title: Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin.
abstract: It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cellsin vitroand suppress the growth of HA-1 tumors and metastasesin vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors. However, Lactaptin, as with the majority of protein-based therapeutic drugs, is distributed evenly throughout the organism, which reduces its antitumor efficacy. To develop the targeted delivery of lactaptin, the present study selected tumor-specific peptides by screening a phage display peptide libraryin vivoon A/Sn strain mice with subcutaneously transplanted HA-1 cells. Two genetic constructs were made for the production of recombinant fusion proteins composed of RL2 and the selected tumor-targeting peptide.In vitroexperiments involving HA-1, MDA-MB-231 and MCF-7 cells cultures demonstrated that the fusion proteins induce apoptotic death in mouse and human tumor cells, as with RL2. Thein vivoexperiments involving the mouse HA-1 tumor model demonstrated that the tumor fluorescence intensity of the Cy5-fusion protein conjugates is higher than that of RL2-Cy5. As conjugation of the tumor-specific peptides to RL2 provided retention of RL2 in the tumor tissues, fusion proteins composed of lactaptin and peptides specific for human tumors are deemed promising to improve the antitumor efficiency of lactaptin.
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Anna Andreevna
authors.initials: AA
authors.lastname: Nemudraya
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Elena Vladimirovna
authors.initials: EV
authors.lastname: Kuligina
authors.affiliation: Department of Bioengineering, State Research Center of Virology and Biotechnology VECTOR, 630559 Koltsovo, Russia; Department of Biology, Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
authors.forename: Alexandr Alexeevich
authors.initials: AA
authors.lastname: Ilyichev
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Alexandr Sergeevich
authors.initials: AS
authors.lastname: Fomin
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Grigory Alexandrovich
authors.initials: GA
authors.lastname: Stepanov
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Anna Valentinovna
authors.initials: AV
authors.lastname: Savelyeva
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia; Department of Biology, Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
authors.forename: Olga Alexandrovna
authors.initials: OA
authors.lastname: Koval
authors.affiliation: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Vladimir Alexandrovich
authors.initials: VA
authors.lastname: Richter
keywords: apoptosis; fusion proteins; lactaptin; targeted delivery; tumor-specific peptides