Persistent Regulation of Tumor Hypoxia Microenvironment via a Bioinspired Pt‐Based Oxygen Nanogenerator for Multimodal Imaging‐Guided Synergistic Phototherapy,Advanced Science

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Persistent Regulation of Tumor Hypoxia Microenvironment via a Bioinspired Pt‐Based Oxygen Nanogenerator for Multimodal Imaging‐Guided Synergistic Phototherapy
Advanced Science ( IF 14.3 ) Pub Date : 2020-07-29 , DOI: 10.1002/advs.201903341
Qing You _{1,

2} , Kaiyue Zhang _{2,

3} , Jingyi Liu _{1,

2} , Changliang Liu _{1,

2} , Huayi Wang _{1,

4} , Mengting Wang _{1,

2} , Siyuan Ye _{1,

4} , Houqian Gao _{1,

2} , Letian Lv _{1,

2} , Chen Wang _{1,

2} , Ling Zhu ₁ , Yanlian Yang _{1,

2}

Affiliation

Multifunctional nanoplatforms for imaging‐guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre‐existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O₂ self‐enriched nanoplatform is constructed for multimodal imaging‐guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one‐step method using platinum (Pt) nanozyme‐decorated metal–organic frameworks (MOF) as the inner template. The Pt‐decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin‐chelated gadolinium (HSA‐Gd, HGd) and loaded with indocyanine green (ICG) (ICG‐PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X‐ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt‐decorated nanoplatform endows remarkable catalase‐like behavior and facilitates the continuous decomposition of the endogenous H₂O₂ into O₂ to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor‐targeting ability of the nanocomposites. This TME‐responsive and O₂ self‐supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging‐guided synergistic phototherapy of solid tumors.

中文翻译：

通过仿生铂基氧气纳米发生器持续调节肿瘤缺氧微环境，用于多模态成像引导协同光疗

用于成像引导协同抗肿瘤治疗的多功能纳米平台在生物医学应用中非常受欢迎。然而，抗癌治疗在很大程度上受到预先存在的缺氧肿瘤微环境（TME）的影响，这不仅导致肿瘤对光动力疗法（PDT）产生抵抗，而且促进肿瘤的发生和进展。在这里，构建了一个基于八面体金纳米壳（GNS）的连续O ₂自富集纳米平台，用于多模态成像引导的协同光疗，八面体金纳米壳是使用铂（Pt）纳米酶装饰的金属通过更简便和直接的一步法构建的–有机框架（MOF）作为内部模板。 Pt修饰的MOF@GNSs（PtMGs）进一步用人血清白蛋白螯合钆（HSA-Gd，HGd）进行功能化，并负载吲哚青绿（ICG）（ICG-PtMGs@HGd）以实现协同PDT/PTT效果和荧光（FL）/多光谱光声断层扫描（MSOT）/X射线计算机断层扫描（CT）/磁共振（MR）成像。 Pt修饰的纳米平台具有显着的过氧化氢酶样行为，有助于内源性H ₂ O ₂持续分解为O ₂ ，从而增强低氧TME下的PDT效果。 HSA修饰增强了纳米复合材料的生物相容性和肿瘤靶向能力。这种 TME 响应和 O ₂自补充纳米颗粒作为多功能治疗诊断纳米平台具有巨大的潜力，可用于实体瘤的多模态成像引导协同光疗。

更新日期：2020-09-10

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