纳米颗粒、抗体和酞菁蓝的设计和组装支架,用于将光敏剂递送到人乳头瘤病毒转化的癌细胞内部。
Design and assembly of a nanoparticle, antibody, phthalocyanine scaffold for intracellular delivery of photosensitizer to human papillomavirus-transformed cancer cells.
发表日期:2023 Dec
作者:
Elvin Peter Chizenga, Heidi Abrahamse
来源:
Artificial Cells Nanomedicine and Biotechnology
摘要:
在光动力疗法(PDT)中,光敏剂(PS)进入和吞噬细胞是一种被动过程,依赖于肿瘤组织由于其血管、LDL受体增加和淋巴引流减少而产生的增强渗透和滞留(EPR)效应。然而,随着对PDT耐药性的担忧不断增加,使用被动技术来施用PS变得越来越不可行。根据报道的耐药机制,有必要通过改变PS吸收和生物可利用性来改进PS的传输方式,以提高治疗效果。因此,在这项研究中,开发了一种具有特异性单克隆抗体(mAbs)的多功能光敏剂,用于人乳头状瘤病毒(HPV)转化的癌细胞的PDT。将PEG基金纳米颗粒(PEGy-AuNP)放在核心位置,然后将抗E6 mAbs和酞菁素绑定在一起。该化合物表现出PS的内化增强,从而产生了增强的PDT效果。尽管在体外已经证明了这种物质,但这项工作的目的是用于体内应用,并且根据观察到的数据提出了可能的体内模型结果。通过使PS更具生物可利用性,促进它们进入细胞,并通过细胞内结合来防止外流,这种策略可以减少细胞对PDT的抵抗。
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 in vivo. 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 in vitro, the substance in this work is intended for in vivo application, and conclusions are drawn to suggest possible outcomes for in vivo 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.