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Updated: Jul 5, 2025
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
ATP-adenosine axis regulation combined with microneedle assisted photoimmunotherapy to boost the immunotherapy
Chaonan Shi1, Minglong Chen2, Xiaodie Li1
1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; College of Pharmacy, Jinan University, Guangzhou 510632, China.
Abstract:
Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy.
Insights
This study introduces a novel microneedle patch delivering an immunogenic cell death (ICD) inducer and CD39 inhibitor. This combination effectively targets tumors by modulating the ATP-adenosine axis for enhanced antitumor immunity.
Area of Science:
- Oncology
- Immunology
- Materials Science
Background:
- Immunogenic cell death (ICD) releases damage-associated molecular patterns like ATP, crucial for anti-tumor immunity.
- Tumors degrade extracellular ATP via the CD39 enzyme, converting it to immunosuppressive adenosine, thus evading immune responses.
Purpose of the Study:
- To develop a dissolving microneedle patch (DMNs) for co-delivering an ICD inducer (IR780) and a CD39 inhibitor (POM-1) for synergistic antitumor therapy.
- To investigate the combined effects of phototherapy and CD39 inhibition on the tumor microenvironment and immune response.
Main Methods:
- Designing solid lipid nanoparticles (SLNs) co-encapsulating IR780 and POM-1 for DMNs delivery.
- Intralesional administration of DMNs into tumor sites in murine models.
- Evaluating tumor growth inhibition, ICD induction, and immune cell infiltration.
Main Results:
- The DMNs platform successfully induced ICD and released immunostimulatory ATP by inhibiting CD39.
- Significant tumor growth inhibition was observed in melanoma (96.5%) and colorectal adenocarcinoma (93.5%) models.
- The treatment promoted an anti-tumor immune response by modulating the ATP-adenosine axis.
Conclusions:
- The developed DMNs offer a promising strategy for combinatorial cancer immunotherapy by enhancing ICD and regulating the ATP-adenosine pathway.
- This approach holds potential for broadening the scope of synergistic antitumor immunotherapies.
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