Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy

Chen, Ying‐Chi; Li, Yiting; Lee, Chin‐Lai; Kuo, Ying Hwa; Ho, Chia-Lun; Lin, Wei-Che; Hsu, Ming‐Hsi; Long, Xizi; Chen, J. M.; Li, Wei Peng; Su, Chia‐Hao; Okamoto, Akimitsu; Yeh, Chen-Sheng

doi:10.1038/s41565-023-01476-2

Cited by 13 publications

(4 citation statements)

References 28 publications

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“…Preparation, characterization, and optimization of functionalized liposomes DSPE-PEG has been recently employed to modify immunoglobulin and CpG-DNA/peptide on the cell surface based on its lipid raft-like structure [5,30] and showed that C18 diacyllipid meets the optimum requirements for cell membrane modification. [30,31] To avoid lymph node targeting mediated by albumin binding to the lipid tail [31] and achieve effective membrane fusion in vivo, [32] we integrated DSPE-PEG into liposomes according to the previous literature. [2] Since DSPE-PEG acts as both a tumor-targeting and membrane-anchoring ligand in liposomes, the MW effect of PEG is optimized to distinguish these two functions.…”

Section: Resultsmentioning

confidence: 99%

A High‐Efficiency Bioorthogonal Tumor‐Membrane Reactor for In Situ Selective and Sustained Prodrug Activation

Ma,

Zhou,

Long

et al. 2024

Angew Chem Int Ed

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The site‐specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor‐targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a “drug factory” that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene‐caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.

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Section: Resultsmentioning

confidence: 99%

A High‐Efficiency Bioorthogonal Tumor‐Membrane Reactor for In Situ Selective and Sustained Prodrug Activation

Ma,

Zhou,

Long

et al. 2024

Angew Chem Int Ed

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“…With due consideration given to the fact that TADI-COF has a stronger X-ray absorption capacity than UiO-66(Hf), the radiolytic effect exerted by TADI-COF on water under 6 MV X-ray radiation was investigated (Figure A). Specifically, exposure of TADI-COF (1.0 mg/mL), supplemented with dihydroethidium (DHE), to X-ray radiation (10 Gy) resulted in a significant enhancement of fluorescence at 620 nm due to the oxidation of DHE to ethidium ions by radiolytically generated ·O 2 – ; the resulting fluorescence intensity being 4.2 times greater than that of the radiated DHE solution (Figures B and S6). By contrast, no detectable change in fluorescence was observed in the absence of X-ray radiation.…”

Section: Results and Discussionmentioning

confidence: 99%

A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

Zhou,

Guan,

Zhou

et al. 2023

ACS Nano

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Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis of an iodineand ferrocene-loaded covalent organic framework (COF) nanozyme, termed TADI-COF-Fc, for the enhancement of radiotherapeutic efficacy in the treatment of radioresistant esophageal cancer. The iodine atoms on the COF framework not only exerted a direct effect on radiotherapy, increasing its efficacy by increasing X-ray absorption, but also promoted the radiolysis of water, which increased the production of reactive oxygen species (ROS). In addition, the ferrocene surface decoration disrupted redox homeostasis by increasing the levels of hydroxyl and lipid peroxide radicals and depleting intracellular antioxidants. Both in vitro and in vivo experiments substantiated the excellent radiotherapeutic response of TADI-COF-Fc. This study demonstrates the potential of COF-based multinanozymes as radiosensitizers and suggests a possible treatment integration strategy for combination oncotherapy.

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“…5−11 RDT capitalizes on the phenomenon of radiocatalysis, which generates additional reactive oxygen in addition to the ionization effects induced by radiation, thereby enhancing the overall anticancer effects. 12,13 However, the efficacy of RDT is contingent upon the presence of oxygen, which poses limitations in hypoxic tumor environments. 5,14 To address this challenge, here, the concept of radiationboosted chemodynamic therapy was proposed as a potential solution.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In recent years, radiodynamic therapy (RDT) has emerged as a promising avenue for inducing durable anticancer immune responses. − RDT capitalizes on the phenomenon of radiocatalysis, which generates additional reactive oxygen in addition to the ionization effects induced by radiation, thereby enhancing the overall anticancer effects. , However, the efficacy of RDT is contingent upon the presence of oxygen, which poses limitations in hypoxic tumor environments. , …”

Section: Introductionmentioning

confidence: 99%

Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response

Chen,

Deng,

et al. 2024

ACS Appl. Mater. Interfaces

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Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a “super” tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

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Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy

Cited by 13 publications

References 28 publications

A High‐Efficiency Bioorthogonal Tumor‐Membrane Reactor for In Situ Selective and Sustained Prodrug Activation

A High‐Efficiency Bioorthogonal Tumor‐Membrane Reactor for In Situ Selective and Sustained Prodrug Activation

A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response

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