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

Abstract

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.

A light-responsive, self-immolative linker for controlled drug delivery via peptide- and protein-drug conjugates

“…Although the carbonochloridate intermediate reacts readily with amines, it can also react with alcohols and thiols. [33][34][35] For example, when 8 0 was treated in situ with 1-pyrenemethanol (PyrCH 2 OH), carbonate 10 was obtained in 50% yield.…”