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.
Visualizing biological markers and delivering bioactive agents to living organisms are important to biological research. In recent decades, photoacoustic imaging (PAI) has been significantly improved in the area of molecular imaging, which provides high-resolution volume imaging with high optical absorption contrast. To demonstrate the ability of nanoprobes to target tumors using PAI, we synthesize convertible nanostructured agents with strong photothermal and photoacoustic properties and linked the nanoprobe with biotin to target tumors in small animal model. Interestingly, these nanoprobes allow partial to disassemble in the presence of targeted proteins that switchable photoactivity, thus the nanoprobes provides a fluorescent-cancer imaging with high signal-to-background ratios. The proposed nanoprobe produce a much stronger PA signal compared to the same concentration of methylene blue (MB), which is widely used in clinical study and contrast agent for PAI. The biotin conjugated nanoprobe has high selectivity for biotin receptor positive cancer cells such as A549 (human lung cancer). Then we subsequently examined the PA properties of the nanoprobe that are inherently suitable for in vivo PAI. After injecting of the nanoprobe via intravenous method, we observed the mice’s whole body by PA imaging and acquired the PA signal near the cancer. The PA signal increased linearly with time after injection and the fluorescence signal near the cancer was confirmed by fluorescence imaging. The ability to target a specific cancer of the nanoprobe was well verified by PA imaging. This study provides valuable perspective on the advancement of clinical translations and in the design of tumor-targeting phototheranostic agents that could act as new nanomedicines.
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