Overcoming Hypoxia by Multistage Nanoparticle Delivery System to Inhibit Mitochondrial Respiration for Photodynamic Therapy,Advanced Functional Materials

当前位置： X-MOL 学术 › Adv. Funct. Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Overcoming Hypoxia by Multistage Nanoparticle Delivery System to Inhibit Mitochondrial Respiration for Photodynamic Therapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2019-02-08 , DOI: 10.1002/adfm.201807294
Donglin Xia _{1,

2} , Peipei Xu ₃ , Xingyu Luo ₁ , Jianfeng Zhu ₁ , Haiying Gu ₂ , Da Huo ₁ , Yong Hu _{1,

4}

Affiliation

Hypoxia, as characterized by the low local oxygen, confers on cancer cells resistance to oxygen‐consuming photodynamic therapy (PDT). The limited success reached by current approaches harnessing reoxygenation to enhance PDT outcome promotes the reconsideration of the design of the therapeutic approach. In this study, a multistage delivery system capable of reversing hypoxia is demonstrated. Unlike previous strategies that only expect to affect the peripheral tumor tissue, the size‐shrinkable system allows those deeply located hypoxia regions to be treated. Specifically, therapeutics, including atovaquone and indocyanine green derivatives that are respectively responsible for oxidative phosphorylation blockage and PDT, are encapsulated in a gelatin nanoparticle, whose structure would rupture to promote deep penetration when facing matrix metallopeptidase 2 enzyme overexpression in tumor tissue. The antihypoxic performance of the platform has been evaluated using a variety of analyses including flow‐cytometry assay, immunofluorescence, and micro‐positron‐emission tomography imaging. Tumor regression in animal models confirms the feasibility and effectiveness of conquering the PDT‐resistance through abrogating the oxygen consumption. It is hopeful that such a strategy could shed light on the development of next‐generation PDT‐adjuvant treatment.

中文翻译：

通过多阶段纳米颗粒输送系统克服缺氧抑制线粒体呼吸，从而进行光动力疗法。

以局部低氧为特征的缺氧赋予癌细胞对耗氧光动力疗法（PDT）的抗性。当前利用复氧来增强PDT结果的方法取得的成功有限，促使人们重新考虑治疗方法的设计。在这项研究中，证明了能够逆转缺氧的多阶段递送系统。与以前只希望影响周围肿瘤组织的策略不同，可缩小尺寸的系统允许治疗那些位于深处的缺氧区域。具体而言，将分别负责氧化磷酸化阻断和PDT的阿托伐醌和吲哚菁绿衍生物等治疗剂封装在明胶纳米颗粒中，当面对肿瘤组织中的基质金属肽酶2酶过度表达时，其结构会破裂以促进深层渗透。该平台的抗缺氧性能已通过各种分析进行了评估，包括流式细胞术，免疫荧光和微正电子发射断层扫描成像。动物模型中的肿瘤消退证实了通过消除耗氧量来克服PDT耐药性的可行性和有效性。希望这种策略可以为下一代PDT佐剂治疗的发展提供启发。动物模型中的肿瘤消退证实了通过消除耗氧量来克服PDT耐药性的可行性和有效性。希望这种策略可以为下一代PDT佐剂治疗的发展提供启发。动物模型中的肿瘤消退证实了通过消除耗氧量来克服PDT耐药性的可行性和有效性。希望这种策略可以为下一代PDT佐剂治疗的发展提供启发。

更新日期：2019-02-08

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南