Hybrid Donor-Acceptor Polymer Particles for Fluorescent Identification and Photothermal Treatment of Cancer
Nicole Levi, Elizabeth Gurysh, Eleanor McCabe-Lankford, Chris MacNeill, and Santu Sarkar
Department of Plastic and Reconstructive Surgery, Wake Forest School of Medicine, Winston-Salem, NC USA
nlevi@wakehealth.edu
Abstract
Donor acceptor polymer particles (DAPPs) are routinely designed to altering their optical absorption properties for detection and treatment of breast or colorectal cancer. DAPPs were composed of poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), which generates heat upon NIR stimulation. This was combined with poly[(9,9-dihexylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBTDBT10), which is a fluorescent polymer that allows for in vivo detection of the nanoparticles. Cytotoxicity assays were then done to evaluate the effect of the DAPPs on breast or colorectal cancer cells, with and without infrared stimulation. Photothermal ablation assays in 2D or 3D were performed to determine the concentrations of nanoparticles needed to induce cell death. Then mammary fat pad tumors were induced in Balb/c mice using the bioluminescent 4T1 murine breast cell line. DAPPs were delivered systemically without a tumor specific ligand, and then the animals were imaged to examine the overlap of the fluorescence of the nanoparticles with the bioluminescent cancer cells. Photothermal ablation was then performed by exposing the tumors to 3-5 W /cm2 of 800 nm light. Alternatively CT26 murine colorectal cancer cells were used to develop micro-metastasis in the abdomen of Balb/C mice. Peritoneal delivery identified that DAPPs localized to tumors to identify where NIR stimulation needed to be applied in an open abdomen. NIR stimulation led to selective photothermal ablation of the breast tumors, leading to prolonged animal survival. A significant advantage is that polymer nanoparticles can localize to breast tumors without the need of a tumor-guiding molecule. Photothermal ablation was not possible for widespread treatment of disseminated colorectal cancer, due to the optical absorption of the abdominal vasculature. However, the nanoparticles may be useful for fluorescently detecting tumors for resection during surgical procedures. Donor acceptor polymer nanoparticles are stable, inert, not subject to oxidation, and can be heated and imaged repeatedly without loss of their fluorescence or heat generating capacity.
Short Bio
Nicole Levi, Ph.D., is an Associate Professor and Director of Materials Research Innovation and Development in the Department of Plastic and Reconstructive Surgery. She has training in Physics and Biomedical Engineering, with specific expertise in the field of nanotechnology. The primary focus of her research is on the development of heat-generating materials. One facet of her research involves the synthesis of nanoparticles composed of donor-acceptor conjugated polymers that can both fluoresce, and be optically-stimulated to generate heat. She is the PI of a DOD-supported study to evaluate these nanoparticles in cancer models for detection, ablation and chemo-sensitization of breast and colorectal cancer. Dr. Levi-Polyachenko’s strength is the development of innovative materials to solve medical problems, and she has eleven patents on her work to date.