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首页> 外文期刊>Acta biomaterialia >Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform
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Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform

机译：基于硫化铜的硫化铜局部药物递送系统作为有效的癌症协同治疗和治疗平台

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Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment.
机译：用联合治疗的局部癌症治疗引起了有效抑制肿瘤生长的越来越关注。在这项工作中，我们引入了扩散分子保留（DMR）肿瘤靶向效果，采用转铁蛋白（TF）修饰的中空介孔CUS纳米颗粒（HMCU NPS）通过突出性（PT）之后的肿瘤保留进行广泛漫射的新策略注射。这里，具有强近红外线（NIR）吸收和光热转化效率的HMCU NP可以不仅可以不仅发起药物载体，而且可以不仅是药物载体，而且是用于引导化学光疗法的光声成像的强烈造影剂。使用对肿瘤细胞具有深远细胞毒性的铁依赖性矮子（AS）作为模型药物。结果，如上所加载的TF-HMCU（AS / TF-HMCUS NPS）系统可以特别地靶向肿瘤细胞，并同步地递送为肿瘤进入肿瘤以实现增强的抗肿瘤活性。结果发现，通过TF介导的内吞作用，通过MCF-7细胞占用/ TF-HMCUS NPS，并且可以有效地将NIR光转化为光热疗法的热量，以及为光动力产生的高水平的活性氧物质（ROS）治疗。此外，在体内抗肿瘤效力研究表明，在NIR激光照射下通过Peritumoral（Pt）注射用AS / TF-HMCU NPS处理的肿瘤鼠标呈现出约74.8％的最强抑制率，即使给药频率降低。此外，为了演示DMR，采用PT注射后的光学成像，光声断层扫描和免疫荧光，以跟踪体内AS / TF-HMCUS NPS的行为。结果表明，TF-HMCUS NPS延长了局部积累和保留以及缓慢的血管摄取和广泛的间质扩散，这与AS / TF-HMCUS NPS的生物分布研究一致。因此，通过DMR局部递送的方法与多机制疗法合并可能是癌症治疗的有希望的方法。

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