Modular Nanotransporters Delivering Biologically Active Molecules to the Surface of Mitochondria
Yuri V. Khramtsov,
Alexey V. Ulasov,
Tatiana A. Slastnikova,
Andrey A. Rosenkranz,
Tatiana N. Lupanova,
Georgii P. Georgiev,
Alexander S. Sobolev
Affiliations
Yuri V. Khramtsov
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Alexey V. Ulasov
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Tatiana A. Slastnikova
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Andrey A. Rosenkranz
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Tatiana N. Lupanova
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Georgii P. Georgiev
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Alexander S. Sobolev
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia
Treatment of various diseases, in particular cancer, usually requires the targeting of biologically active molecules at a selected subcellular compartment. We modified our previously developed modular nanotransporters (MNTs) for targeting mitochondria. The new MNTs are capable of binding to the protein predominantly localized on the outer mitochondrial membrane, Keap1. These MNTs possessing antiKeap1 monobody co-localize with mitochondria upon addition to the cells. They efficiently interact with Keap1 both in solution and within living cells. A conjugate of the MNT with a photosensitizer, chlorin e6, demonstrated significantly higher photocytotoxicity than chlorin e6 alone. We assume that MNTs of this kind can improve efficiency of therapeutic photosensitizers and radionuclides emitting short-range particles.
