Type of pH sensitive linker reveals different time-dependent intracellular localization, in vitro and in vivo efficiency in alpha-fetoprotein...
Mollaev M., Gorokhovets N. V., Nikolskaya E., Faustova M., Zabolotsky A., Zhunina O., Sokol M., Zamulaeva I., Severin E. S., Yabbarov N.
International Journal of Pharmaceutics
Vol.559, P. 138-146
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1016/j.ijpharm.2018.12.073
Аннотация:
Despite the presence of a variety of modern anticancer drugs at the market, doxorubicin (Dox) is still widely used in antineoplastic therapy, although its administration causes severe side effects. To enhance specific activity of such molecules, various approaches have been exploited: targeted moieties like monoclonal antibodies, onco-specific proteins and peptides are utilized as specific vector molecules; environment sensitive linkers are exploited to facilitate transported drug release at the target point etc. Acid-labile linkers are frequently used in synthesis due to the ability to be cleaved inside specific cellular compartments with acidic environment, avoiding possible recycling mechanisms. Two types of conjugates containing different acid-labile linkers have been synthesized. In vitro efficiency of doxorubicin conjugates with recombinant receptor-binding domain of human alpha-fetoprotein (3dAFPpG) synthesized with use of cis-aconitic anhydride (CAA) and linker based on succini
Ключевые слова:
Acid-labile linkers; Alpha-fetoprotein 3rd domain; Doxorubicin; Drug delivery; Tumor targeting
3 (2 pyridyldithio)propionate; 3 (2 pyridyldithio)propionic acid hydrazide; acid; aconitic anhydride; alpha fetoprotein; anthracycline; doxorubicin; recombinant receptor; unclassified drug; alpha fetoprotein; antineoplastic agent; antineoplastic antibiotic; doxorubicin; animal cell; antineoplastic activity; Article; cytotoxicity; drug conjugation; endosome; female; flow cytometry; human; human cell; in vitro study; in vivo study; intracellular space; lysosome; MCF-7 cell line; mouse; nonhuman; pH; priority journal; SK-OV-3 cell line; animal; Bagg albino mouse; chemistry; drug delivery system; metabolism; procedures; alpha-Fetoproteins; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Doxorubicin; Drug Delivery Systems; Female; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Mice; Mice, Inbred BALB C
Язык текста: Английский
ISSN: 1873-3476
Mollaev M.
Gorokhovets N. V. Neonila Vasilyevna 1956-
Nikolskaya E.
Faustova M.
Zabolotsky A.
Zhunina O.
Sokol M.
Zamulaeva I.
Severin E. S. Evgenij Sergeevich 1934-
Yabbarov N.
Моллаев М.
Гороховец Н. В. Неонила Васильевна 1956-
Николскайа Е.
Фаустова М.
Заболоцкy А.
Жунина О.
Сокол М.
Замулаева И.
Северин Е. С. Евгений Сергеевич 1934-
Яббаров Н.
Type of pH sensitive linker reveals different time-dependent intracellular localization, in vitro and in vivo efficiency in alpha-fetoprotein receptor targeted doxorubicin conjugate
Type of pH sensitive linker reveals different time-dependent intracellular localization, in vitro and in vivo efficiency in alpha-fetoprotein...
Текст визуальный непосредственный
International Journal of Pharmaceutics
Elsevier Science Publisher B.V.
Vol.559 P. 138-146
2019
Статья
Acid-labile linkers Alpha-fetoprotein 3rd domain Doxorubicin Drug delivery Tumor targeting
3 (2 pyridyldithio)propionate 3 (2 pyridyldithio)propionic acid hydrazide acid aconitic anhydride alpha fetoprotein anthracycline doxorubicin recombinant receptor unclassified drug alpha fetoprotein antineoplastic agent antineoplastic antibiotic doxorubicin animal cell antineoplastic activity Article cytotoxicity drug conjugation endosome female flow cytometry human human cell in vitro study in vivo study intracellular space lysosome MCF-7 cell line mouse nonhuman pH priority journal SK-OV-3 cell line animal Bagg albino mouse chemistry drug delivery system metabolism procedures alpha-Fetoproteins Animals Antibiotics, Antineoplastic Antineoplastic Agents Doxorubicin Drug Delivery Systems Female Humans Hydrogen-Ion Concentration MCF-7 Cells Mice Mice, Inbred BALB C
Despite the presence of a variety of modern anticancer drugs at the market, doxorubicin (Dox) is still widely used in antineoplastic therapy, although its administration causes severe side effects. To enhance specific activity of such molecules, various approaches have been exploited: targeted moieties like monoclonal antibodies, onco-specific proteins and peptides are utilized as specific vector molecules; environment sensitive linkers are exploited to facilitate transported drug release at the target point etc. Acid-labile linkers are frequently used in synthesis due to the ability to be cleaved inside specific cellular compartments with acidic environment, avoiding possible recycling mechanisms. Two types of conjugates containing different acid-labile linkers have been synthesized. In vitro efficiency of doxorubicin conjugates with recombinant receptor-binding domain of human alpha-fetoprotein (3dAFPpG) synthesized with use of cis-aconitic anhydride (CAA) and linker based on succini