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Selective Cell Elimination from Mixed 3D Culture Using a Near Infrared Photoimmunotherapy Technique
Published on: March 14, 2016
An Active Self-Mitochondria-Targeting Cyanine Immunomodulator for Near-Infrared II Fluorescence Imaging-Guided
Jin-Feng Yu1, Yu Wen1,2, Ming Li1
1School of Materials Science and Engineering, Central South University, Changsha, Hunan, 410083, China.
Abstract:
Photodynamic therapy targeting mitochondria represents a promising therapeutic strategy for fighting diverse types of cancers. However, the currently available photosensitizers (PSs) suffer from insufficient therapeutic potency, limited mitochondria delivery efficiency, and the inability to treat invisible metastatic distal cancers. Herein, an active self-mitochondria-targeting heptapeptide cyanine (HCy) immunomodulator (I2HCy-QAP) is reported for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic immunotherapy of primary and distal metastatic cancers. The I2HCy-QAP is designed by introducing a quaternary ammonium salt with a phenethylamine skeleton (QAP) into the iodinated HCy photosensitizer. The I2HCy-QAP can precisely target mitochondria due to the lipophilic cationic QAP unit, present strong NIR-II fluorescence tail emission, and effectively generate singlet oxygen 1O2 under NIR laser irradiation, thereby inducing mitochondria-targeted damages and eliciting strong systemic immunogenic cell death immune responses. The combination of the I2HCy-QAP-mediated photodynamic immunotherapy with anti-programmed death-1 antibody therapy achieves remarkable therapeutic efficacy against both primary and distal metastatic cancers with significant inhibition of lung metastasis in a triple-negative breast cancer model. This work provides a new concept for designing high-performance NIR emissive cyanine immunomodulators for NIR-II fluorescence-guided photodynamic immunotherapy.
Insights
A novel photosensitizer targets cancer mitochondria for enhanced photodynamic immunotherapy. This approach improves treatment of primary and metastatic cancers, offering a new strategy for advanced cancer care.
Area of Science:
- Biomedical Engineering
- Oncology
- Photochemistry
Background:
- Photodynamic therapy (PDT) shows promise for cancer treatment, but current photosensitizers (PSs) have limitations in potency, mitochondria delivery, and treating metastatic disease.
- Effective PDT requires efficient delivery of PSs to cancer cell mitochondria and potent reactive oxygen species (ROS) generation.
Purpose of the Study:
- To develop an active self-mitochondria-targeting heptapeptide cyanine (HCy) immunomodulator (I2HCy-QAP) for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic immunotherapy.
- To evaluate the efficacy of I2HCy-QAP in treating primary and distal metastatic cancers, including triple-negative breast cancer.
Main Methods:
- Synthesized I2HCy-QAP by incorporating a lipophilic cationic quaternary ammonium salt with a phenethylamine skeleton (QAP) into an iodinated HCy photosensitizer.
- Utilized NIR-II fluorescence imaging for precise guidance and assessed singlet oxygen (1O2) generation under NIR laser irradiation.
- Investigated mitochondria-targeted damage and systemic immunogenic cell death (ICD) responses.
- Combined I2HCy-QAP mediated PDT with anti-programmed death-1 (PD-1) antibody therapy in a triple-negative breast cancer model.
Main Results:
- I2HCy-QAP demonstrated precise mitochondria targeting due to the QAP unit and strong NIR-II fluorescence emission.
- Effective generation of 1O2 under NIR laser irradiation induced mitochondria-targeted damage and potent systemic ICD.
- Combination therapy significantly inhibited primary and distal metastatic tumors, including lung metastasis, in the cancer model.
- Achieved remarkable therapeutic efficacy against both primary and distal metastatic cancers.
Conclusions:
- I2HCy-QAP is a high-performance NIR-II emissive cyanine immunomodulator with self-mitochondria-targeting capabilities.
- This approach enables effective NIR-II fluorescence-guided photodynamic immunotherapy for primary and metastatic cancers.
- The developed strategy offers a promising new concept for advanced cancer treatment by combining targeted PDT and immunotherapy.
