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用于姜黄素介导的声动力疗法和钙超载的结肠癌外泌体衍生仿生纳米平台

Colon cancer exosome-derived biomimetic nanoplatform for curcumin-mediated sonodynamic therapy and calcium overload.

作者信息

Li Yang, Huang Chunyu, Xu Youhua

机构信息

Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.

School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.

出版信息

Front Bioeng Biotechnol. 2022 Nov 15;10:1069676. doi: 10.3389/fbioe.2022.1069676. eCollection 2022.

Abstract

Sonodynamic therapy (SDT) possesses unique properties such as being minimally invasive, exhibiting low toxicity, as well as ability to impart the treatment in the deep tissues, and hence has been extensively used. However, inherent defects such as low water-soluble sonosensitizers can limit the clinical application of SDT, and tumor microenvironment (TME) can further compromise the effect of a single SDT. To overcome these challenges, we have designed a bionic nano-system (ECaC) by coating mesoporous calcium carbonate nanoparticles (CaCO NPs) and sonosensitizer curcumin (Cur) into tumor-derived exosomes for developing enhanced SDT. Exosome membrane could endow CaCO NPs with homologous targeting abilities. In addition, compared with the bare CaCO3 NPs, ECaC showed significant accumulation in the tumor cell species. Subsequently, CaCO NPs upon reaching the tumor site can be degraded into Ca in response to the acidic microenvironment of the tumor to destroy the cellular mitochondria. Hence, the cellular respiration could be destroyed to be a vulnerable state, causing oxidative stress, enhancing Cur-mediated chemotherapy/SDT. This synergistically dynamic therapy has demonstrated significant anti-tumor effects under and settings without exhibiting any toxic side effects. Our prepared biomimetic nano-system can effectively deliver the hydrophobic Cur to the tumor sites, which holds great promise in field of drug delivery and can broaden the application of exosomes, as this method has a certain enlightenment effect on the subsequent development of exosomes.

摘要

声动力疗法(SDT)具有微创、低毒以及能够对深部组织进行治疗等独特特性,因此已被广泛应用。然而,诸如水溶性低的声敏剂等固有缺陷会限制声动力疗法的临床应用,并且肿瘤微环境(TME)会进一步削弱单次声动力疗法的效果。为了克服这些挑战,我们通过将介孔碳酸钙纳米颗粒(CaCO NPs)和声敏剂姜黄素(Cur)包裹在肿瘤来源的外泌体中,设计了一种仿生纳米系统(ECaC),以开发增强型声动力疗法。外泌体膜可赋予CaCO NPs同源靶向能力。此外,与裸露的CaCO3 NPs相比,ECaC在肿瘤细胞种类中显示出显著的积累。随后,到达肿瘤部位的CaCO NPs可响应肿瘤的酸性微环境降解为Ca,从而破坏细胞线粒体。因此,细胞呼吸可能被破坏至脆弱状态,引发氧化应激,增强Cur介导的化疗/声动力疗法。这种协同动态疗法在[具体条件1]和[具体条件2]设置下已显示出显著的抗肿瘤效果,且未表现出任何毒副作用。我们制备的仿生纳米系统能够有效地将疏水性Cur递送至肿瘤部位,在药物递送领域具有巨大潜力,并且可以拓宽外泌体的应用范围,因为该方法对后续外泌体的开发具有一定的启示作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/9705788/c4eb0e119a65/FBIOE_fbioe-2022-1069676_wc_sch1.jpg

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