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.
Department of Chemistry, College of Natural and Computational Sciences, University of Gondar, 196, Gondar, Ethiopia.
J Mater Chem B. 2024 Oct 2;12(38):9524-9532. doi: 10.1039/d4tb01747a.
The design of efficient multifunctional nanomedicines to overcome adverse side effects within biological systems and to achieve desirable computed tomography (CT) imaging and therapeutics of tumors remains challenging. Herein, we report the design of multifunctional nanoclusters (NCs) based on generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers. In brief, G3 dendrimers were crosslinked with 4,4'-dithiodibutryic acid (DA) to generate disulfide-bond-containing dendrimer nanoclusters (DNCs), functionalized with 1,3-propane sultone (1,3-PS) to be zwitterionic, loaded with gold nanoparticles (Au NPs), and finally encapsulated with the drug doxorubicin (DOX). The designed DOX/Au@DNCs-PS possess a favorable colloidal stability with a hydrodynamic size of 249.4 nm, a redox-responsive drug release profile, and enhanced cellular uptake . We show that DOX/Au@DNCs-PS have a greater DOX penetration and growth inhibition of three-dimensional (3D) tumor spheroids than the single dendrimer counterpart in vitro. Furthermore, the developed Au@DNCs-PS enable a better Au-mediated X-ray attenuation property than the single dendrimer counterpart material. Likely due to the amplified enhanced permeability and retention (EPR) effect, the created Au@DNCs-PS and DOX/Au@DNCs-PS enable better CT imaging and chemotherapeutic effect of a mouse breast tumor model, respectively, than the single dendrimer counterparts. With its proven biocompatibility, the constructed formulation may hold promising potential for development for different cancer nanomedicine applications.
设计高效多功能纳米药物以克服生物系统中的不良反应，并实现肿瘤理想的计算机断层扫描（CT）成像和治疗仍然具有挑战性。在此，我们报告了基于第三代（G3）聚酰胺-胺（PAMAM）树枝状大分子的多功能纳米团簇（NCs）的设计。简而言之，G3 树枝状大分子与 4,4'-二硫代二丁酸（DA）交联，生成含二硫键的树枝状大分子纳米团簇（DNCs），用 1,3-丙烷磺内酯（1,3-PS）功能化，使其带负电荷，负载金纳米粒子（Au NPs），最后包裹药物阿霉素（DOX）。设计的 DOX/Au@DNCs-PS 具有良好的胶体稳定性，水动力粒径为 249.4nm，具有氧化还原响应性药物释放特性和增强的细胞摄取。我们表明，DOX/Au@DNCs-PS 在体外比单树突大分子对照物具有更大的 DOX 渗透和对三维（3D）肿瘤球体的生长抑制作用。此外，开发的 Au@DNCs-PS 比单树突大分子对照材料具有更好的 Au 介导的 X 射线衰减特性。可能由于放大的增强通透性和保留（EPR）效应，所创建的 Au@DNCs-PS 和 DOX/Au@DNCs-PS 分别比单树突大分子对照物能够更好地进行 CT 成像和化疗治疗小鼠乳腺癌模型。由于其已证明的生物相容性，所构建的制剂可能具有很大的潜力，可用于不同的癌症纳米医学应用。
