GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy
GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy
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GE11-PDA-Pt@USPIOs纳米制剂缓解肿瘤缺氧和MRI/PAI引导肿瘤放化疗
DOI：
10.1039/c8bm01492b
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发表时间：
2019
影响因子：
6.6
通讯作者：
Zhang Chunfu
中科院分区：
文献类型：
--
作者：
Yang Chengcheng;Mi Xuan;Su Huilan;Yang Jingxing;Gu Yiyun;Zhang Lu;Sun Wenshe;Liang Xiaowen;Zhang Chunfu
放、化联合治疗对肿瘤具有协同治疗作用。然而，肿瘤微环境，例如缺氧和H2S水平升高，限制了其治疗效果。在这项研究中，我们开发了一种基于聚丙烯酸包覆的超小超顺磁性氧化铁纳米颗粒（PAA@USPIOs）的载顺铂、聚多巴胺包覆和GE 11肽缀合的多功能治疗诊断系统（GE 11-PDA-Pt@USPIOs），用于调节肿瘤缺氧微环境和磁共振成像/光声成像（MRI/派）引导的肿瘤放化疗。USPIO上的厚PAA涂层通过将PAA上的羧基与活化的顺铂络合而允许高效的顺铂负载。载药后的聚多巴胺（PDA）封装的后续薄层提供了进一步表面功能化的手段;它赋予颗粒光热性能，但不妨碍药物或铁离子的释放。GE 11-PDA-Pt@USPIOs对EGFR阳性肿瘤细胞具有高度特异性，能催化H2 O2分解为氧气，在体外低温条件下具有放化协同治疗作用。一旦静脉内给药，MRI和PA成像显示探针能够高效地在肿瘤中积累;这缓解了肿瘤缺氧条件，使肿瘤对放射治疗敏感。结果，放化联合治疗显著抑制了肿瘤生长。我们的研究首次说明USPIOs可以缓解肿瘤缺氧，并且GE 11-PDA-Pt@USPIOs对于EGFR阳性肿瘤的放化疗非常有效。
Radio-chemo combination therapy has synergetic therapeutic effects on tumors. However, the tumor microenvironment, e.g. hypoxia and elevated H2S levels, limits its treatment efficacy. In this study, we developed a cisplatin-loaded, poly dopamine-coated and GE11 peptide-conjugated multi-functional theranostic system (GE11-PDA-Pt@USPIOs) based on poly acrylic acid-coated ultra-small superparamagnetic iron oxide nanoparticles (PAA@USPIOs) for modulation of the tumor hypoxic microenvironment and magnetic resonance imaging/photoacoustic imaging (MRI/PAI) guided radio-chemotherapy of tumors. The thick PAA coating on the USPIOs allowed highly efficient cisplatin loading by complexing the carboxylic groups on PAA with activated cisplatin. A subsequent thin layer of polydopamine (PDA) encapsulation following drug loading provided a means of further surface functionalization; it endowed the particles with photo-thermal properties but did not impede release of the drug or iron ions. GE11-PDA-Pt@USPIOs had high specificity for EGFR-positive tumor cells, could catalyze decomposition of H2O2 to oxygen and exhibited radio-chemo synergetic therapeutic effects under hypothermia conditions in vitro. Once administered intravenously, MRI and PA imaging revealed that the probes were able to accumulate in tumors with high efficiency; this relieved the tumor hypoxic conditions, sensitizing the tumors to radiation therapy. As a result, radio-chemo combination therapy significantly inhibited tumor growth. Our study illustrates for the first time that USPIOs can relieve tumor hypoxia and that GE11-PDA-Pt@USPIOs are highly effective for radio-chemotherapy of EGFR-positive tumors.