Photothermal therapy (PTT) is a type of noninvasive, topical cancer treatment technique with photosensitive reagent that thermally reacts to a local laser irradiation over malignant tumor site. While phthalocyanine (Pc) variates are promising photosensitizer candidate having an excellent optical property tuned to deep penetrating near-infrared (NIR)-I window and generates high yield of reactive oxygen series, the hydrophobic characteristic of Pc does not withstand to general intravenous administration, which greatly limits the dye to penetrate into tumor tissue and ultimately lowers the treatment efficacy. The noncovalent conjugation with electron-rich transferrin (TF) not only increase the solubility of the dye, and but also quench the fluorescence and incapacitate strong photoinduced electron transfer required for reactive oxygen generation, which feeds back the dye to transform into interconvertible photothermal theragnostic contrast agent both for photoacoustic (PA) imaging and PTT. Moreover, the TF receptor-rich tumor cells are actively targetable and mediate high accumulation to the tumor site. The in vitro experiment demonstrated the feasible PA absorption spectra of ZnPcN4-TF, and extended aggregation test revealed the homogeneous superiority of ZnPcN4-TF compared to ZnPcN4 lumps. Lastly, the 72-hour in vivo whole-body photoacoustic imaging of MCF-7 tumor bearing mice was sequentially taken under two nominal wavelengths (710 nm as peak PA signal level, 800 nm as noise-equivalent level). From the result, the increased liver uptake verified the enhanced solubility, and active targetability toward MCF-7 tumor cell appeared in 54% PA signal level increase at maximum in after 8-hour postinjection.
Photoacoustic imaging has begun to be widely used to observe drug delivery and accumulation in the body. Theranostic, which includes both diagnosis and therapy, is an attractive approach for treating cancer. In this study, we synthesized nanomaterials and verified the theranostic effect through fluorescence and photoacoustic imaging. Selectively transporting a drug to the tumor site is essential to increase the therapeutic effect while reducing side effects. BODIPY has the advantages of being able to change its structure more easily, good photostability, good biocompatibility and high absorption coefficient than cyanine or porphyrin dyes, however they are limited to in vivo experiment due to their poor water solubility. We overcome the limitations of BODIPY-based materials by encapsulating in micellar nanoparticles with Hexa BODIPY cyclophosphazene (HBCP) and DSPE-PEG2000 polymer. HBCP NPs also have a property of selectively accumulating in tumors with enhanced permeability and retention effect due to their bulky nano-size molecular structure. We checked the tumor targeting and retention time of HBCP NPs by monitoring them with fluorescence imaging. In addition, the high heat conversion efficiency of HBCP NPs enables photoacoustic imaging and Photothermal therapy. We also conducted whole body scanning of tail-vein injected tumor-bearing mice with acoustic resolution photoacoustic microscopy system to provide tumor accumulation information of HBCP NP with vascular structure. The result suggests that HBCP NP has a potential to be used as a material for image guided phototherapy.
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