Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Modular Nanotransporters Delivering Biologically Active Molecules to the Surface of Mitochondria

Version 1 : Received: 6 November 2023 / Approved: 6 November 2023 / Online: 7 November 2023 (02:49:52 CET)

A peer-reviewed article of this Preprint also exists.

Khramtsov, Y.V.; Ulasov, A.V.; Slastnikova, T.A.; Rosenkranz, A.A.; Lupanova, T.N.; Georgiev, G.P.; Sobolev, A.S. Modular Nanotransporters Delivering Biologically Active Molecules to the Surface of Mitochondria. Pharmaceutics 2023, 15, 2687. Khramtsov, Y.V.; Ulasov, A.V.; Slastnikova, T.A.; Rosenkranz, A.A.; Lupanova, T.N.; Georgiev, G.P.; Sobolev, A.S. Modular Nanotransporters Delivering Biologically Active Molecules to the Surface of Mitochondria. Pharmaceutics 2023, 15, 2687.

Abstract

Treatment of various diseases, in particular cancer, usually needs targeting 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, demonstrates significantly higher photocytotoxicity than chlorine e6 alone. We assume that MNTs of this kind can improve efficiency of therapeutic photosensitizers and radionuclides emitting short-range particles.

Keywords

modular nanotransporters; Keap1; intracellular delivery; CETSA; FLIM-FRET; FLIM; thermophoresis; chlorine e6; targeting to mitochondria

Subject

Biology and Life Sciences, Life Sciences

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