超声介导的微泡脂质体给药阿霉素增强抗肿瘤疗效和降低心脏毒性。

IF 2.4 3区 医学 Q2 ACOUSTICS
Mingyu He, Xucai Chen, Francois Yu, Bin Qin, Huizhu Wang, Linda Lavery, Flordeliza S Villanueva
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引用次数: 0

摘要

目的:阿霉素(Dox)是治疗肉瘤的标准护理,但累积剂量往往受到心脏毒性的限制。我们假设超声靶向脂质体多柔比星(LDox)共轭聚合物微泡复合物(DoxLPX)的微泡(MB)空化(UTMC)可以增强肿瘤抑制作用并限制Dox的心脏毒性。方法:在MCA205肉瘤小鼠体内静脉注射DoxLPX,并发超声至肿瘤部位(DoxLPX + UTMC)。其他小鼠接受等量的游离Dox、LDox或LDox + MB与UTMC (LDox + MB + UTMC)联合给药。连续超声检查肿瘤大小和心功能。对死后心脏组织进行细胞凋亡分析。Dox的生物分布通过死后生物发光成像进行,其中Cy5.5用作荧光Dox类似物。结果:DoxLPX + UTMC在肿瘤中药物浓度升高,肿瘤生长明显减缓,中位生存时间延长。LDox和DoxLPX制剂可减少药物外渗进入心肌。与游离Dox和LDox相比,LDox + MB + UTMC也表现出更好的肿瘤生长抑制作用。治疗开始后3周,DoxLPX + UTMC组左心室功能指标明显优于游离Dox组,与生物分布结果一致。同时,DoxLPX + UTMC组心肌细胞结构正常,间质/血管周围纤维化明显减少。结论:与全身游离Dox相比,DoxLPX联合超声给药提供了一个靶向给药平台,具有更好的抗肿瘤疗效和降低心脏毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhanced Antitumor Efficacy and Reduced Cardiotoxicity of Ultrasound-Mediated Doxorubicin Delivery by Microbubble-Liposome Complexes.

Objective: Doxorubicin (Dox) is standard of care for treatment of sarcomas, but cumulative dosing is often limited by cardiotoxicity. We hypothesized that ultrasound targeted microbubble (MB) cavitation (UTMC) of a liposomal doxorubicin (LDox) conjugated polymer microbubble complex (DoxLPX) would enhance tumor inhibition and limit Dox cardiotoxicity.

Methods: DoxLPX was intravenously injected in MCA205 sarcoma-bearing mice and concurrent ultrasound was delivered to the tumor site (DoxLPX + UTMC). Other mice received equivalent dosages of free Dox, LDox, or LDox + MB co-administration with UTMC (LDox + MB + UTMC). Tumor size and cardiac function were serially imaged with ultrasound. Postmortem cardiac tissue was analyzed for apoptosis. Biodistribution of Dox was performed with bioluminescence imaging postmortem where Cy5.5 was used as a fluorescent Dox analog.

Results: DoxLPX + UTMC showed increased drug concentration in the tumor, a significant slowdown in tumor growth and prolonged median survival time. LDox and DoxLPX formulations had reduced drug extravasation into the myocardium. LDox + MB + UTMC also demonstrated superior tumor growth inhibition compared to free Dox and LDox. Three weeks after treatment commenced, DoxLPX + UTMC group showed significantly better left ventricular function indices than the free Dox group, consistent with biodistribution findings. Concordantly, heart tissue showed normal architecture of cardiac myocytes and significantly less interstitial/perivascular fibrosis in the DoxLPX + UTMC group.

Conclusions: DoxLPX formulation in conjunction with ultrasound provides a targeted drug delivery platform with superior anti-tumor efficacy and reduced cardiac toxicity compared with systemic administration of free Dox.

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来源期刊
CiteScore
6.20
自引率
6.90%
发文量
325
审稿时长
70 days
期刊介绍: Ultrasound in Medicine and Biology is the official journal of the World Federation for Ultrasound in Medicine and Biology. The journal publishes original contributions that demonstrate a novel application of an existing ultrasound technology in clinical diagnostic, interventional and therapeutic applications, new and improved clinical techniques, the physics, engineering and technology of ultrasound in medicine and biology, and the interactions between ultrasound and biological systems, including bioeffects. Papers that simply utilize standard diagnostic ultrasound as a measuring tool will be considered out of scope. Extended critical reviews of subjects of contemporary interest in the field are also published, in addition to occasional editorial articles, clinical and technical notes, book reviews, letters to the editor and a calendar of forthcoming meetings. It is the aim of the journal fully to meet the information and publication requirements of the clinicians, scientists, engineers and other professionals who constitute the biomedical ultrasonic community.
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