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약물이 탑재된 미소기포와 결합된 sonoporation: 유방암세포에 대한 치료효과
박주현,이한아,이유경,서종범 한국음향학회 2022 韓國音響學會誌 Vol.41 No.5
공학적으로 제작된 미소기포 중 가스층과 유체층을 함께 내포하는 echogenic liposome은 수용성 약물 탑재에용이하다. 또한 특정 위치에서 약물을 방출할 수 있다는 점에서 초음파 조영제의 기능을 넘어서 초음파 기반 약물전달(sonoporation)에 활용될 수 있다. 이에 따라, 본 논문에서는 이전 연구에서 제안된 echogenic liposome의 구조를EF-TEM으로 재확인하였으며 sonoporation에서 약물전달 매개체로의 효과를 세포실험을 통하여 입증하였다. 세포실험은 유방암 조직인 MDA-MB-231 세포 대상으로 대표적 암치료제인 Doxorubicin을 지표 약물로 활용하였다. 비교군(1 그룹), Doxorubicin 그룹(2 그룹), Doxorubicin 과 일반 기포를 추가하여 sonoporation을 한 그룹(3 그룹), Doxorubicin을 echogenic liposome에 탑재하여 sonoporation을 적용한 그룹(4 그룹)으로 구분하여 진행한 실험결과, 4 그룹에서 약물 전달 효과가 초기부터 급격히 증가하였으며, 최종적으로 2 그룹과 3그룹에 비하여 최소 1.4 배 이상 효과적으로 종양 세포 괴사를 유도하였다. 따라서 sonoporation에서 echogenic liposome은 기존 일반적 미소기포보다 더 효율적인 약물 매개체라고 결론 내릴 수 있다.
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>
김도연,Park Suhyun,Yoo Hongkeun,Park Suhyeon,Kim Jeewon,Yum Kyuhee,김광명,Kim Hyuncheol 나노기술연구협의회 2020 Nano Convergence Vol.7 No.30
One of the major obstacles to successful chemotherapy is multi-drug resistance (MDR). A multi-drug resistant cancerous cell abnormally overexpresses membrane transporters that pump anticancer drugs out of the cell, resulting in low anticancer drug delivery efficiency. To overcome the limitation, many attempts have been performed to inhibit the abilities of efflux receptors chemically or genetically or to increase the delivery efficiency of anticancer drugs. However, the results have not yet been satisfactory. In this study, we developed nanoparticle-microbubble complexes (DOX-NPs/Ce6-MBs) by conjugating doxorubicin loaded human serum albumin nanoparticles (DOX-NPs) onto the surface of Chlorin e6 encapsulated microbubbles (Ce6-MBs) in order to maximize anticancer efficiency by overcoming MDR. Under the ultrasound irradiation, DOX-NPs and Ce6 encapsulating self-assembled liposomes or micelles were effectively delivered into the cells due to the sonoporation effect caused by the microbubble cavitation. At the same time, reactive oxygen (ROS) generated from intracellularly delivered Ce6 by laser irradiation arrested the activity of ABCG2 efflux receptor overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), resulting in increased the chemotherapy efficacy. In addition, the total number of side population cells that exhibit the properties of cancer stem-like cells were also reduced by the combination of photodynamic therapy and chemotherapy. In conclusion, DOX-NPs/Ce6-MBs will provide a platform for simultaneously overcoming MDR and increasing drug delivery and therefore, treatment efficiency, under ultrasound irradiation.
Development of HIFU-responsive complex for enhanced delivery of siRNA in cancer therapy
김도연,한현구,장용호,김광명,김현철 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-
To overcome the low therapeutic efficiency of single chemotherapy, nanotechnology-mediated combination therapies, especially combinations of siRNAs and chemotherapeutics such as paclitaxel (PTX), are promising alternatives for cancer therapy. However, some limitations, such as low delivery efficiency and therapeutic efficacy need to be overcome to achieve the enhanced efficacy. In addition, the co-delivery of siRNAs and chemotherapeutics with different physicochemical properties remains challenging. Here, high intensity focused ultrasound (HIFU)-responsive nanocomplexes, referred to as siRNA-NPPTX- MBs, were developed to address these limitations. These nanocomplexes were capable of co-delivering siRNA and PTX. We showed that these nanocomplexes could co-deliver drugs deep into the tumor, due to the ability to penetrate the dense extracellular matrix via the sonoporation under the exposure of HIFU, resulting in both enhanced RNA interference and chemotherapeutic effects.
Combining Ultrasound-Mediated Intracellular Delivery with Microfluidics in Various Applications
Huang Guangyong,Lin Lin,Wu Shixiong,Dang Haojie,Cheng Xuesong,Liu Ying,You Hui 한국바이오칩학회 2024 BioChip Journal Vol.18 No.1
Ultrasound-mediated intracellular delivery is one of the popular technologies based on membrane rupture at present. To date, ultrasound directly acts on a large number of cells to achieve cargo delivery and has been widely used in drug deliv-ery, disease therapy and other fields. However, the existing macroscopic methods can no longer meet the requirements of accurate tracking and analysis and are prone to extensive cell damage and even death. With the rapid advancements in microfl uidic technologies, the combination of ultrasound and microfluidics (CUM) technology can effectively improve the delivery efficiency and cell survival rates. This new technology has rapidly become a new direction and focus of research. Thus, we analysed the mechanism of sonoporation and the effect of acoustic waves in a microfluidic channel. In addition, we reviewed the application of these new technologies in terms of structure and fabrication of ultrasound transducers and microfl uidic devices. As regards our main objective, we hope to help researchers better understand the future developments and the challenges of new technologies. With this review, researchers can promote the development of new technologies to solve the current challenges of intracellular delivery and advance clinical applications.