{
  "abstract": "Bioorthogonal pretargeting offers a modular approach to targeted photodynamic therapy (PDT), but its advantages over conventional ligand-photosensitizer conjugates remain insufficiently explored. Here, we aimed to directly compare preformed biotin-containing conjugates with sequential biotin-mediated bioorthogonal delivery. DFT calculations were used to guide the design of new tetrazine dienes with tuned electronic properties for inverse-electron-demand Diels-Alder (IEDDA) chemistry. The selected tetrazines were synthesized and paired with BCN- and s-TCO-functionalized chlorin photosensitizers, and their reactivity was characterized by second-order rate constants and photophysical measurements. In vitro, sequential pretargeting produced substantially higher intracellular fluorescence than administration of preformed 1:1 ligation products; however, this advantage did not translate into enhanced photodynamic activity. Moreover, neither accumulation nor PDT efficacy consistently correlated with SLC5A6 expression in SMVT-high SK-BR-3 versus SMVT-low MDA-MB-231 cells. Free-biotin competition produced heterogeneous, combination-dependent effects, indicating that SMVT is unlikely to be the sole determinant of uptake.",
  "abstract_shown": true,
  "affiliations": [
    "Lobachevsky State University of Nizhny Novgorod, Gagarina av. 23, Nizhny Novgorod, Russian Federation, 603950",
    "Chemistry Department of Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, Russia, 119991"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Petar Jankovic",
      "orcid": "0009-0008-2492-4626"
    },
    {
      "affs": [
        0
      ],
      "name": "Anastasia A. Gorokhova"
    },
    {
      "affs": [
        0
      ],
      "name": "Ilya A. Shmyrov"
    },
    {
      "affs": [
        0
      ],
      "name": "Jana M. Svetlova"
    },
    {
      "affs": [
        0
      ],
      "name": "Natalia S. Kuzmina",
      "orcid": "0000-0001-9609-1717"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexander V. Nyuchev",
      "orcid": "0000-0002-0460-0543"
    },
    {
      "affs": [
        0
      ],
      "name": "Sergey S. Nikolashin"
    },
    {
      "affs": [
        0
      ],
      "name": "Maxim N. Miheenko"
    },
    {
      "affs": [
        1
      ],
      "name": "Elena G. Zavyalova"
    },
    {
      "affs": [
        0
      ],
      "name": "Elizaveta M. Pnachina"
    },
    {
      "affs": [
        0
      ],
      "name": "Lubov V. Krylova"
    },
    {
      "affs": [
        0
      ],
      "name": "Irina V. Balalaeva",
      "orcid": "0000-0002-3245-3907"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexey Yu. Fedorov",
      "orcid": "0000-0003-4889-8617"
    },
    {
      "affs": [
        0
      ],
      "name": "Vasilii F. Otvagin",
      "orcid": "0000-0001-6015-099X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cartsh6m5pefc.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008548/v1",
  "fulltext_url": null,
  "id": "cartsh6m5pefc",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008548/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Photodynamic Therapy Research Studies"
    ]
  ],
  "openalex": "W7211998066",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008548/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/cartsh6m5pefc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15008548",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008548/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Photodynamic Therapy Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Is Bioorthogonal Pretargeting Superior to Conventional Targeted Photosensitizers? A Comparative Study of Chlorin Delivery Using Biotin Vectors",
  "title_text": "Is Bioorthogonal Pretargeting Superior to Conventional Targeted Photosensitizers? A Comparative Study of Chlorin Delivery Using Biotin Vectors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/cartsh6m5pefc",
  "venue": "ChemRxiv",
  "versions": []
}