PMID- 36100735 OWN - NLM STAT- MEDLINE DCOM- 20230126 LR - 20230202 IS - 1699-3055 (Electronic) IS - 1699-048X (Linking) VI - 25 IP - 2 DP - 2023 Feb TI - Targeted delivery of nuclear targeting probe for bladder cancer using cyclic pentapeptide c(RGDfK) and acridine orange. PG - 375-383 LID - 10.1007/s12094-022-02938-0 [doi] AB - 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. CI - (c) 2022. The Author(s), under exclusive licence to Federacion de Sociedades Espanolas de Oncologia (FESEO). FAU - Qin, Jiaxin AU - Qin J AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Liang, Qing AU - Liang Q AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Wang, Guangyue AU - Wang G AD - Graduate School of Bengbu Medical College, Anhui, China. FAU - Hao, Lin AU - Hao L AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Liu, Xing AU - Liu X AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Wang, Xinlei AU - Wang X AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Hu, Zhengxiang AU - Hu Z AD - Graduate School of Jinzhou Medical College, Liaoning, China. FAU - Fang, Gaochuan AU - Fang G AD - School of Life Sciences, Jiangsu Normal University, Jiangsu, China. FAU - Xue, Liang AU - Xue L AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Zhao, Yan AU - Zhao Y AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Li, Rui AU - Li R AD - Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Lv, Qian AU - Lv Q AD - Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. FAU - Wen, Jiling AU - Wen J AD - Department of Urology, Shanghai East Hospital Ji'an Hospital, Jiangxi, People's Republic of China. AD - Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. FAU - Yang, Guosheng AU - Yang G AD - Department of Urology, Shanghai East Hospital Ji'an Hospital, Jiangxi, People's Republic of China. AD - Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. FAU - Han, Conghui AU - Han C AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. hanchdoctor@st.btbu.edu.cn. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. hanchdoctor@st.btbu.edu.cn. AD - School of Life Sciences, Jiangsu Normal University, Jiangsu, China. hanchdoctor@st.btbu.edu.cn. AD - Department of Urology, Heilongjiang Provincial Hospital, Heilongjiang, China. hanchdoctor@st.btbu.edu.cn. FAU - Shi, Zhenduo AU - Shi Z AUID- ORCID: 0000-0001-6185-2985 AD - Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China. zhenduoxuzhou@163.com. AD - Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China. zhenduoxuzhou@163.com. AD - School of Life Sciences, Jiangsu Normal University, Jiangsu, China. zhenduoxuzhou@163.com. LA - eng GR - 82004110/the National Natural Science Foundation of China/ GR - BE2020758/the Jiangsu Province Key Research and Development Program/ GR - BE2019637/the Jiangsu Province Key Research and Development Program/ GR - Xuzhou Health Education Research [2017] No.22/the Xuzhou Medical Outstanding Talents/ GR - CXTDA2017048/the Jiangsu Medical Innovation Team/ GR - KC19075/the Key Projects of Xuzhou Science and Technology Plan/ GR - KC21184/the Key Projects of Xuzhou Science and Technology Plan/ GR - 2018TD004/the Xuzhou clinical medicine expert team project/ GR - 202120104/the Jiangxi Province Health Commission Science and technology project/ PT - Journal Article DEP - 20220913 PL - Italy TA - Clin Transl Oncol JT - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico JID - 101247119 RN - F30N4O6XVV (Acridine Orange) RN - 0 (Fluorescent Dyes) RN - TDQ283MPCW (Eosine Yellowish-(YS)) SB - IM MH - Animals MH - Mice MH - *Acridine Orange MH - Fluorescent Dyes MH - *Urinary Bladder Neoplasms/drug therapy MH - Eosine Yellowish-(YS) MH - Kidney MH - Cell Line, Tumor OTO - NOTNLM OT - Cyclic pentapeptide RGD-containing peptides1 OT - In vivo imaging system5 OT - Laser scanning confocal microscopy4 OT - Photodynamic therapy3 OT - RGD-binding integrins2 EDAT- 2022/09/14 06:00 MHDA- 2023/01/27 06:00 CRDT- 2022/09/13 23:26 PHST- 2022/07/20 00:00 [received] PHST- 2022/08/30 00:00 [accepted] PHST- 2022/09/14 06:00 [pubmed] PHST- 2023/01/27 06:00 [medline] PHST- 2022/09/13 23:26 [entrez] AID - 10.1007/s12094-022-02938-0 [pii] AID - 10.1007/s12094-022-02938-0 [doi] PST - ppublish SO - Clin Transl Oncol. 2023 Feb;25(2):375-383. doi: 10.1007/s12094-022-02938-0. Epub 2022 Sep 13.