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

doi:10.3390/pharmaceutics15122687

Modular Nanotransporters Delivering Biologically Active Molecules to the Surface of Mitochondria

Pharmaceutics. 2023 Nov 27;15(12):2687. doi: 10.3390/pharmaceutics15122687.

Authors

Yuri V Khramtsov¹, Alexey V Ulasov¹, Tatiana A Slastnikova¹, Andrey A Rosenkranz^{1

2}, Tatiana N Lupanova¹, Georgii P Georgiev¹, Alexander S Sobolev^{1

2}

Affiliations

¹ Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia.
² Faculty of Biology, Lomonosov Moscow State University, 1-12 Leninskie Gory St., 119234 Moscow, Russia.

Abstract

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.

Keywords: CETSA; FLIM; FLIM-FRET; Keap1; chlorin e6; intracellular delivery; modular nanotransporters; targeting to mitochondria; thermophoresis.

Grants and funding

22-14-00094/Russian Science Foundation