Integrated energy conversion units in nanoscale frameworks induce sustained generation and amplified lethality of singlet oxygen in oxidative therapy of tumor
Jing Zhu,
Tao Ding,
Kaifei Jin,
Yuxin Xing,
Jixi Huang,
Daqing Xia,
Kaiyong Cai,
Jixi Zhang
Affiliations
Jing Zhu
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Tao Ding
Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Kaifei Jin
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Yuxin Xing
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Jixi Huang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Daqing Xia
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Kaiyong Cai
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Jixi Zhang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University Chongqing China
Abstract Reactive oxygen species (ROS) driven endoplasmic reticulum (ER) stress is highly promising for tumor therapy but restrained by the nondurable introduction and limited lifetime of oxidative species. Here, a therapeutic nanosystem with sustainable ROS generation ability was developed by accommodating luminol derivatives (L012) in hyaluronic acid‐modified metal‐organic frameworks of Fe3+ and porphyrin ligand (TCPP). After particle accumulation in the tumor, ∙OH radicals from Fe3+ sites catalyzed conversion of H2O2 can react with confined L012 transducers to generate chemiluminescence (CL). Because of the distance constraints, the CL energy was significantly extracted (96%) by adjacent TCPP and further activate oxygen to long‐lifetime singlet oxygen (1O2), whose yield can be further boosted by the catalase‐like activity of the frameworks. By regulating the substrate consumption through energy conversion, the cascade process resulted in increased ROS levels (2.4‐fold) and sustainable oxidation (24 h), which induced continuously accumulated ER stress, high autophagic levels, and amplified lethality against the tumor. This work opens a new avenue to explore reticular nanostructures with complementarily arranged and synergistically spaced conversion units in advancing ROS therapy.
