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设计并组装一种纳米颗粒、抗体、酞菁支架,用于将光敏剂递送至人乳头瘤病毒转化的癌细胞内。

Design and assembly of a nanoparticle, antibody, phthalocyanine scaffold for intracellular delivery of photosensitizer to human papillomavirus-transformed cancer cells.

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa.

出版信息

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):205-216. doi: 10.1080/21691401.2023.2199037.

Abstract

In photodynamic therapy (PDT), internalization and uptake of the photosensitizer (PS) by the cells is a passive process that relies on the enhanced permeability and retention (EPR) effect of tumour tissues due to their vasculature, increased LDL receptors, and decreased lymphatic drainage But as worries about PDT resistance grow, using passive techniques to administer PSs is becoming less and less viable. According to reported resistance mechanisms, it is necessary to improve PS delivery by changing PS absorption and bioavailability in order to enhance the therapeutic outcome. Therefore, in this study, a multifunctional photosensitizing agent with specific monoclonal antibodies (mAbs) to E6 oncoproteins was developed for PDT of human papillomavirus (HPV)-transformed cancer cells. Using PEGylated Gold Nanoparticles (PEGy-AuNP) at the core, anti-E6 mAbs and phthalocyanines were bound together. This compound demonstrated enhanced internalization of PS, resulting in enhanced PDT effects. In spite of being demonstrated , the substance in this work is intended for application, and conclusions are drawn to suggest possible outcomes for models based on observed data. By making PSs more bioavailable, facilitating their entry into cells, and preventing efflux through intracellular binding, this strategy may reduce cellular resistance to PDT.

摘要

在光动力疗法(PDT)中,光敏剂(PS)被细胞内化和摄取是一个被动过程,这依赖于肿瘤组织由于其血管、增加的 LDL 受体和减少的淋巴引流而具有的增强的通透性和保留(EPR)效应。但是,随着对 PDT 耐药性的担忧增加,使用被动技术来施用 PS 的可行性越来越低。根据报道的耐药机制,有必要通过改变 PS 的吸收和生物利用度来改善 PS 的递送,以增强治疗效果。因此,在这项研究中,开发了一种具有针对 E6 癌蛋白的特异性单克隆抗体(mAbs)的多功能光敏剂,用于治疗人乳头瘤病毒(HPV)转化的癌细胞的 PDT。使用聚乙二醇化金纳米粒子(PEGy-AuNP)作为核心,将抗 E6 mAbs 和酞菁结合在一起。该化合物表现出增强的 PS 内化,从而增强了 PDT 效果。尽管已经证明了,这项工作中的物质旨在应用,并根据观察到的数据得出结论,建议对模型进行可能的结果。通过使 PS 更具生物利用度,促进其进入细胞,并通过细胞内结合防止外排,可以降低细胞对 PDT 的耐药性。

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