{
  "abstract": "Background CD44 overexpression in colorectal cancer (CRC) makes it an ideal precision delivery target. Conventional photodynamic therapy (PDT) lacks tumor selectivity and relies on apoptosis, a pathway defective in drug-resistant cells. We developed a CD44-targeting peptide A6-modified phage carrying photosensitizer TVP (A6-Sp-TVP) to investigate its targeted PDT efficacy and underlying cell death mechanisms in CRC cells.Methods A6-Sp-TVP was constructed by conjugating A6 peptide to a phage vector loaded with TVP. Cellular uptake was evaluated in CD44-high SW480 and CD44-low HCT15 cells. Cells were treated with blue light alone or A6-Sp-TVP followed by blue light. Cell viability, ROS production, ultrastructural changes, ferroptosis, paraptosis, and ATF4 expression were evaluated.Results A6-Sp-TVP exhibited significantly higher uptake in SW480 versus HCT15 cells, confirming CD44-specific targeting ( IDDF2026-ABS-0143 Figure 1. Cellular uptake of A6-Sp-TVP). A6-Sp-TVP-PDT achieved markedly enhanced killing compared to blue light alone. Strikingly, TEM revealed that while blue light alone only caused mitochondrial swelling (apoptosis), A6-Sp-TVP-PDT induced additional ER expansion (paraptosis) and shrunken mitochondria (ferroptosis). Consistently, A6-Sp-TVP-PDT increased lipid peroxidation, depleted GSH, upregulated CHAC1, and downregulated GPX4. Notably, ATF4 expression was substantially elevated following targeted PDT (IDDF2026-ABS-0143 Figure 2. A6-Sp TVP-mediated PDT induces ferroptosis and paraptosis in CRC cells).Conclusions The CD44-targeted system enables specific photosensitizer enrichment in CD44-high CRC cells. A6-Sp-TVP-PDT expands cell death from single apoptosis to ferroptosis/paraptosis (circumventing apoptosis resistance) with ATF4 as a key regulator, offering a novel strategy to overcome apoptosis-dependent chemoresistance in CRC.Abstract IDDF2026-ABS-0143 Figure 1Abstract IDDF2026-ABS-0143 Figure 2",
  "authors": [
    {
      "affiliations": [
        "Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China"
      ],
      "name": "Yuqing Wang"
    },
    {
      "affiliations": [
        "Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China"
      ],
      "name": "Min Li"
    },
    {
      "affiliations": [
        "Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China"
      ],
      "name": "Shenglan Yang"
    }
  ],
  "title": "IDDF2026-ABS-0143 CD44-targeted phage-mediated photodynamic therapy induces multi-modal cell death to overcome chemoresistance in colorectal cancer",
  "uid": "f95c85f4-4129-5e04-8675-662d1fab5558"
}