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

• Jiaxin Qin ^[3] ; Qing Liang ^[3] ; Guangyue Wang ^[1] ; Lin Hao ^[3] ; Xing Liu ^[3] ; Xinlei Wang ^[3] ; Zhengxiang Hu ^[4] ; Gaochuan Fang ^[2] ; Liang Xue ^[3] ; Yan Zhao ^[3] ; Rui Li ^[5] ; Qian Lv ^[5] ; Jiling Wen ^[6] ; Guosheng Yang ^[6] ; Conghui Han ^[3] ; Zhenduo Shi ^[3]
  1. [1] Bengbu Medical College

     Bengbu Medical College

     China

     
  2. [2] Jiangsu Normal University

     Jiangsu Normal University

     China

     
  3. [3] Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Jiefang South Road, No. 199, Xuzhou, Jiangsu, China
  4. [4] Graduate School of Jinzhou Medical College, Liaoning, China
  5. [5] Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, China
  6. [6] Department of Urology, Shanghai East Hospital Ji’an Hospital, Jiangxi, People’s Republic of China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 2 (February), 2023, págs. 375-383
• Idioma: inglés
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• Resumen

  • 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.