Targeted delivery of nuclear targeting probe for bladder cancer using cyclic pentapeptide c(RGDfK) and acridine orange.

Autor: Qin J; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Liang Q; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Wang G; Graduate School of Bengbu Medical College, Anhui, China., Hao L; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Liu X; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Wang X; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Hu Z; Graduate School of Jinzhou Medical College, Liaoning, China., Fang G; School of Life Sciences, Jiangsu Normal University, Jiangsu, China., Xue L; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Zhao Y; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Li R; Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Lv Q; Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, China., Wen J; Department of Urology, Shanghai East Hospital Ji'an Hospital, Jiangxi, People's Republic of China.; Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China., Yang G; Department of Urology, Shanghai East Hospital Ji'an Hospital, Jiangxi, People's Republic of China.; Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China., Han C; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. hanchdoctor@st.btbu.edu.cn.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. hanchdoctor@st.btbu.edu.cn.; School of Life Sciences, Jiangsu Normal University, Jiangsu, China. hanchdoctor@st.btbu.edu.cn.; Department of Urology, Heilongjiang Provincial Hospital, Heilongjiang, China. hanchdoctor@st.btbu.edu.cn., Shi Z; Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. zhenduoxuzhou@163.com.; Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. zhenduoxuzhou@163.com.; School of Life Sciences, Jiangsu Normal University, Jiangsu, China. zhenduoxuzhou@163.com.
Jazyk: angličtina
Zdroj: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2023 Feb; Vol. 25 (2), pp. 375-383. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1007/s12094-022-02938-0
Abstrakt: Purpose: Both cyclic pentapeptide c(RGDfK) and acridine orange (AO) exhibit antitumor effects and cell permeability. This study aimed to evaluate the nuclear targeting efficiency and safety of the nuclear targeting probe for bladder cancer (BCa) synthesized by c(RGDfK) and AO.
Methods: The nuclear targeting probe AO-(cRGDfK) 2 was synthesized from AO hydrochloride, azided c(RGDfK), and a near-infrared skeleton synthesized via click chemistry reactions. The effect of the AO-(cRGDfK) 2 probe on cell viability was assessed in BCa 5637 cells. The tumor cell targeting efficacy of the AO-(cRGDfK) 2 probe was evaluated in BCa cells in vitro and in tumor-bearing mice in vivo. Nuclear-specific accumulation of fluorescence probe in BCa tumor cells was evaluated using laser scanning confocal microscopy (LSCM). Hematoxylin and eosin staining was performed to detect histopathological changes in the spleen, heart, liver, and kidney.
Results: The AO-(cRGDfK) 2 probe did not cause a significant reduction in cell viability. LSCM analysis showed that AO-(cRGDfK) 2 exhibited nuclear-specific ambulation in BCa cells and was not accumulated in 293T cells. Also, this probe efficiently targeted tumor cells in the serum and urine samples. In vivo imaging system of tumor-bearing mice showed that ~ 80% percent of fluorescence signal was accumulated in the tumor sites. The probe did not change histopathology in the heart, liver, spleen, and kidney in tumor-bearing mice after the 21-day treatment.
Conclusions: The AO-(cRGDfK) 2 probe exhibited nuclear-specific accumulation in BCa cells without cytotoxicity, which provides an innovative alternative to improve anticancer therapy for BCa.
(© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)
Databáze: MEDLINE
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