Улучшение противоопухолевой терапии за счет применения самонаводящегося петита PL3, проникающего в клетку
Авторы
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Dhafir Masheta
College of Pharmacy, University of Babylon
https://orcid.org/0000-0003-0333-5407
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Shafq Al-Azzawi
College of Pharmacy, University of Babylon
https://orcid.org/0000-0003-4243-0255
DOI:
https://doi.org/10.18413/rrpharmacology.9.10028Аннотация
Введение. Самонаводящиеся пептиды привлекли большое внимание для разработки неинвазивных и таргетных систем доставки лекарственных средств с целью минимизации системной токсичности лекарственных средств, предназначенных для лечения опухолей, и повышения их биодоступности. Это исследование направлено на улучшение противоопухолевого действия лекарственного средства, предназначенного для лечения рака предстательной железы, путем таргетной доставки лекарственного средства в системе носителе, состоящей из пептида PL3, проникающего в клетку путем самонаведения в опухоль.
Материалы и методы: Система доставки лекарственного средства была сконструирована с помощью твердофазного синтеза пептида, а затем охарактеризована с помощью масс-спектра и высокоэффективной жидкостной хроматографии. Была проведена оценка жизнеспособности клеток для оценки их цитотоксичности как в отношении опухолевых (клетки рака предстательной железы), так и в отношении нормальных клеток, а для исследования интернализации использовались конфокальный лазерный сканирующий микроскоп и проточный цитометр. Для проверки эффективности системы доставки лекарственного средства, содержащей лекарственное средство, был проведен биохимический анализ ингибирования фермента на целевом ферменте дигидрофолатредуктазе.
Результаты и их обсуждение. Полученные данные подтвердили успешный синтез и введение лекарственного средства в систему-носитель и продемонстрировали его высокую эффективность в отношении цитотоксического действия и ингибирования дигидрофолатредуктазы со значительным клеточным поглощением в клетках рака предстательной железы.
Заключение: лекарственное средство было доставлено к клеткам-мишеням рака предстательной железы с помощью PL3-функциональной системой доставки лекарственных средств, и позволило локализовать лекарственное средство в опухолевых клетках, не затрагивая нормальные клетки. Таким образом, результаты исследования подчеркнули важность систем доставки лекарственных средств в лечении опухолей.
Графическая аннотация
Ключевые слова:
химиотерапия рака, пептид, проникающий в клетку, система доставки лекарственных средств, рак предстательной железы, самонаправляющийся пептид в опухольБиблиографические ссылки
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