FRET-based intracellular investigation of nanoprodrugs toward highly efficient anticancer drug delivery

• Published in: Nanoscale Vol. 12; no. 32; pp. 1671 - 16715
• Main Authors: Taemaitree, Farsai, Fortuni, Beatrice, Koseki, Yoshitaka, Fron, Eduard, Rocha, Susana, Hofkens, Johan, Uji-i, Hiroshi, Inose, Tomoko, Kasai, Hitoshi
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 20.08.2020
• Subjects: Antineoplastic Agents; Biocompatibility; Cancer; Drug Delivery Systems; Fluorescence Resonance Energy Transfer; In vivo methods and tests; Nanomedicine; Prodrugs; Toxicity
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/d0nr04910g

In order to overcome unpredictable side-effects and increased cytotoxicity of conventional carrier-based anticancer drug delivery systems, several systems that consist exclusively of the pure drug (or prodrug) have been proposed. The behavior and dynamics of these systems after entering cancer cells are, however, still unknown, hindering their progress towards in vivo and clinical applications. Here, we report a comprehensive in cellulo study of carrier-free SN-38 nanoprodrugs (NPDs), previously developed by our group. The work shows the intracellular uptake, localization, and degradation of the NPDs via FRET microscopy. Accordingly, new FRET-NPDs were chemically synthesized and characterized. Prodrug to drug conversion and therapeutic efficiency were also validated. Our work provides crucial information for the application of NPDs as drug delivery systems and demonstrates their outstanding potential as next-generation anticancer nanomedicines. FRET Nanoprodrugs (FRET-NPDs) were synthesized and internalized in cancer cells to study their intracellular dynamics and degradation.