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Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Semiconducting Polymer Nano-regulators with Cascading Activation for Photodynamic Cancer Immunotherapy
Shasha He1, Jing Liu2,3,4,5, Chi Zhang1
1School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
Abstract:
Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPNT ) with cascading activation for combinational photodynamic cancer immunotherapy. SPNT comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPNT produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPNT -mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.
Insights
This study introduces a smart semiconducting polymer nano-regulator for cancer immunotherapy. It combines photodynamic therapy with immune regulation to effectively suppress tumors and prevent metastasis.
Area of Science:
- Biomaterials Science
- Cancer Immunotherapy
- Nanotechnology
Background:
- Combination photoimmunotherapy shows promise for tumor suppression.
- Development of smart phototherapeutic agents with tumor-specific activation remains a challenge.
Purpose of the Study:
- To develop a semiconducting polymer nano-regulator (SPNT) with cascading activation for combinational photodynamic cancer immunotherapy.
- To investigate the efficacy of SPNT in reprogramming the tumor immune microenvironment and inhibiting tumor growth and metastasis.
Main Methods:
- Synthesized SPNT comprising a semiconducting polymer backbone conjugated with 1-methyltryptophan (M-Trp) via an apoptotic biomarker-cleavable linker.
- Utilized near-infrared photoirradiation to activate SPNT, inducing singlet oxygen production and immunogenic apoptosis.
- Demonstrated M-Trp cleavage triggered by upregulated apoptotic biomarkers, leading to indoleamine 2,3-dioxygenase (IDO) inhibition.
Main Results:
- SPNT induced immunogenic apoptosis and singlet oxygen production upon near-infrared irradiation.
- Cleavage of M-Trp specifically inhibited IDO activity, reduced regulatory T cells, and enhanced cytotoxic T lymphocytes infiltration.
- SPNT-mediated therapy effectively suppressed primary tumors and inhibited lung metastasis in preclinical models.
Conclusions:
- SPNT represents a novel smart nano-regulator for dual-action cancer immunotherapy.
- The cascading activation strategy effectively reprograms the tumor immune microenvironment for enhanced therapeutic outcomes.
- This approach holds significant potential for treating primary tumors and preventing metastatic spread.
