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Phosphorus core–shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters
Biomaterials Science ( IF 5.8 ) Pub Date : 2023-09-22 , DOI: 10.1039/d3bm01198d Mengsi Zhan 1, 2 , Dayuan Wang 2 , Lingzhou Zhao 3 , Liang Chen 2 , Zhijun Ouyang 2 , Serge Mignani 4 , Jean-Pierre Majoral 5, 6 , Jinhua Zhao 3 , Guixiang Zhang 1 , Xiangyang Shi 2, 4 , Mingwu Shen 2
Biomaterials Science ( IF 5.8 ) Pub Date : 2023-09-22 , DOI: 10.1039/d3bm01198d Mengsi Zhan 1, 2 , Dayuan Wang 2 , Lingzhou Zhao 3 , Liang Chen 2 , Zhijun Ouyang 2 , Serge Mignani 4 , Jean-Pierre Majoral 5, 6 , Jinhua Zhao 3 , Guixiang Zhang 1 , Xiangyang Shi 2, 4 , Mingwu Shen 2
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Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core–shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with 99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with 99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.
中文翻译：
用于增强肿瘤成像的磷核壳结构树状聚合物：主链的刚性很重要
具有放大的被动肿瘤靶向性和增强的蛋白质耐受性的纳米平台可以避免网状内皮系统不必要的摄取，并实现高肿瘤保留，以实现准确的肿瘤治疗诊断。为了实现这一目标，我们构建了具有刚性芳香主链核心的磷核壳结构树状聚合物（CSTD）作为纳米平台，用于增强肿瘤的荧光和单光子发射计算机断层扫描（SPECT）双模式成像。在本研究中，磷P-G2.5/G3 CSTD（G表示代）与四氮杂环十二烷四乙酸（DOTA）、花青5.5（Cy5.5）和1,3-丙磺酸盐（1,3- PS），然后用99m Tc 标记。形成的P-G2.5/G3-DOTA-Cy5.5-PS CSTD具有良好的单分散性，粒径为10.1 nm，并具有所需的蛋白质耐受性和细胞相容性。引人注目的是，与核和壳成分均为软聚酰胺胺树枝状聚合物的对应材料G3/G3-DOTA-Cy5.5-PS相比，开发的P-G2.5/G3-DOTA-Cy5.5-PS复合物可以在体外实现更有效的细胞摄取和更显着的 3 维肿瘤球体渗透，以及更显着的肿瘤保留和积累，以增强双模式荧光和 SPECT（用99m Tc 标记后）体内肿瘤成像。我们的研究表明，所构建的 CSTD 核心的刚性对于放大肿瘤增强通透性保留 (EPR) 效应至关重要，从而改善癌症纳米药物的开发。
更新日期：2023-09-22
中文翻译：
用于增强肿瘤成像的磷核壳结构树状聚合物：主链的刚性很重要
具有放大的被动肿瘤靶向性和增强的蛋白质耐受性的纳米平台可以避免网状内皮系统不必要的摄取，并实现高肿瘤保留，以实现准确的肿瘤治疗诊断。为了实现这一目标，我们构建了具有刚性芳香主链核心的磷核壳结构树状聚合物（CSTD）作为纳米平台，用于增强肿瘤的荧光和单光子发射计算机断层扫描（SPECT）双模式成像。在本研究中，磷P-G2.5/G3 CSTD（G表示代）与四氮杂环十二烷四乙酸（DOTA）、花青5.5（Cy5.5）和1,3-丙磺酸盐（1,3- PS），然后用99m Tc 标记。形成的P-G2.5/G3-DOTA-Cy5.5-PS CSTD具有良好的单分散性，粒径为10.1 nm，并具有所需的蛋白质耐受性和细胞相容性。引人注目的是，与核和壳成分均为软聚酰胺胺树枝状聚合物的对应材料G3/G3-DOTA-Cy5.5-PS相比，开发的P-G2.5/G3-DOTA-Cy5.5-PS复合物可以在体外实现更有效的细胞摄取和更显着的 3 维肿瘤球体渗透，以及更显着的肿瘤保留和积累，以增强双模式荧光和 SPECT（用99m Tc 标记后）体内肿瘤成像。我们的研究表明，所构建的 CSTD 核心的刚性对于放大肿瘤增强通透性保留 (EPR) 效应至关重要，从而改善癌症纳米药物的开发。
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