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Updated: Jun 27, 2025
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy
Bingbing Sun1, Haowen Yang2, Yudong Li1
1Bio-Organic Chemistry, Department of Chemical Engineering and Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology Helix, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Abstract:
Photodynamic therapy (PDT) has demonstrated efficacy in eliminating local tumors, yet its effectiveness against metastasis is constrained. While immunotherapy has exhibited promise in a clinical context, its capacity to elicit significant systemic antitumor responses across diverse cancers is often limited by the insufficient activation of the host immune system. Consequently, the combination of PDT and immunotherapy has garnered considerable attention. In this study, we developed pH-responsive porphyrin-peptide nanosheets with tumor-targeting capabilities (PRGD) that were loaded with the IDO inhibitor NLG919 for a dual application involving PDT and immunotherapy (PRGD/NLG919). In vitro experiments revealed the heightened cellular uptake of PRGD/NLG919 nanosheets in tumor cells overexpressing αvβ3 integrins. The pH-responsive PRGD/NLG919 nanosheets demonstrated remarkable singlet oxygen generation and photocytotoxicity in HeLa cells in an acidic tumor microenvironment. When treating HeLa cells with PRGD/NLG919 nanosheets followed by laser irradiation, a more robust adaptive immune response occurred, leading to a substantial proliferation of CD3+CD8+ T cells and CD3+CD4+ T cells compared to control groups. Our pH-responsive targeted PRGD/NLG919 nanosheets therefore represent a promising nanosystem for combination therapy, offering effective PDT and an enhanced host immune response.
Insights
This study introduces pH-responsive nanosheets combining photodynamic therapy (PDT) and immunotherapy. This dual-action approach enhances T cell proliferation and antitumor responses, offering a promising strategy for cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) effectively treats local tumors but struggles with metastasis.
- Immunotherapy shows promise but often lacks sufficient host immune activation for systemic antitumor effects.
- Combining PDT and immunotherapy is a promising strategy to overcome individual limitations.
Purpose of the Study:
- To develop pH-responsive, tumor-targeting porphyrin-peptide nanosheets (PRGD) loaded with an IDO inhibitor (NLG919).
- To evaluate the dual application of PDT and immunotherapy (PRGD/NLG919) for enhanced cancer treatment.
- To investigate the nanosystem's efficacy in vitro and its impact on the host immune response.
Main Methods:
- Development of pH-responsive, tumor-targeting (αvβ3 integrin) porphyrin-peptide nanosheets (PRGD).
- Loading of Indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 into nanosheets (PRGD/NLG919).
- In vitro assessment of cellular uptake, singlet oxygen generation, photocytotoxicity, and immune response (T cell proliferation) in HeLa cells.
Main Results:
- PRGD/NLG919 nanosheets showed enhanced uptake in tumor cells overexpressing αvβ3 integrins.
- Nanosheets demonstrated significant singlet oxygen generation and photocytotoxicity in an acidic tumor microenvironment.
- Combination therapy with PRGD/NLG919 and laser irradiation significantly increased CD3+CD8+ and CD3+CD4+ T cell proliferation.
Conclusions:
- pH-responsive targeted PRGD/NLG919 nanosheets are a viable platform for combined PDT and immunotherapy.
- This nanosystem effectively enhances host immune response and offers potential for improved cancer treatment.
- The dual-action approach shows promise in overcoming limitations of PDT and immunotherapy alone.
