Assessing fluorescence detection and effective photothermal therapy of near-infrared polymer nanoparticles using alginate tissue phantoms.

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Photothermal therapy (PTT) uses light absorbing materials to generate heat for treatment of diseases, like cancer. The advantages of using PTT components that absorb in the near-infrared (NIR) include reduced tissue auto-fluorescence and higher penetration depths. However, NIR laser light can still be scattered and absorbed by biological tissues, thus decreasing the amount of the energy reaching the PTT agents. We have developed two distinct formulations of NIR-absorbing nanoparticles, one which can be utilized for PTT only, and another for both PTT and fluorescence imaging of colorectal cancer. In this work, the fluorescence detection limit and the PTT heating potential of the two nanoparticle types were determined using alginate tissue phantoms. The objective of this study was to determine the PTT efficiency and theranostic potential of the nanoparticles by irradiating 3D collagen tumor spheroids, containing nanoparticles and CT26 mouse colorectal cancer cells, through increasing tissue phantom thicknesses and then quantifying cell death. Materials and Methods Our lab has previously developed nanoparticles based on the semiconducting, conjugated polymer 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). We have also made a hybrid nanoparticle that heats and fluoresces by combining PCPDTBSe polymer with the fluorescent poly[(9,9-dihexylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBTDBT10) polymer to yield nanoparticles termed Hybrid Donor-Acceptor Polymer Particles (H-DAPPs). H-DAPPs and PCPDTBSe nanoparticles were added to three-dimensional collagen gel tumor spheroids in order to represent nanoparticles in a tumor. Alginate tissue phantoms, comprised of an optical scattering agent (Intralipid) and an optical absorbing material (hemoglobin) in order to mirror biological tissue scattering effects, were used to simulate increasing tissue thickness between the nanoparticles and the PTT energy source. Fluorescence from the H-DAPPs was detectable through 6 mm of tissue phantoms. It was found that less than 10% of the laser energy could penetrate through 9 mm of tissue phantoms and only 60% of the laser energy passed through the 1.5 mm phantoms, regardless of laser power. PTT experiments, using 800 nm light at 2.2 W/cm2 for 60 s through tissue phantoms to stimulate nanoparticle-doped tumor spheroids, showed 55% cell death through 3 mm of tissue phantoms using H-DAPPs. Results from using the PCPDTBSe nanoparticles showed 72% cell death through 3 mm and over 50% cell death through 6 mm of tissue phantoms. The results of this work validated the heating potential and fluorescence detection limitations of two theranostic polymer nanoparticles by utilizing alginate tissue phantoms and 3D tumor spheroids. H-DAPPs and PCPDTBSe polymer nanoparticles can be utilized as effective PTT agents by exploiting their absorption of NIR light and H-DAPPs have advantageous fluorescence for imaging colorectal cancer. The data generated from this study design can allow for other NIR absorbing and fluorescing nanoparticle formulations to be evaluated prior to in vivo experimentation. Lasers Surg. Med. 50:1040-1049, 2018. © 2018 Wiley Periodicals, Inc.