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External Stimuli-Responsive Melanin-Like Nanoparticles for Photoacoustic Imaging-Guided Therapy
Lee, Sunho,Lee, Hohyeon,Han, Hyounkoo,Yoo, Hongkeun,Kim, Haemin,Chang, Jin Ho,Kim, Hyuncheol American Scientific Publishers 2018 Science Of Advanced Materials Vol.10 No.5
<P>Photoacoustic (PA) imaging potential for biomedical applications, such as image-guide therapy, has been accelerated by exogenous contrast agent development, because of its real-time functional imaging and non-ionizing. The goal of this study was to develop melanin-like nanoparticles (MeINPs) for amplified PA imaging and pH stimuli-responsive local drug delivery. MeINPs were produced with dopamine hydrochloride and included catechol and quinone functional groups on the surface. pH sensitive MeINPs (pH-MeINPs) were synthesized by reversibly blocking free primary amines. pH-MeINPs are stable in pH > 7; however, in slightly acidic conditions (pH 5.6), pH-MeINPs are aggregated, resulting in the amplification of PA signals. Additionally, the chemotherapeutic agent, doxorubicin (DOX), was bound onto the surface of pH-MeINPs by pi-pi and hydrogen bonding. Finally, pH-MeINPs conjugated onto the surface of a 1-2-mu m sized microbubble (MB) for an externally ultrasound-controlled release of pH-MeINPs around a local tumor site. In addition, the efficient delivery and penetration of released pH-MeINPs into tumor cells can be expected because of the sonoporation of microbubbles. Results showed that under the exposure of ultrasound, DOX-pH-MeINPs were released from the microbubbles and delivered into cells more efficiently, compared to the ultrasound non-exposed control group, because of the sonoporation. The pH-MeINPs released the loaded DOX more effectively in acidic than neutral conditions. Therefore, MB-DOX-pH-MeINPs could be applied to tumor-specific PA amplification strategies; DOX-pH-MeINPs nanoparticles could be released around a tumor site with focused ultrasound, and then control DOX release locally in tumors in response to stimuli such as low pH and reactive oxygen species.</P>
Combination of chemotherapy and photodynamic therapy for cancer treatment with sonoporation effects
Lee, Hohyeon,Han, Jieun,Shin, Heejun,Han, Hyounkoo,Na, Kun,Kim, Hyuncheol Elsevier 2018 Journal of controlled release Vol.283 No.-
<P><B>Abstract</B></P> <P>To overcome the limitations of single therapy, chemotherapy has been studied to be combined with photodynamic therapy. However, nanomedicine combining anticancer drug and photosensitizer still cannot address the insufficiency of drug delivery and the off-targeting effect. To address drug delivery issue, we have developed a doxorubicin encapsulating human serum albumin nanoparticles/chlorin e6 encapsulating microbubbles (DOX-NPs/Ce6-MBs) complex system. Microbubbles enable ultrasound-triggered local delivery via sonoporation for maximizing the drug delivery to a target site. In both <I>in vitro</I> and <I>in vivo</I> experiments, the developed DOX-NPs/Ce6-MBs drug delivery complex could be confirmed to transfer drugs deeply and effectively into cancerous tumors through the following three steps; (1) the local release of nanoparticles due to the cavitation of DOX-NPs/Ce6-MBs; (2) the enhanced extravasation of DOX-NPs and Ce6-liposome/micelle due to the sonoporation phenomenon; (3) the improved penetration of extravasated nanomedicines into the deep tumor region due to the mechanical energy of ultrasound. As a result, the developed DOX-NPs/Ce6-MBs complex with ultrasound irradiation showed increased therapeutic effects compared to the case where no ultrasound irradiation was applied. The DOX-NPs/Ce6-MBs was concluded from this study to be the optimal drug delivery system for external-stimuli local combination (chemotherapy + PDT) therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Nanoparticle/Microbubble complex can be an excellent carrier for multiple drugs. </LI> <LI> Microbubble in the complex can be used for both drug carrier and sonoporation. </LI> <LI> Sonoporation effects can improve local delivery efficiency of multiple drugs. </LI> <LI> Combination therapy can be improved by increasing tissue penetration of drugs. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>