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Phosphorus dendrimer-based copper(II) complexes enable ultrasound-enhanced tumor theranostics
Nano Today ( IF 13.2 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.nantod.2020.100899
Yu Fan , Lizhou Lin , Fangfang Yin , Yu Zhu , Mingwu Shen , Han Wang , Lianfang Du , Serge Mignani , Jean-Pierre Majoral , Xiangyang Shi

Abstract Design of simple-component theranostic agents with enhanced tumor accumulation represents a novel strategy in the area of precision nanomedicine for effective tumor theranostics. Herein, we report an innovative theranostic strategy based on ultrasound-enhanced tumor accumulation of a theranostic agent of phosphorus dendrimer-copper(II) complexes (1G3-Cu). The employed 1G3-Cu complexes represent a drug-free nanotheranostic agent with a simple composition possessing an r1 relaxivity of 0.7024 mM−1 s−1 for T1-weighted magnetic resonance (MR) imaging and an IC50 of 1.24 μM to inhibit the growth of a pancreatic cancer cell line. We show that cancer cells can be inhibited by the 1G3-Cu complexes through the activation of the apoptotic process with the upregulation of Bax, P53 and PTEN, downregulation of Bcl-2, and decrease of intracellular ATP. With the assistance of ultrasound targeted microbubble destruction (UTMD) technology that can increase cell membrane permeability temporarily via sonoporation effect, the 1G3-Cu complexes enable enhanced tumor MR imaging and chemotherapy due to their improved tumor accumulation. With the proven minimal toxicity to normal tissues at imaging and therapeutic doses, the prepared 1G3-Cu complexes may be potentially employed for UTMD-enhanced theranostics of different types of cancer.

中文翻译:

基于磷树枝状聚合物的铜 (II) 配合物使超声增强肿瘤治疗诊断成为可能

摘要 设计具有增强肿瘤积累的简单组分治疗诊断剂代表了精确纳米医学领域有效肿瘤治疗诊断的新策略。在此,我们报告了一种创新的治疗诊断策略,该策略基于磷树枝状聚合物-铜 (II) 复合物 (1G3-Cu) 的治疗诊断剂的超声增强肿瘤积累。所采用的 1G3-Cu 复合物代表一种不含药物的纳米治疗剂,其组成简单,对 T1 加权磁共振 (MR) 成像具有 0.7024 mM-1 s-1 的 r1 弛豫率和 1.24 μM 的 IC50,以抑制胰腺癌细胞系。我们表明,癌细胞可以被 1G3-Cu 复合物通过激活细胞凋亡过程抑制,包括 Bax、P53 和 PTEN 的上调、Bcl-2 的下调和细胞内 ATP 的减少。在超声靶向微泡破坏 (UTMD) 技术的帮助下,该技术可以通过声孔效应暂时增加细胞膜通透性,1G3-Cu 复合物由于其改善了肿瘤积累而能够增强肿瘤 MR 成像和化疗。已证明在成像和治疗剂量下对正常组织的毒性最小,制备的 1G3-Cu 复合物可能用于不同类型癌症的 UTMD 增强治疗诊断。
更新日期:2020-08-01
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