纳米材料独特的性质使其具有固有的酶样特性，与天然酶相比具有独特的优势。碳点（CDs）是一种重要的量子尺寸的纳米材料，具有巨大的生物成像、药物载体和纳米系统应用潜力。碳点具有谷胱甘肽（GSH）氧化酶或过氧化物酶的固有酶样性质。本研究探讨了一种可以同时携带siRNA和多柔比星（DOX）的共递送纳米系统。基于碳点的共递送系统被表面修饰了聚乙烯亚胺（PEI），并将siMRP1与化疗药物荷载在表面上，具有酸触发的药物释放。碳点-PEI是通过一步微波辅助方法合成的，PEI是原材料和反应过程中的缓冲剂，使碳点表现出优异的光学特性。CD-PEI可以将siMRP1和DOX载入瘤内，并在细胞中以酸触发方式同步释放。这些颗粒展现出GSH氧化酶样催化性质，将GSH氧化为氧化型谷胱甘肽，同时增加活性氧（ROS）的含量。我们发现，共递送系统通过抑制MRP1的沉默，增加DOX的积累并显著增强由CD-PEI-DOX诱导的细胞活性抑制效应，对抗化疗药物的耐药性。共递送系统极大地抑制了移植瘤模型中的肿瘤生长，并通过siRNA介导的MRP1敲除来对抗MRP1的功能。综上所述，我们揭示了碳点配合siRNA和化疗药物在抑制MRP1和GSH氧化方面，克服肺癌化疗耐药的潜在作用。我们的发现意味着碳点有望在肺癌治疗的临床实践中对抗化疗耐药，提高多柔比星的治疗效果。 © 2023 Yu等。

Nanomaterials exhibited intrinsic enzyme-like properties due to the unique properties compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. Carbon dots possess intrinsic enzyme-like properties, such as glutathione (GSH) oxidase or peroxidase activities.A co-delivery nanosystem that could carry siRNA and doxorubucin (DOX) simultaneously has been studied in this work. The co-delivery based on carbon dots was surface-modified with poly-ethylenimine (PEI) and loaded the siMRP1 with chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI was raw materials and passivator during the reaction process that makes CDs exhibit excellent optical property.The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumors and releasing them synchronously in cells in an acid-triggered manner. The particles exhibited GSH oxidase-like catalytic property, oxidizing GSH to oxidized glutathione with concomitant increase of reactive oxygen species (ROS). We found that silencing of MRP1 by co-delivery system antagonized chemoresistance by increasing DOX accumulation and significantly enhancing the inhibitory effect of cell viability induced by CD-PEI-DOX. The co-delivery system dramatically inhibited tumor growth in xenograft model, and CDs counteracted MRP1 function by siRNA-mediated knockdown of MRP1.Taken together, we uncover the potential role of CDs with a combination of siRNA and chemotherapeutics in overcoming chemoresistance of lung cancer by suppressing MRP1 and oxidation of GSH. Our findings imply its potential of antagonizing chemoresistance to enhance therapeutic efficiency of doxorubicin in clinical practices of lung cancer treatment.© 2023 Yu et al.