Department of Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Biomater Sci. 2023 Nov 7;11(22):7387-7396. doi: 10.1039/d3bm01198d.
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 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 Tc. 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 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 , as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with Tc) tumor imaging . 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.
具有放大的被动肿瘤靶向和增强的蛋白质抗性的纳米平台可以避免被网状内皮系统不必要地摄取，并实现高肿瘤保留，以实现准确的肿瘤治疗。为了实现这一目标，我们构建了具有芳香骨架核心的磷核壳结构树状大分子（CSTDs）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）双模成像。在这项研究中，部分磷 P-G2.5/G3 CSTDs（G 表示代）与四氮杂环十二烷四乙酸（DOTA）、Cy5.5 和 1,3-丙烷磺酸（1,3-PS）缀合，然后用 Tc 标记。形成的 P-G2.5/G3-DOTA-Cy5.5-PS CSTDs 具有良好的单分散性，粒径为 10.1nm，具有所需的蛋白质抗性和细胞相容性。引人注目的是，与核心和壳成分均为聚（酰胺胺）树状大分子的对照材料 G3/G3-DOTA-Cy5.5-PS 相比，开发的 P-G2.5/G3-DOTA-Cy5.5-PS 配合物允许更有效的细胞摄取和在 3D 肿瘤球体中更显著的渗透，以及更显著的肿瘤保留和积累，以增强荧光和 SPECT（用 Tc 标记后）肿瘤成像。我们的研究表明，所构建的 CSTDs 的核心刚性对于放大肿瘤增强的渗透性保留（EPR）效应以改善癌症纳米医学的发展具有重要意义。
