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超声触发血卟啉单甲醚载脂质体治疗乳腺肿瘤的声动力学疗法。

Ultrasound-triggered breast tumor sonodynamic therapy through hematoporphyrin monomethyl ether-loaded liposome.

机构信息

Department of Pharmacy, Danyang People's Hospital, Danyang, China.

Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, China.

出版信息

J Biomed Mater Res B Appl Biomater. 2020 Apr;108(3):948-957. doi: 10.1002/jbm.b.34447. Epub 2019 Aug 6.

Abstract

Sonodynamic therapy (SDT) which employs ultrasound-triggered sonosensitizers to generate reactive oxygen species (ROS) has been proved to be effective for treatment of cancers. However, it is still desirable for sonosensitizers to be delivered to tumors as effectively as possible. In this study, we prepared the hematoporphyrin monomethyl ether (HMME)-loaded liposome as the sonosensitizers for SDT and evaluated their effects on human MCF-7 breast cancer cells in vitro and in vivo. Liposomes prepared by thin film hydration technique were about 100 nm in size with positive zeta potential and exhibited spherical in shape. Following irradiation of ultrasound which generates intracellular ROS, the liposome facilitated the delivery of HMME to tumor cells. HMME-loaded liposomes showed low cytotoxicity under basal condition but significant sonodynamic effects under ultrasonic irradiation. Notably, HMME-loaded liposomes exhibited spatial distribution of HMME in tumor tissues of mice. The promoted delivery of HMME into the tumors by liposomes was shown by the greater tumor growth inhibition than free HMME after 20-day treatment. Taken together, these results show that HMME-loaded liposome functions as a promising sonosensitizer for SDT, implying the efficient antitumor effects of HMME-based SDT on breast tumor.

摘要

声动力学疗法(SDT)利用超声触发声敏剂产生活性氧(ROS)已被证明可有效治疗癌症。然而,仍期望声敏剂尽可能有效地递送至肿瘤。在这项研究中,我们制备了载血卟啉单甲醚(HMME)的脂质体作为 SDT 的声敏剂,并在体外和体内评估了它们对人 MCF-7 乳腺癌细胞的作用。薄膜水化技术制备的脂质体大小约为 100nm,带有正 ζ 电位,呈球形。在超声产生细胞内 ROS 的照射后,脂质体促进了 HMME 向肿瘤细胞的传递。HMME 负载的脂质体在基础条件下表现出低细胞毒性,但在超声照射下具有显著的声动力学效应。值得注意的是,HMME 负载的脂质体在小鼠肿瘤组织中显示出 HMME 的空间分布。脂质体将 HMME 递送至肿瘤的促进作用表现为在 20 天治疗后,与游离 HMME 相比,肿瘤生长抑制作用更大。综上所述,这些结果表明 HMME 负载的脂质体可作为 SDT 的一种有前途的声敏剂,提示基于 HMME 的 SDT 对乳腺肿瘤具有有效的抗肿瘤作用。

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