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

초록/요약

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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