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Han, Hyounkoo,Lee, Hohyeon,Kim, Kwangmeyung,Kim, Hyuncheol Elsevier Science Publishers 2017 Journal of controlled release Vol.266 No.-
<P><B>Abstract</B></P> <P>Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy.</P> <P><B>Graphical abstract</B></P> <P>The therapeutic strategy using HIFU in conjunction with a nanomedicines-microbubble complex allows the locally preferential accumulation of nanomedicines in the tumor and enhanced penetration of nanomedicines into deeper tumor region.</P> <P>[DISPLAY OMISSION]</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>