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Updated: Dec 21, 2025
Biofunctionalized Prussian Blue Nanoparticles for Multimodal Molecular Imaging Applications
Published on: April 28, 2015
Biodegradable Poly(γ-glutamic acid)@glucose oxidase@carbon dot nanoparticles for simultaneous multimodal imaging and
Ming Zhang1, Wentao Wang1, Fan Wu2
1Department of Health Technology, Technical University of Denmark, Kongens Lyngby, DK-2800, Denmark; Jiangsu Collaborative Innovation Center for Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China.
Abstract:
It is known that tumor antigens could induce obvious anti-tumor immune responses for efficient cancer immunotherapy when combined with checkpoint blockade. However, the amount of tumor antigens is often limited due to the suppressive tumor microenvironment (TME). Here, a new type of nanomaterial was developed to improve tumor treatment by the combined action of starving therapy/photodynamic therapy (PDT)/photothermal therapy (PTT) and checkpoint-blockade immunotherapy. In detail, the immunoadjuvant nanoagents (γ-PGA@GOx@Mn,Cu-CDs) were fabricated by integrating the gamma-glutamyl transferase (GGT) enzyme-induced cellular uptake polymer-poly (γ-glutamic acid) (γ-PGA), a glucose-metabolic reaction agent - glucose oxidase (GOx), Mn,Cu-doped carbon dots (CDs) as photosensitizer and self-supplied oxygenator nanodots. γ-PGA@GOx@Mn,Cu-CDs nanoparticles (NPs) showed long retention time at the tumor acidic microenvironment and could further target cancer cells. The NPs also displayed both photothermal and photodynamic effects under laser irradiation at 730 nm. Interestingly, the endogenous generation of hydrogen peroxide (H2O2) caused by the nanoreactors could significantly relieve tumor hypoxia and further enhance in vivo PDT. By synergistically combining the NPs-based starving-like therapy/PDT/PTT and check-point-blockade therapy, the treatment efficiency was significantly improved. More importantly, the systematic antitumor immune response would eliminate non-irradiated tumors as well, which is promising for metastasis inhibition.
Insights
This study introduces novel nanoparticles combining starving, photodynamic, and photothermal therapies with checkpoint blockade immunotherapy. This synergistic approach enhances anti-tumor immunity and inhibits metastasis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Tumor antigens are crucial for effective cancer immunotherapy when combined with checkpoint blockade.
- The tumor microenvironment (TME) often limits tumor antigen availability, hindering treatment efficacy.
- Novel strategies are needed to overcome TME suppression and enhance immunotherapy.
Purpose of the Study:
- To develop multifunctional nanoparticles for combined starving therapy, photodynamic therapy (PDT), photothermal therapy (PTT), and checkpoint-blockade immunotherapy.
- To investigate the efficacy of these nanoparticles in improving tumor treatment and stimulating systemic anti-tumor immune responses.
- To assess the potential of this approach for inhibiting metastasis.
Main Methods:
- Fabrication of immunoadjuvant nanoagents (γ-PGA@GOx@Mn,Cu-CDs) integrating poly (γ-glutamic acid) (γ-PGA), glucose oxidase (GOx), and Mn,Cu-doped carbon dots (CDs).
- Evaluation of nanoparticle retention in acidic tumor microenvironments and targeting of cancer cells.
- Assessment of photothermal and photodynamic effects under laser irradiation (730 nm) and the role of hydrogen peroxide (H2O2) in relieving tumor hypoxia.
Main Results:
- The nanoparticles demonstrated long retention in acidic TME and targeted cancer cells.
- Combined starving-like therapy, PDT, and PTT with checkpoint blockade significantly improved treatment efficiency.
- Endogenous H2O2 generation by nanoreactors relieved tumor hypoxia, enhancing in vivo PDT.
- A systemic anti-tumor immune response was induced, leading to the elimination of non-irradiated tumors.
Conclusions:
- The developed γ-PGA@GOx@Mn,Cu-CDs nanoparticles offer a promising platform for synergistic cancer therapy.
- This multi-modal approach effectively enhances anti-tumor immunity and shows potential for metastasis inhibition.
- Targeted delivery and TME modulation are key factors in improving cancer immunotherapy outcomes.
