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Updated: Jul 26, 2025
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Tailoring the Amphiphilic Structure of Zwitterionic AIE Photosensitizers to Boost Antitumor Immunity
Tianfu Zhang1,2, Xing Yang3, Xinwen Ou2
1School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 511436, China.
Abstract:
Although photodynamic therapy (PDT) for thorough cancer treatment is hindered by the limited generation of reactive oxygen species (ROS) with short lifetime from photosensitizers, PDT-induced antitumor immune response remedies the defects. Previous studies show that inducing immunogenic cell deaths is an attractive approach to activate antitumor immunity, which confers a robust adjuvanticity to dying cancer cells. In this work, amphiphilic luminogens with aggregation-induced emission characteristics (AIEgens) are rationally designed and synthesized. By modulating the hydrophobic π-bridge and zwitterionic functional groups, these AIEgens exhibit tunable organelle specificity to lysosome, endoplasmic reticulum, and plasma membrane and enhance ROS generation ability. Notably, the membrane-targeting AIEgen namely TPS-2 induces cell death and membrane rupture via PDT to facilitate the release of antigens and activation of immune cells. Furthermore, the size-controlled TPS-2 nanoaggregates are found to serve as an adjuvant, promoting antigen accumulation and delivery to sufficiently boost the in vivo antitumor immunity by only one dose injection in a prophylactic tumor vaccination model. This work thus provides new insights into optimizing AIE photosensitizers via a hydrophobicity-hydrophilicity balance strategy for evoking an antitumor immunity and directly suppressing the distanced tumor. A single small-molecular system for PDT-stimulated antitumor immunity is envisioned.
Insights
This study developed novel aggregation-induced emission materials (AIEgens) for photodynamic therapy (PDT) that enhance reactive oxygen species (ROS) generation. These AIEgens effectively target cancer cells, triggering an immune response to suppress tumors and boost immunity.
Area of Science:
- Biomedical Engineering
- Materials Science
- Immunology
Background:
- Photodynamic therapy (PDT) efficacy is limited by short-lived reactive oxygen species (ROS) generation.
- Activating antitumor immunity via immunogenic cell death is a promising strategy to overcome PDT limitations.
- Aggregation-induced emission materials (AIEgens) offer potential for enhanced photosensitization.
Purpose of the Study:
- To design and synthesize amphiphilic AIEgens with tunable organelle specificity and enhanced ROS generation for cancer therapy.
- To investigate the potential of AIEgens to induce immunogenic cell death and stimulate antitumor immunity.
- To evaluate the in vivo efficacy of AIEgen nanoaggregates as adjuvants for prophylactic tumor vaccination.
Main Methods:
- Rational design and synthesis of amphiphilic AIEgens by modulating hydrophobic π-bridge and zwitterionic groups.
- Tuning organelle specificity (lysosome, endoplasmic reticulum, plasma membrane) and ROS generation.
- In vitro evaluation of PDT-induced cell death and antigen release.
- In vivo assessment of AIEgen nanoaggregates in a prophylactic tumor vaccination model.
Main Results:
- Synthesized AIEgens demonstrated tunable organelle specificity and enhanced ROS generation.
- The membrane-targeting AIEgen (TPS-2) induced cell death and membrane rupture via PDT, facilitating antigen release and immune cell activation.
- Size-controlled TPS-2 nanoaggregates acted as effective adjuvants, boosting in vivo antitumor immunity with a single dose.
Conclusions:
- AIEgens can be optimized via a hydrophobicity-hydrophilicity balance for effective PDT and immune stimulation.
- A single small-molecule system holds promise for PDT-stimulated antitumor immunity and suppression of distant tumors.
- This approach provides new insights for developing AIE photosensitizers to evoke robust antitumor immune responses.
