold nanorod-mediated photothermolysis induces apoptosis of macrophages via damage of mitochondria. , 2009, Nanomedicine.

[29]  Janusz Skowronek,et al.  Hyperthermia – description of a method and a review of clinical applications , 2007 .

[30]  C. Yeh,et al.  Comparative efficiencies of photothermal destruction of malignant cells using antibody-coated silica@Au nanoshells, hollow Au/Ag nanospheres and Au nanorods , 2009, Nanotechnology.

[31]  Prashant K. Jain,et al.  Plasmonic photothermal therapy (PPTT) using gold nanoparticles , 2008, Lasers in Medical Science.

[32]  B. Pelaz,et al.  Hyperthermia Using Inorganic Nanoparticles , 2012 .

[33]  H. Choi,et al.  In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. , 2009, ACS Nano.

[34]  Kai Yang,et al.  Organic stealth nanoparticles for highly effective in vivo near-infrared photothermal therapy of cancer. , 2012, ACS nano.

[35]  R. H. Donkol,et al.  Hyperthermia Tissue Ablation in Radiology , 2013 .