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. 2020 Oct-Dec;12(4):47-56.
doi: 10.32607/actanaturae.11049.

The Delivery of Biologically Active Agents into the Nuclei of Target Cells for the Purposes of Translational Medicine

A S Sobolev  1   2
Affiliations

The Delivery of Biologically Active Agents into the Nuclei of Target Cells for the Purposes of Translational Medicine

A S Sobolev. Acta Naturae. 2020 Oct-Dec.

Abstract

Development of vehicles for the subcellular targeted delivery of biologically active agents is very promising for the purposes of translational medicine. This review summarizes the results obtained by researchers from the Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology RAS, which allowed them to design the core technology: modular nanotransporters. This approach ensures high efficacy and cell specificity for different anti-cancer agents, as they are delivered into the most vulnerable subcellular compartment within the cells of interest and makes it possible for antibody mimetics to penetrate into a compartment of interest within the target cells ("diving antibodies"). Furthermore, polyplexes, complexes of polycationic block copolymers of DNA, have been developed and characterized. These complexes are efficient both in vitro and in vivo and demonstrate predominant transfection of actively dividing cells.

Keywords: antibody mimetics; drug delivery; gene therapy; modular nanotransporters; photodynamic therapy; polyplexes; radiotherapy.

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Figures

Fig. 1
Fig. 1
Modular nanotransporters (A) and the schematic representation (B) of how they are transported into the cell nucleus (after [15])
Fig. 2
Fig. 2
Subcellular MNTEGF localization within A431 human epidermoid carcinoma cells (after [9] with permission). The A431 cells were incubated for 4 h with MNTEGF in a culture medium, then washed and incubated in the medium without MNTEGF. (A) – immunocytochemical detection of MNTEGF, (B) – nuclear DNA detection with ToPro-3 in the same group of A431 cells
Fig. 3
Fig. 3
Administration of 111In-MNTEGF into subcutaneous tumors (EJ human bladder cancer) transplanted to immunodeficient Balb/c nu/nu mice (after [20] with changes): (A) – SPECT/CT visualization of radioactivity retention within the tumor; (B) – the kinetics of radioactivity retention by the tumor and normal tissues; (C) – antitumor efficiency of 111In-MNTEGF after intratumoral administration
Fig. 4
Fig. 4
Polyplex penetration into the tumor (after [62] with permission). (A) – control; (B) – after inhibition of collagen I production with losartan
See this image and copyright information in PMC

References

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