Department of Biotechnology

Targeted delivery of antitumor and diagnostic agents based on conjugates with ligand proteins, nanoparticles, and natural compounds

Description

The project integrates fundamental and applied research in the field of targeted delivery of biologically active compounds. Conjugates of antitumor drugs (doxorubicin, esperamicin A1), photosensitizers (phthalocyanines, chlorins), and nanoparticles (agaricic acid nanoparticles) with ligand proteins — alpha-fetoprotein and epidermal growth factor — are studied. The cytotoxic and antitumor activity of the obtained conjugates, their accumulation, and intracellular distribution in sensitive and resistant tumor cells are investigated. A separate direction is devoted to the study of redox signaling, the structural organization of bacterial cellulose, and the biological activity of agaricic acid nanoparticles

Goal

Development and study of targeted delivery systems for antitumor and diagnostic agents based on conjugates with ligand proteins, nanoparticles, and natural compounds to improve the efficacy of therapy and overcome drug resistance of tumor cells

Key objectives

1. Synthesis and characterization of doxorubicin conjugates with epidermal growth factor and its receptor-binding fragment
2. Study of the cytotoxic activity, accumulation, and intracellular distribution of anthracycline antibiotics and their conjugates in sensitive and resistant MCF-7 cells
3. Investigation of the antitumor activity of alpha-fetoprotein conjugates with doxorubicin and esperamicin A1 in vitro and in vivo
4. Study of the cytotoxic action of alpha-fetoprotein and epidermal growth factor conjugates with photosensitizers
5. Assessment of the biological activity of agaricic acid nanoparticles against human hepatoma HepG2 cells
6. Study of redox signaling and adaptive redox switches through oxidative and nitrosative protein modifications
7. Investigation of the structural organization of bacterial cellulose

Partner organizations

• Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
• Orekhovich Research Institute of Biomedical Chemistry
• Sechenov University
• Lomonosov Moscow State University

Publications

• Gudkova OI, Demchenko AG, Shvets AV, Kuryakov VN, Sedyakina NE, Lyundup AV, Feldman NB, Gromovykh TI, Lutsenko SV. Biological Activity of Agaricinic Acid Nanoparticles against Human Hepatoma HepG2 Cells. Bull Exp Biol Med. 2020 Aug;169(4):508-511. doi: 10.1007/s10517-020-04919-1.
• Lutsenko SV, Feldman NB, Severin SE. Cytotoxic and antitumor activities of doxorubicin conjugates with the epidermal growth factor and its receptor-binding fragment. J Drug Target. 2002 Nov;10(7):567-71. doi: 10.1080/1061186021000038058
• Lutsenko SV, Feldman NB, Gumanov SG, Rodina AV, Severin SE. Cytotoxic activity, accumulation, and intracellular distribution of anthracycline antibiotics and their conjugates with the epidermal growth factor in sensitive and resistant MCF-7 cells. Biochemistry (Mosc). 2000 Nov;65(11):1299-304
• Lutsenko SV, Feldman NB, Finakova GV, Gukasova NV, Petukhov SP, Posypanova GA, Skryabin KG, Severin SE. Antitumor activity of alpha fetoprotein and epidermal growth factor conjugates in vitro and in vivo. Tumour Biol. 2000 Nov-Dec;21(6):367-74. doi: 10.1159/000030142
• Feldman NB, Kiselev SM, Gukasova NV, Posypanova GA, Lutsenko SV, Severin SE. Antitumor activity of alpha-fetoprotein conjugate with doxorubicin in vitro and in vivo. Biochemistry (Mosc). 2000 Aug;65(8):967-71
• Savitsky AA, Gukasova NV, Gumanov SG, Feldman NB, Luk'yanets EA, Mironov AF, Yakubovskaya RI, Lutsenko SV, Severin SE. Cytotoxic action of conjugates of alpha-fetoprotein and epidermal growth factor with photoheme, chlorines, and phthalocyanines. Biochemistry (Mosc). 2000 Jun;65(6):732-6.
• Severin SE, Posypanova GA, Sotnichenko AI, Moskaleva EIu, Fel'dman NB, Grigor'ev MI, Severin ES, Petrov RV. [Antitumor activity of a covalent conjugate of the endiene antibiotic esperamicin A1 with human alpha-fetoprotein]. Dokl Akad Nauk. 1999 Jun;366(4):561-4.
• Lutsenko SV, Feldman NB, Finakova GV, Posypanova GA, Severin SE, Skryabin KG, Kirpichnikov MP, Lukyanets EA, Vorozhtsov GN. Targeting phthalocyanines to tumor cells using epidermal growth factor conjugates. Tumour Biol. 1999 Jul-Aug;20(4):218-24. doi: 10.1159/000030066
• Sotnichenko AI, Severin SE, Posypanova GA, Feldman NB, Grigor'ev MI, Severin ES, Petrov RV. Water-soluble 2,3,7,8-tetrachlorodibenzo-p-dioxin complex with human alpha-fetoprotein: properties, toxicity in vivo and antitumor activity in vitro. FEBS Lett. 1999 Apr 30;450(1-2):49-51. doi: 10.1016/s0014-5793(99)00440-8.