Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative

• Published in: Bioorganic & medicinal chemistry letters Vol. 28; no. 20; pp. 3312 - 3314
• Main Authors: Minenkova, Olga, Vesci, Loredana, De Santis, Rita, Santapaola, Daniela, Cincinelli, Raffaella, Musso, Loana, Dallavalle, Sabrina, Giannini, Giuseppe
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.11.2018; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Avidin - metabolism; AvidinOX; Biotin; Biotin - analogs & derivatives; Biotin - chemical synthesis; Biotin - metabolism; Biotin - therapeutic use; Camptothecin; Camptothecin - analogs & derivatives; Camptothecin - chemical synthesis; Camptothecin - metabolism; Camptothecin - therapeutic use; Carcinoma - drug therapy; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Female; Gimatecan; Humans; Life Sciences & Biomedicine; Mice; Ovarian Neoplasms - drug therapy; Pharmacology & Pharmacy; Physical Sciences; Protein Binding; Science & Technology; Tumor xenograft; Tumor xenograft; Camptothecin; Biotin; Gimatecan; AvidinOX; CETUXIMAB; IN-VITRO; EFFICACY; RADIONUCLIDE THERAPY; ANTITUMOR-ACTIVITY; CANCER; BRACHYTHERAPY
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.09.017

AvidinOX, an oxidated form of avidin, provides stable fixation of biotinylated molecules in tissues. Here we investigated the possibility to hold a novel biotinylated gimatecan-derived camptothecin in AvidinOX-treated sites. When the biotinylate camptothecin ST8161AA1 was injected at suboptimal doses, in combination with AvidinOX, in mice bearing human tumors xenografted, a higher growth inhibition was observed compared to when it was administered alone. [Display omitted] •AvidinOX, a glycoprotein that in vivo maintaining a high affinity for biotin.•A biotinylated CPT (Gimatecan) can efficiently bind AvidinOX.•A versatile way to hold biotinylated chemotherapeutics in AvidinOX-treated sites.•Useful approach for the local treatment of inoperable tumors. Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.