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Proceedings Paper

Recombinant modular transporters on the basis of epidermal growth factor for targeted intracellular delivery of photosensitizers
Author(s): Dinara G. Gilyazova; Andrey A. Rosenkranz; Pavel V. Gulak; Vladimir G. Lunin; Olga V. Sergienko; Mikhail A. Grin; Andrey F. Mironov; Andrey B. Rubin; Alexander S. Sobolev
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Paper Abstract

The search for new pharmaceuticals has raised interest in locally-acting drugs which act over short distances within the cell, and for which different cell compartments have different sensitivities. Thus, photosensitizers used in anti-cancer therapy should be transported to the most sensitive subcellular compartments where their action is most pronounced. Earlier, we described the effects of bacterially expressed modular recombinant transporters for photosensitizers comprising a-melanocyte-stimulating hormone as an internalizable, cell-specific ligand, an optimized nuclear localization sequence, an Escherichia coli hemoglobin-like protein as a carrier, and an endosomolytic amphipathic polypeptide. These transporters delivered photosensitizers into the murine melanoma cells nuclei to result in cytotoxic effects 2 orders of magnitude greater than those of nonmodified photosensitizers. Here we describe new transporters possessing the same modules except for a ligand that is replaced with epidermal growth factor specific for other cancer cell types. The new transporter modules retained their functional activities within the chimera, this transporter delivered photosensitizers into the human carcinoma cells nuclei to result in photocytotoxic effects almost 3 orders of magnitude greater than those of nonmodified photosensitizers. The obtained results show that ligand modules of such transporters are interchangeable, meaning that they can be tailored for particular applications.

Paper Details

Date Published: 7 December 2006
PDF: 10 pages
Proc. SPIE 5973, Current Research on Laser Use in Oncology: 2000-2004, 59730E (7 December 2006); doi: 10.1117/12.640049
Show Author Affiliations
Dinara G. Gilyazova, Moscow State Univ. (Russia)
Andrey A. Rosenkranz, Moscow State Univ. (Russia)
Institute of Gene Biology, RAS (Russia)
Pavel V. Gulak, Institute of Gene Biology, RAS (Russia)
Vladimir G. Lunin, Institute of Gene Biology, RAS (Russia)
Gamaleya Institute of Epidemiology and Microbiology, RAMS (Russia)
Olga V. Sergienko, Institute of Gene Biology, RAS (Russia)
Gamaleya Institute of Epidemiology and Microbiology, RAMS (Russia)
Mikhail A. Grin, Moscow State Academy of Fine Chemical Technology (Russia)
Andrey F. Mironov, Moscow State Academy of Fine Chemical Technology (Russia)
Andrey B. Rubin, Moscow State Univ. (Russia)
Alexander S. Sobolev, Moscow State Univ. (Russia)
Institute of Gene Biology, RAS (Russia)


Published in SPIE Proceedings Vol. 5973:
Current Research on Laser Use in Oncology: 2000-2004
Andrei V. Ivanov; Mishik A. Kazaryan, Editor(s)

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