유방암 동물모델에서의 저강도 집속초음파를 이용한 마이크로버블 및 마이크로버블-나노물질 복합체 기반 항암제 전달 효율 검증
Effects of Anticancer Drug Delivery based on Microbubble and Microbubble-Nanoparticle Complex using Low-Intensity Focused Ultrasound in Breast Cancer Animal Model
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Ultrasound sonication along with microbubble (MB) could enhance drug delivery to promote the absorption of anticancer drugs into cancers in a noninvasive and targeted manners. In this study, we verify the acute drug delivery enhancement (within an hour) of two representative focused ultrasound driven drug delivery enhancement methods (MB and Doxorubicin-coated Nanoparticle complex (MB-NP) based). Experiments were conducted using in vivo mouse model with MDA-MB-231 breast cancer cell line. Ultrasound generated by single-element 1 MHz focused ultrasound transducer was delivered in pulsed sonication consisted of 0.125 msec bursts at a pulse repetition frequency of 2 Hz for 20 seconds without a significant increase in local temperature (less than 0.1oC) or hemorrhage. Doxorubicin concentrations in tumors were improved by 1.97 times in the case of MB-NP, and 1.98 times by using Doxorubicin and MB separately. These results indicate anticancer drug delivery based on MB and MB-NP can sig-nificantly improve the effect of anticancer drugs delivered to tumors in a short time period by using low-intensity focused ultrasound.
Abstract
Ultrasound sonication along with microbubble (MB) could enhance drug delivery to promote the absorption of anticancer drugs into cancers in a noninvasive and targeted manners. In this study, we verify the acute drug delivery enhancement (within an hour) of two representative focused ultrasound driven drug delivery enhancement methods (MB and Doxorubicin-coated Nanoparticle complex (MB-NP) based). Experiments were conducted using in vivo mouse model with MDA-MB-231 breast cancer cell line. Ultrasound generated by single-element 1 MHz focused ultrasound transducer was delivered in pulsed sonication consisted of 0.125 msec bursts at a pulse repetition frequency of 2 Hz for 20 seconds without a significant increase in local temperature (less than 0.1oC) or hemorrhage. Doxorubicin concentrations in tumors were improved by 1.97 times in the case of MB-NP, and 1.98 times by using Doxorubicin and MB separately. These results indicate anticancer drug delivery based on MB and MB-NP can sig-nificantly improve the effect of anticancer drugs delivered to tumors in a short time period by using low-intensity focused ultrasound.
참고문헌 (26)
- D. L. Miller, "Overview of therapeutic ultrasound applications and safety considerations", Journal of Ultrasound in Medicine, 31(4), pp.623~634 (2012)
- G. R. Ter Haar, "High intensity focused ultrasound for the treatment of tumors", Echocardiography, 18(4), pp.317~322 (2001)
- J. Kennedy, "High intensity focused ultrasound : surgery of the future?", The British journal of radiology, 76(909), pp.590~599 (2003)
- F. Wu, "A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer", British journal of cancer, 89(12), pp.2227~2233 (2003)
- A. Blana, "High-intensity focused ultrasound for the treatment of localized prostate cancer : 5-year experience", Urology, 63(2), pp.297~300 (2004)
- X. -L. Ren, "Extracorporeal ablation of uterine fibroids with high?intensity focused ultrasound : imaging and histopathologic evaluation", Journal of ultrasound in medicine, 26(2), pp.201~212 (2007)
- J. E. Kennedy, "High-intensity focused ultrasound in the treatment of solid tumours", Nature reviews cancer, 5(4), pp.321~327 (2005)
- Y. -H. Hsiao, "Clinical application of high-intensity focused ultrasound in cancer therapy", Journal of cancer, 7(3), pp.225~231 (2016)
- H. Grüll, "Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRIguided high intensity focused ultrasound", Journal of Controlled Release, 161(2), pp.317~327 (2012)
- R. Illing, "The safety and feasibility of extracorporeal high-intensity focused ultrasound(HIFU)for the treatment of liver and kidney tumours in a Western population", British journal of cancer, 93(8), pp.890~895 (2005)
- K. Wang, "Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer", Oncology Research and Treatment, 36(3), pp.88~92 (2013)
- W. G. Pitt, "Ultrasonic drug delivery–a general review", Expert opinion on drug delivery, 1(1), pp.37~56 (2004)
- S. Hernot, "Microbubbles in ultrasoundtriggered drug and gene delivery", Advanced drug delivery reviews, 60(10), pp.1153~1166 (2008)
- J. Escoffre, "Doxorubicin delivery into tumor cells with ultrasound and microbubbles", Molecular pharmaceutics, 8(3), pp.799~806 (2011)
- M. Todorova, "Antitumor effects of combining metronomic chemotherapy with the antivascular action of ultrasound stimulated microbubbles", International journal of cancer, 132(12), pp.2956~2966 (2013)
- T. Li, "Pulsed high intensity focused ultrasound(pHIFU)enhances delivery of doxorubicin in a preclinical model of pancreatic cancer", Cancer research, 75(18), pp.3738~3746 (2015)
- N. Rapoport, "Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy", Journal of the National Cancer Institute, 99(14), pp.1095~1106 (2007)
- I. Lentacker, "Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery : cytotoxicity and mechanisms involved", Molecular Therapy, 18(1), pp.101~108 (2010)
- Y. Zhang, "Mechanical force-triggered drug delivery", Chemical reviews, 116(19), pp.12536~12563 (2016)
- Shin-Woo Ha, "Method for producing albumin particles coated with anticancer agent", KR 10-2018-0064430, applied on 06.04.2018, ~ (2018)
- S. Tinkov, "New doxorubicin-loaded phospholipid microbubbles for targeted tumor therapy : In-vivo characterization", Journal of Controlled Release, 148(3), pp.368~372 (2010)
- J. Park, "Evaluation of permeability, doxorubicin delivery, and drug retention in a rat brain tumor model after ultrasound-induced blood-tumor barrier disruption", Journal of Controlled Release, 250, pp.77~85 (2017)
- S. Cai, "Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer", Journal of Controlled Release, 146(2), pp.212~218 (2010)
- C. J. Teirlinck, "Development of an example flow test object and comparison of five of these test objects, constructed in various laboratories", Ultrasonics, 36(1-5), pp.653~660 (1998)
- N. M. Hijnen, "Tumour hyperthermia and ablation in rats using a clinical MR?HIFU system equipped with a dedicated small animal set-up", International journal of hyperthermia, 28(2), pp.141~155 (2012)
- C. Lan, "Quantitative histology analysis of the ovarian tumour microenvironment", Scientific reports, 5, pp.16317~ (2015)