含硫和氮掺杂荧光碳点（CDs）是介导癌细胞ROS产生的零维纳米颗粒，具有固有的抗癌特性。因此，它们被提议作为纳米诊疗工具，在成像引导癌症治疗中发挥作用。在这里，我们试图展示由CDs基纳米结构传递的西地那非对癌细胞（高表达PDE-5）的促进PDE-5介导的细胞死亡的正向强化通过过度表达参与ROS产生的基因。我们研究了叠氮-β-环糊精与CDs-炔烃之间的选择性Huisgen环加成反应，合成了均一的纳米结构，命名为CDs-PEG4-β-Cdx，由表面功能化的CDs与能够含有高量西地那非（> 20% w/w）等药物的β-环糊精组成，并以控制的方式释放。我们研究了CDs-PEG4-β-Cdx承载西地那非进入癌细胞，增强ROS产生并特异性地诱导细胞死亡，针对过表达PDE-5的癌细胞。这些纳米平台超越了EPR纳米医学的范畴，其中载体被认为是有毒药物的惰性载体。我们的发现促进了聪明的抗癌纳米平台的开发，将扰乱线粒体电子传递链（ROS产生）的纳米医药与PDE-5抑制剂结合起来，可以特异性地在癌细胞中触发氧化应激，而不考虑其位置。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Fluorescent sulfur- and nitrogen-doped carbon nanodots (CDs) are zero-dimensional nanoparticles that mediate ROS production in cancer cells, displaying inherent anticancer properties. Thus, they have been proposed as nanotheranostic tools useful in image-guided cancer therapy. Here, we try to show that cancerous cells (high PDE-5 expression) receiving sildenafil delivered by CDs-based nanostructures promote positive reinforcement of PDE-5-mediated cell death via the overexpression of genes involved in the production of ROS. We explored the regioselective Huisgen cycloaddition between azide-β-cyclodextrin and CDs-alkyne to synthetize homogeneous nanostructures, named CDs-PEG4-β-Cdx, consisting of CDs functionalized at the surface with β-cyclodextrins capable of including high amount drugs such as sildenafil (> 20 % w/w), and releasing them in a controlled manner. We investigated how CDs-PEG4-β-Cdx bearing sildenafil enter cells, enhancing ROS production and cell death specifically in cancer cells overexpressing PDE-5. These nanoplatforms go beyond the bounds of EPR-based nanomedicines in which carriers are conceived as inert vehicles of toxic drugs. Our findings enable the development of clever anticancer nanoplatforms that synergistically combine nanomedicines that perturb the mitochondrial electron transport chain (ROS production) with PDE-5 inhibitors which trigger oxidative stress specifically in cancer cells regardless of their location.Copyright © 2023 Elsevier B.V. All rights reserved.