Publication:
Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment

Файлы
W3083803591.pdf(1.49 MB)
Дата
2020
Авторы
Shipunova, V. O.
Komedchikova, E. N.
Kotelnikova, P. A.
Zelepukin, I. V.
Kabashin, A. V.
Prasad, P. N.
Deyev, S. M.
Journal Title
Journal ISSN
Volume Title
Издатель
Научные группы
Организационные подразделения
OrgUnit Logo
Организационная единица
Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
Выпуск журнала
Аннотация
When combined with immunotherapy, image-guided targeted delivery of chemotherapeutic agents is a promising direction for combination cancer theranostics, but this approach has so far produced only limited success due to a lack of molecular targets on the cell surface and low therapeutic index of conventional chemotherapy drugs. Here, we demonstrate a synergistic strategy of combination immuno/chemotherapy in conditions of dual regioselective targeting, implying vectoring of two distinct binding sites of a single oncomarker (here, HER2) with theranostic compounds having la different mechanism of I action. We use: (i) PLGA nanoformulation, loaded with an imaging diagnostic fluorescent dye (Nile Red) and la chemotherapeutic drug (doxorubicin), and functionalized with affibody Z(HER2:342) (8 kDa); (ii) bifunctional genetically engineered DARP-LoPE (42 kDa) immunotoxin comprising of a low-immunogenic modification of therapeutic Pseudomonas exotoxin A (LOPE) and a scaffold targeting protein, DARPin9.29 (14 kDa). According to the proposed strategy, the first chemotherapeutic nanoagent is targeted by the affibody to subdomain III and 14 of HER2 with 60-fold specificity compared with nontargeted particles, while the second immunotoxin is effectively targeted by DARPin molecule to subdomain I of HER2. We demonstrate that this dual targeting strategy can enhance anticancer therapy of HER2-positive cells with a very strong synergy, which made possible 1000-fold decrease of effective drug concentration in vitro and a significant enhancement of HER2 cancer therapy compared to monotherapy in vivo. Moreover, this therapeutic combination prevented the appearance of secondary tumor nodes. Thus, the suggested synergistic strategy, utilizing dual targeting of the same oncomarker could give rise to efficient methods for aggressive tumors treatment.
Описание
Ключевые слова
Цитирование
Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment / Shipunova, VO [et al.] // ACS Nano. - 2020. - 14. - № 10. - P. 12781-12795. - 10.1021/acsnano.0c03421
URI
https://www.doi.org/10.1021/acsnano.0c03421
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85092561634&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000586793400035
 https://openrepository.mephi.ru/handle/123456789/22990
Коллекции
Публикации