Xu Lingxia, Meng Jiajia, Ren Mingming, Xu Yuping, Jiang Wentao, Zhao Wenbo, Zhou Min, Mao Chun, Zhang Shirong
National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University, Nanjing 210008, China.
J Colloid Interface Sci. 2025 Apr;683(Pt 2):484-495. doi: 10.1016/j.jcis.2024.12.163. Epub 2024 Dec 22.
Developing multimodal combination therapy strategies to disrupt the redox homeostasis within tumor cells is currently an important approach in cancer treatment. In this study, we designed and prepared multifunctional composite nanoparticles MPDA-PEG@MnO@2-DG (MPPMD NPs) utilizing mesoporous polydopamine nanoparticles (MPDA NPs) as carriers. These carriers were coated with polyethylene glycol (PEG), and manganese dioxide (MnO) and loaded with 2-deoxy-d-glucose (2-DG). Studies on mechanism revealed that upon accumulation in tumor cells via in situ injection, MnO can react with overexpressed HO to generate Mn, O, and toxic OH. Additionally, MnO undergoes an oxidation-reduction reaction (redox) with glutathione (GSH), consuming GSH and generating Mn. The resulting Mn further participates in Fenton-like reactions with overexpressed HO within the tumor. Furthermore, under 808 nm laser, MPPMD NPs facilitate photothermal therapy (PTT), promoting the generation of reactive oxygen species (ROS), inducing oxidative stress, and reducing the adenosine triphosphate (ATP) level. Concurrently, the 2-DG loaded by MPPMD NPs disguised as glucose disrupts the glycolysis process, inhibiting ATP production, and effectively inducing tumor starvation therapy (ST). By leveraging the multifunctionality of MPPMD NPs, this work realized the disruption of redox homeostasis within tumor cells, providing potential strategies for multimodal tumor treatment.
开发多模态联合治疗策略以破坏肿瘤细胞内的氧化还原稳态是目前癌症治疗中的一种重要方法。在本研究中，我们以介孔聚多巴胺纳米颗粒（MPDA NPs）为载体，设计并制备了多功能复合纳米颗粒MPDA-PEG@MnO@2-DG（MPPMD NPs）。这些载体涂覆有聚乙二醇（PEG），并负载二氧化锰（MnO）和2-脱氧-D-葡萄糖（2-DG）。机制研究表明，通过原位注射在肿瘤细胞中积累后，MnO可与过表达的HO反应生成Mn、O和有毒的OH。此外，MnO与谷胱甘肽（GSH）发生氧化还原反应，消耗GSH并生成Mn。生成的Mn进一步参与肿瘤内与过表达的HO的类芬顿反应。此外，在808 nm激光照射下，MPPMD NPs促进光热疗法（PTT），促进活性氧（ROS）的生成，诱导氧化应激，并降低三磷酸腺苷（ATP）水平。同时，MPPMD NPs负载的2-DG伪装成葡萄糖破坏糖酵解过程，抑制ATP生成，并有效诱导肿瘤饥饿疗法（ST）。通过利用MPPMD NPs的多功能性，这项工作实现了肿瘤细胞内氧化还原稳态的破坏，为多模态肿瘤治疗提供了潜在策略。
