Hemoglobin-mediated biomimetic synthesis of paramagnetic O(2)-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor.
Hemoglobin-mediated biomimetic synthesis of paramagnetic O(2)-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor.
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血红蛋白介导的顺磁 O(2) 演化治疗诊断纳米探针的仿生合成，用于 MR 成像引导的肿瘤增强光动力治疗
DOI：
10.7150/thno.46228
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发表时间：
2020
期刊：
影响因子：
12.4
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Shi X;Yang W;Ma Q;Lu Y;Xu Y;Bian K;Liu F;Shi C;Wang H;Shi Y;Zhang B
实体肿瘤的缺氧微环境严重限制了光动力治疗（PDT）的疗效。因此，开发光敏剂与氧共载的纳米载体，同时具备成像引导能力，在癌症治疗中具有重要意义。然而，先前报道的这些多功能探针的合成方法复杂，并且使用的原料有毒。方法：利用人内源性蛋白血红蛋白（Hb）同时仿生合成基于gd的纳米结构，并共负载氯e6 （Ce6）和氧，缓解肿瘤的缺氧环境，实现磁共振成像（MRI）引导下的增强PDT。Gd@HbCe6-PEG纳米探针是通过绿色和蛋白质仿生方法合成的。通过静脉注射Gd@HbCe6-PEG对荷瘤小鼠体外和体内的物理化学性质，包括松驰度、携氧/释放能力和PDT效果。形态学和功能MRI评估PDT的疗效。结果：成功合成了具有多种功能的致密Gd@HbCe6-PEG纳米结构。在纳米粒子治疗后，嵌入的MR片段在照亮肿瘤病变和指导治疗方面是有效的。通过光谱分析和体外氧检测仪证实了仿生合成Hb的携氧能力。此外，通过光声成像和免疫荧光染色验证了静脉注射Gd@HbCe6-PEG后体内肿瘤氧合对缓解肿瘤缺氧的作用。通过形态学和功能磁共振成像观察PDT对早期病变的有效治疗效果。重要的是，治疗后观察到颗粒的肾脏快速清除。结论：本研究以人内源性蛋白为原料，实现了多功能纳米探针的仿生合成，可同时用于肿瘤氧合和成像引导下的PDT增强。PDT后6 h通过弥散加权成像（DWI）定量证实治疗效果。
The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic. Methods: Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@HbCe6-PEG nanoprobes were synthesized via a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@HbCe6-PEG, were measured in vitro and in vivo on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT. Results: The results demonstrated the successful synthesis of compact Gd@HbCe6-PEG nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector in vitro. Further, tumor oxygenation for alleviating tumor hypoxia in vivo after intravenous injection of Gd@HbCe6-PEG was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment. Conclusion: In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).
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