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Updated: Jul 1, 2025
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared photoactivatable
Yue Liu1, Renjie Lu2, Meng Li1
1State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China. jcli@dhu.edu.cn.
Abstract:
Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.
Insights
This study introduces dual-enzyme nanoagents for cancer therapy. These agents use near-infrared light to trigger enzyme release, enhancing ferroptosis and reversing immunosuppression for improved tumor treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Enzyme activity regulation is crucial for effective cancer treatment.
- Developing precise therapeutic strategies for cancer remains a challenge.
Purpose of the Study:
- To develop dual-enzyme decorated semiconducting polymer nanoagents for photoactivatable ferroptosis-immunotherapy.
- To precisely control enzyme release and activity for enhanced cancer treatment.
Main Methods:
- Fabrication of SPHGA nanoagents incorporating hemoglobin-based semiconducting polymer, adenosine deaminase (ADA), and glucose oxidase (GOx).
- Utilized near-infrared (NIR-II) light to trigger heat-induced release of ADA and GOx from thermal-responsive nanoparticle shells.
- Investigated the synergistic effects of ferroptosis, immunogenic cell death (ICD), and immune microenvironment modulation in a 4T1 breast cancer model.
Main Results:
- NIR-II photoactivation successfully released ADA and GOx, inducing ferroptosis via H2O2 generation and Fenton reactions.
- ADA effectively degraded immunosuppressive adenosine, reversing the tumor microenvironment.
- SPHGA demonstrated significant efficacy in eliminating bilateral tumors and suppressing metastasis in vivo.
Conclusions:
- Dual-enzyme nanoagents offer a controllable platform for precise cancer therapy.
- Photoactivatable ferroptosis-immunotherapy presents a promising strategy for overcoming tumor progression and metastasis.
- This approach enhances antitumor immune responses by modulating the tumor microenvironment.
