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超声辅助将叶酸基碳量子点包封在乳腺癌细胞衍生的外泌体中,作为共受体介导的抗癌纳米载体,用于增强乳腺癌治疗。

Ultrasound-assisted encapsulating folic acid-based carbon quantum dots within breast cancer cell-derived exosomes as a co-receptors-mediated anticancer nanocarrier for enhanced breast cancer therapy.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Sci Rep. 2024 Jul 23;14(1):16941. doi: 10.1038/s41598-024-67934-6.

Abstract

The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer.

摘要

癌症药物递送的非特异性通常会导致乳腺癌治疗过程中产生大量毒性副作用。为了减轻这些负面后果,我们的方法涉及将甲氨蝶呤(MTX)装载到由叶酸合成的碳量子点(CQDs)中,然后将其包裹在源自乳腺癌细胞的外体膜中(Ex@MTX-CQDs)。利用纳米颗粒跟踪技术的分析表明,这些 Ex@MTX-CQDs 保持了其外体前体的物理和生化特性。MTX 的释放曲线表明,在正常生理条件下,其释放百分比受到限制(低于 10%),而在模拟肿瘤组织中发现的条件时,其释放率更为一致(约 65%)。毒理学评估已证实,外体与剩余叶酸的存在通过与叶酸和硫酸乙酰肝素蛋白聚糖受体结合,可显著提高 MTX 直接递送到癌细胞中的递送效果。这一过程导致线粒体膜电位的破坏增加,随后触发细胞凋亡,最终导致癌细胞的破坏。我们的研究可能为基于生物来源的纳米载体在乳腺癌的靶向治疗中的进一步创新和应用做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/11266556/7b7a189ccb61/41598_2024_67934_Fig1_HTML.jpg

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