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Updated: May 17, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Supramolecular Assembly of Stepped-Persistent ROS Nanogenerator for Sustained Tumor Immunotherapy
Zhenqiang Wang1, Ming Qin1, Wenjing Lai1
1Department of Pharmacy, The Second Affiliated Hospital, Third Military Medical University (Army Medical University), No. 83 Xinqiao Road, Chongqing, China.
Abstract:
ROS-based tumor elimination could trigger systemic antitumor immune responses. However, these strategies are fundamentally restricted by insufficient ROS generation and uncontrollable kinetic processes. Besides, tumor-associated macrophages often reverted to an immunosuppressive phenotype due to a lack of sustained stimulation. To achieve both effective tumor eradication and sustained activation of tumor immune microenvironment, a stepped-persistent ROS nanogenerator supramolecularly assembled multiple ROS generation modules was synthesized. G-quadruplexes (G4s)-DNA nanochains, functionalized with Hemin and Ce6, served as a structure-directing agent for synthesizing polydopamine nanofibers (PDANFs). Semiquinone radicals generated during dopamine polymerization were stabilized by supramolecular interaction between G4s and polydopamine oligomers. Under NIR irradiation, PDANFs could explosively produce singlet oxygen (1O2). Moreover, the nanoconfined catalytic cascade reaction between semiquinone radicals and G4s/hemin DNAzyme leads to a dissipative generation of hydroxyl radical (•OH), extending ROS generation after NIR irradiation above an effective cytotoxic level for adequate tumor inhibition and immune activation. Additionally, PDANFs also catalyzed pathological H2O2 to generate sub-cytotoxic •OH, sustaining the antitumor phenotype of macrophage. The nanogenerators showed a slow reduction of ROS levels and remained above 47% and 23% after 1 and 48 h of photoactivation. Thereby, effective tumor inhibition and sustained immunoactivation were achieved. This system significantly advances ROS regulators for tumor immunotherapy.
Insights
This study introduces a novel nanogenerator that produces reactive oxygen species (ROS) in a sustained manner for enhanced tumor elimination and immune activation. The nanogenerator effectively inhibits tumors and promotes long-lasting antitumor immunity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunotherapy
Background:
- Reactive oxygen species (ROS) hold promise for tumor elimination and triggering systemic antitumor immune responses.
- Current ROS-based strategies face limitations due to insufficient ROS generation and uncontrolled kinetics.
- Tumor-associated macrophages often adopt an immunosuppressive phenotype, hindering effective immunotherapy.
Purpose of the Study:
- To develop a stepped-persistent ROS nanogenerator for effective tumor eradication and sustained activation of the tumor immune microenvironment.
- To overcome the limitations of insufficient ROS generation and uncontrollable kinetics in current strategies.
- To sustain the antitumor phenotype of macrophages for enhanced immunotherapy.
Main Methods:
- Synthesized polydopamine nanofibers (PDANFs) using G-quadruplexes (G4s)-DNA nanochains functionalized with Hemin and Ce6 as a structure-directing agent.
- Utilized supramolecular interactions between G4s and polydopamine oligomers to stabilize semiquinone radicals.
- Investigated the synergistic ROS generation of singlet oxygen (¹O₂) and hydroxyl radical (•OH) under near-infrared (NIR) irradiation and subsequent catalytic reactions.
Main Results:
- The synthesized nanogenerators demonstrated explosive ¹O₂ production under NIR irradiation and sustained •OH generation via a catalytic cascade reaction.
- PDANFs effectively catalyzed endogenous H₂O₂ to generate sub-cytotoxic •OH, maintaining macrophage antitumor phenotypes.
- ROS levels remained significantly elevated (above 47% at 1h and 23% at 48h post-activation), indicating persistent ROS generation.
Conclusions:
- The developed stepped-persistent ROS nanogenerator achieved effective tumor inhibition and sustained immunoactivation.
- This system represents a significant advancement in ROS regulators for tumor immunotherapy.
- The sustained ROS generation and macrophage phenotype modulation offer a promising strategy for cancer treatment.
