Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg 2028, South Africa.
Molecules. 2023 Jan 8;28(2):647. doi: 10.3390/molecules28020647.
Immunogenic proteins in cancer are relevant targets for drug delivery. In Photodynamic Therapy (PDT), surface antigens have previously been used to deliver the photosensitizer (PS) to the tumor microenvironment for specific targeting. However, can we target intracellular antigens to achieve more than surface recognition? Can we possibly increase PS intracellular localization and prevent drug efflux at the same time? In this study, these questions were addressed by using a compound that can not only specifically recognize and bind to intracellular E6 oncoproteins in Human Papillomavirus (HPV)-Transformed cancer cells, but is also capable of enhancing transmembrane uptake using the cells' own active transport mechanisms. HPV-transformed SiHa cells were cultured in vitro, and the resistant subpopulation was isolated using Magnetic Activated Cell Sorting (MACS). PDT was performed on four different cell types with varying physiognomies in terms of HPV oncoprotein expression and physiological form. Results demonstrated that tagging PSs on a carrier molecule that specifically delivers the PS inside the cells that express the target proteins enhanced both cellular uptake and retention of the PS even in the presence of drug efflux proteins on resistant subpopulations. These findings provide insight into the possibility of preventing cell-mediated resistance to PDT.
癌症中的免疫原性蛋白是药物递送的相关靶点。在光动力疗法（PDT）中，表面抗原以前被用于将光敏剂（PS）递送到肿瘤微环境中以进行特异性靶向。但是，我们能否靶向细胞内抗原以实现超越表面识别的效果？我们是否可以同时增加 PS 的细胞内定位并防止药物外排？在这项研究中，通过使用一种既能特异性识别和结合 HPV 转化癌细胞内的 E6 癌蛋白，又能利用细胞自身的主动转运机制增强跨膜摄取的化合物，回答了这些问题。在体外培养 HPV 转化的 SiHa 细胞，并使用磁激活细胞分选（MACS）分离耐药亚群。对四种不同的细胞类型进行 PDT，这些细胞在 HPV 癌蛋白表达和生理形式方面具有不同的特征。结果表明，将 PS 标记在专门将 PS 递送到表达靶蛋白的细胞内的载体分子上，即使在耐药亚群中存在药物外排蛋白的情况下，也能增强 PS 的细胞摄取和保留。这些发现为预防细胞介导的 PDT 耐药性提供了新的思路。
