Redox Imbalance Triggered Intratumoral Cascade Reaction for Tumor "turn on" Imaging and Synergistic Therapy. Issue 16 (22nd January 2023)

• Record Type: Journal Article
• Authors: Liu, Juanzu; Zhu, Han; Lin, Leping; Zhao, Wei; Zhu, Xiaobo; Pang, Dai‐Wen; Liu, An‐An
• Is Part Of: Small. Volume 19:Issue 16(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-22
• Subjects: cascade reaction -- multifunctional integrated nanospheres -- redox imbalance -- synergistic therapy -- "turn on" fluorescence/magnetic resonance imaging; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202206272
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: The redox homeostasis in tumors enhances their antioxidant defense ability, limiting reactive oxygen species mediated tumor therapy efficacy. The development of strategies for specific and continuous disruption of the redox homeostasis in tumor cells facilitates the improvement of the cancer therapeutic effect by promoting the apoptosis of tumor cells. Herein, a responsively biodegradable targeting multifunctional integrated nanosphere (HDMn‐QDs/PEG‐FA) is designed to enhance the anti‐tumor efficacy by triggering intratumoral cascade reactions to effectively disrupt intracellular redox homeostasis. Once HDMn‐QDs/PEG‐FA enters tumor cells, manganese dioxide (MnO2 ) shell on the surface of nanosphere consumes glutathione (GSH) to produce Mn 2+, enabling enhanced chemodynamic therapy (CDT) via a Fenton‐like reaction and T1 ‐weighted magnetic resonance imaging. Meanwhile, the degradation of MnO2 can also cause the fluorescence recovery of quantum dots conjugated on the surface of the shell, realizing "turn‐on" fluorescence imaging. In addition, the doxorubicin is released because of the cleavage of the embedded SS bond in the hybrid core framework by GSH. A superior synergistic therapeutic efficiency combined CDT and chemotherapy is shown by HDMn‐QDs/PEG‐FA in vivo. The tumor‐inhibition rate reaches to 94.8% and does not cause normal tissue damage due to the good targeting and tumor microenvironment‐specific response. Abstract : A responsively biodegradable multifunctional integrated nanosphere (HDMn‐QDs/PEG‐FA) is constructed to enhance the anti‐tumor efficacy by triggering intratumoral cascade reactions disrupting intracellular redox homeostasis. Meanwhile, using the multifunctional integrated nanosphere, the asynchronous "turn‐on" fluorescence and magnetic resonance imaging are achieved for pinpointing the tumor site and long‐term imaging.