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用于膀胱癌靶向成像与化疗的透明质酸共轭荧光探针屏蔽聚多巴胺纳米药物

Hyaluronic Acid-Conjugated Fluorescent Probe-Shielded Polydopamine Nanomedicines for Targeted Imaging and Chemotherapy of Bladder Cancer.

作者信息

Qiu Heping, Wang Jianwu, Zhi Yi, Yan Benhuang, Huang Yuandi, Li Jinjin, Shen Chongxing, Dai Linyong, Fang Qiang, Shi Chunmeng, Li Weibing

机构信息

Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing 400038, China.

出版信息

ACS Appl Mater Interfaces. 2023 Oct 11;15(40):46668-46680. doi: 10.1021/acsami.3c09564. Epub 2023 Sep 28.

Abstract

Bladder cancer is one of the most common malignancies in the urinary system, with high risk of recurrence and progression. However, the difficulty in detecting small tumor lesions and the lack of selectivity of intravesical treatment seriously affect the prognosis of patients with bladder cancer. In the present work, a nanoparticle-based delivery system with tumor targeting, high biocompatibility, simple preparation, and the ability to synergize imaging and therapy was fabricated. Specifically, this nanosystem consisted of the core of doxorubicin (DOX)-loaded polydopamine nanoparticles (PDD NPs) and the shell of hyaluronic acid (HA)-conjugated IR780 (HA-IR780). The HA-IR780-covered PDD NPs (HR-PDD NPs) demonstrated tumor targeting and visualization both in vitro and in vivo with properties of promoted cancer cell endocytosis and lysosomal escape, efficiently delivering drugs to the target site and exerting a killing effect on tumor cells. Encouragingly, intravesical instillation of HR-PDD NPs improved drug retention in the bladder and promoted its accumulation in tumor tissue, resulting in better tumor proliferation inhibition and apoptosis in an orthotopic bladder cancer model in rats. This study provides a promising strategy for the diagnosis and therapy of bladder cancer.

摘要

膀胱癌是泌尿系统最常见的恶性肿瘤之一,具有高复发和进展风险。然而,小肿瘤病变检测困难以及膀胱内治疗缺乏选择性严重影响膀胱癌患者的预后。在本研究中,制备了一种具有肿瘤靶向性、高生物相容性、制备简单且具备成像与治疗协同能力的基于纳米颗粒的递送系统。具体而言,该纳米系统由负载阿霉素(DOX)的聚多巴胺纳米颗粒(PDD NPs)核心和透明质酸(HA)共轭的IR780(HA-IR780)外壳组成。覆盖有HA-IR780的PDD NPs(HR-PDD NPs)在体外和体内均表现出肿瘤靶向性和可视化,具有促进癌细胞内吞作用和溶酶体逃逸的特性,能有效地将药物递送至靶位点并对肿瘤细胞发挥杀伤作用。令人鼓舞的是,在大鼠原位膀胱癌模型中,膀胱内灌注HR-PDD NPs可提高药物在膀胱中的保留率,并促进其在肿瘤组织中的蓄积,从而更好地抑制肿瘤增殖并诱导凋亡。本研究为膀胱癌的诊断和治疗提供了一种有前景的策略。

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