Penetration efficiency of antitumor agents in ovarian cancer spheroids: The case of recombinant targeted toxin DARPin-LoPE and the chemotherapy...
Sokolova E., Kutova O., Grishina A. N., Pospelov A., Guryev E., Schulga A., Deev S. M., Balalaeva I. V.
Pharmaceutics
Vol.11, Issue5, Num.219
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.3390/pharmaceutics11050219
Аннотация:
The efficiency of delivering a therapeutic agent into a tumor is among the crucial factors determining the prospects for its clinical use. This problem is particularly acute in the case of targeted antitumor agents since many of them are high-molecular-weight compounds. In this work, the penetration of therapeutic agents of two distinct molecular weights into the spheroids of ovarian adenocarcinoma overexpressing human epidermal growth factor receptor 2 (HER2) was studied. It was shown that the low-molecular-weight chemotherapy drug, doxorubicin (~0.5 kDa), effectively penetrates through almost the entire depth of a 300 to 400 µm spheroid, while the penetration depth of the HER2-specific recombinant targeted toxin, DARPin-LoPE (~42 kDa), is only a few surface layers of cells and does not exceed 70 µm. The low penetration of the targeted toxin into spheroid was shown along with a significant decrease in its efficiency against the three-dimensional tumor spheroid as compared with the two
Ключевые слова:
DARPin; Drug penetration into tumor; HER2; Pseudomonas exotoxin A; Spheroid; Targeted therapy; Targeted toxin
antineoplastic agent; bovine serum albumin; desmoglein 2; doxorubicin; epidermal growth factor receptor; epidermal growth factor receptor 2; Pseudomonas exotoxin; Article; cell viability; cytotoxicity; drug delivery system; drug efficacy; drug penetration; female; flow cytometry; human; IC50; immunogenicity; monolayer culture; ovary adenocarcinoma; ovary cancer; prospective study; tumor microenvironment; tumor spheroid
Язык текста: Английский
ISSN: 1999-4923
Sokolova E.
Kutova O.
Grishina A. N. Alena Nikolaevna 1987-
Pospelov A.
Guryev E.
Schulga A.
Deev S. M. Sergej Mikhaylovich 1951-
Balalaeva I. V. Irina Vladimirovna 1978-
Соколова Е.
Кутова О.
Гришина А. Н. Алена Николаевна 1987-
Поспелов А.
Гурьев Е.
Счулга А.
Деев С. М. Сергей Михайлович 1951-
Балалаева И. В. Ирина Владимировна 1978-
Penetration efficiency of antitumor agents in ovarian cancer spheroids: The case of recombinant targeted toxin DARPin-LoPE and the chemotherapy drug, doxorubicin
Penetration efficiency of antitumor agents in ovarian cancer spheroids: The case of recombinant targeted toxin DARPin-LoPE and the chemotherapy...
Текст визуальный непосредственный
Pharmaceutics
Vol.11, Issue5 Num.219
2019
Статья
DARPin Drug penetration into tumor HER2 Pseudomonas exotoxin A Spheroid Targeted therapy Targeted toxin
antineoplastic agent bovine serum albumin desmoglein 2 doxorubicin epidermal growth factor receptor epidermal growth factor receptor 2 Pseudomonas exotoxin Article cell viability cytotoxicity drug delivery system drug efficacy drug penetration female flow cytometry human IC50 immunogenicity monolayer culture ovary adenocarcinoma ovary cancer prospective study tumor microenvironment tumor spheroid
The efficiency of delivering a therapeutic agent into a tumor is among the crucial factors determining the prospects for its clinical use. This problem is particularly acute in the case of targeted antitumor agents since many of them are high-molecular-weight compounds. In this work, the penetration of therapeutic agents of two distinct molecular weights into the spheroids of ovarian adenocarcinoma overexpressing human epidermal growth factor receptor 2 (HER2) was studied. It was shown that the low-molecular-weight chemotherapy drug, doxorubicin (~0.5 kDa), effectively penetrates through almost the entire depth of a 300 to 400 µm spheroid, while the penetration depth of the HER2-specific recombinant targeted toxin, DARPin-LoPE (~42 kDa), is only a few surface layers of cells and does not exceed 70 µm. The low penetration of the targeted toxin into spheroid was shown along with a significant decrease in its efficiency against the three-dimensional tumor spheroid as compared with the two