Enhanced Intracellular Photosensitizer Uptake and Retention by Targeting Viral Oncoproteins in Human Papillomavirus Infected Cancer Cells and Cancer Stem Cells

Elvin Peter Chizenga, Heidi Abrahamse

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number647
JournalMolecules
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 2023

Keywords

  • E6 oncoproteins
  • SiHa cells
  • cancer stem cells (CSCs)
  • human papillomavirus (HPV)
  • immunogenic
  • non-side population (nSP)
  • photodynamic therapy (PDT)
  • side population (SP)
  • transformed

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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