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External stimuli-responsive melanin-like nanoparticles for photoacoustic imaging-guided therapy

이선호 (서강대학교 일반대학원)

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The great potential of photoacoustic imaging (PA) in biomedical imaging has been further accelerated by the development of exogenous contrast agents. PA imaging has great opportunities for image-guided therapy because of real-time and functional imaging and non-ionizing nature, compared to other ima...
The great potential of photoacoustic imaging (PA) in biomedical imaging has been further accelerated by the development of exogenous contrast agents. PA imaging has great opportunities for image-guided therapy because of real-time and functional imaging and non-ionizing nature, compared to other imaging techniques. The goal of this study was to develop melanin-like nanoparticles (MelNPs) for amplified PA imaging and stimuli-responsive local drug delivery. MelNPs were produced with dopamine hydrochloride and included surface catechol and quinone groups. Surface-modified MelNPs (pH-MelNPs) were synthesized by reversibly blocking free primary amines. pH-MelNPs are stable in pH > 7; however, in slightly acidic conditions (pH 5.6), the PA signal was amplified by a pH-MelNPs aggregation. Additionally, the chemotherapeutic agent doxorubicin (DOX) was bound to the surface of pH-MelNPs by π-π and hydrogen bonding. Finally, pH-MelNPs conjugated on 1–2-µm microbubble (MB) surfaces cavitated by ultrasound (US). When target sites were irradiated with US waves, MB surface-conjugated DOX-pH-MelNPs penetrated cell membranes. Results showed that sonoporation dramatically increased MB-DOX-pH-MelNPs cell uptake, and loaded DOX was more effectively released in acidic than neutral conditions. Therefore, MB-DOX-pH-MelNPs could be applied to tumor-specific PA amplification strategies; they could control DOX release locally in tumors in response to stimuli such as low pH and reactive oxygen species; and sonoporation in tumors could occur with locally targeted US waves
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