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高效金纳米粒子-抗体介导的药物递送至肺癌干细胞的光动力治疗。

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells.

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.

出版信息

Int J Mol Sci. 2020 May 26;21(11):3742. doi: 10.3390/ijms21113742.

DOI:10.3390/ijms21113742
PMID:32466428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7311980/
Abstract

Cancer stem cells (CSCs) are a leading contributor to lung cancer mortality rates. CSCs are responsible for tumor growth and recurrence through inhibition of drug-induced cell death, decreasing the effect of traditional cancer therapy and photodynamic therapy (PDT). PDT can be improved to successfully treat lung cancer by using gold nanoparticles (AuNPs), due to their size and shape, which have been shown to facilitate drug delivery and retention, along with the targeted antibody (Ab) mediated selection of CSCs. In this study, a nanobioconjugate (NBC) was constructed, using a photosensitizer (PS) (AlPcSCl), AuNPs and Abs. The NBC was characterized, using spectroscopy techniques. Photodynamic effects of the NBC on lung CSCs was evaluated, using biochemical assays 24 h post-irradiation, in order to establish its anticancer effect. Results showed successful conjugation of the nanocomposite. Localization of the NBC was seen to be in integral organelles involved in cell homeostasis. Biochemical responses of lung CSCs treated using AlPcSCl -AuNP and AlPcSCl-AuNP-Ab showed significant cell toxicity and cell death, compared to free AlPcSCl. The PDT effects were enhanced when using the NBC, showing significant lung CSC destruction to the point of eradication.

摘要

癌症干细胞(CSC)是导致肺癌死亡率居高不下的主要原因之一。CSC 通过抑制药物诱导的细胞死亡来促进肿瘤生长和复发,从而降低传统癌症治疗和光动力疗法(PDT)的效果。通过使用金纳米粒子(AuNPs)可以改善 PDT,成功治疗肺癌,这是因为其大小和形状有利于药物输送和保留,同时还可以通过靶向抗体(Ab)介导的 CSC 选择。在这项研究中,构建了一种纳米生物缀合物(NBC),使用光敏剂(PS)(AlPcSCl)、AuNPs 和 Abs。使用光谱技术对 NBC 进行了表征。通过生化分析在辐照后 24 小时评估 NBC 对肺 CSC 的光动力作用,以确定其抗癌作用。结果表明成功地进行了纳米复合材料的共轭。NBC 的定位被观察到在涉及细胞内稳态的完整细胞器中。与游离 AlPcSCl 相比,用 AlPcSCl-AuNP 和 AlPcSCl-AuNP-Ab 处理的肺 CSC 的生化反应显示出明显的细胞毒性和细胞死亡。当使用 NBC 时,PDT 效果得到增强,显示出显著的肺 CSC 破坏,甚至达到根除的程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/48430cbf4323/ijms-21-03742-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/70968f02bac8/ijms-21-03742-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/8bf0df81af1c/ijms-21-03742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/bf682728845b/ijms-21-03742-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/d5ec77b53d3a/ijms-21-03742-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/48430cbf4323/ijms-21-03742-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/fdbb07b4f9d8/ijms-21-03742-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/75ace2ea2f39/ijms-21-03742-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/8dd93e7ecbfc/ijms-21-03742-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/4cf9a3220f75/ijms-21-03742-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/70968f02bac8/ijms-21-03742-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/8bf0df81af1c/ijms-21-03742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/bf682728845b/ijms-21-03742-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/d5ec77b53d3a/ijms-21-03742-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f7/7311980/48430cbf4323/ijms-21-03742-g009.jpg

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