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Updated: Jan 14, 2026
Affordable Oxygen Microscopy-Assisted Biofabrication of Multicellular Spheroids
Published on: April 6, 2022
Multifunctional nano-MOFs based on tumor microenvironment modulation for detecting singlet oxygen and enhancing
Yongdan Wang1, Linshan Jia1, Xiaotong Li1
1Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China.
Abstract:
Photodynamic therapy (PDT) has been extensively used in tumor therapy due to its excellent selectivity, minimal toxicity, and tolerability. However, several indicators in the tumor microenvironment (TME) are abnormal. The therapeutic impact of PDT is compromised due to 1O2 depletion caused by the overexpression of glutathione (GSH). Additionally, the concentration of 1O2 during the treatment is still undefined. Insufficient or excessive therapeutic effects could occur, making it impossible to achieve precise treatment. Accordingly, we designed a multifunctional nanosystem (DPA-MOF@MnO2-Ce6@PEG) that integrates a TME regulatory unit, 1O2 generation unit, and 1O2 detection probe to address the above problems. Upon laser radiation, the modification of MnO2 altered the amount of GSH in the TME, which reduced the depletion of 1O2 mediated by the photosensitizer Ce6, with the aim of augmenting the effectiveness of PDT. Concurrently, DPA-MOF captured the generated 1O2, and the fluorescence quenching of the probe provided feedback on the 1O2 level during PDT. A coating of polyethylene glycol (PEG) was used to enhance the dispersity of the nanoparticles and prevent the leakage of the photosensitizer. As expected, the designed multifunctional nanoparticles exhibited good detection capability towards 1O2, GSH depletion capacity, and potent antitumor activity in 4T1 and MCF-7 tumor cells. This work provided an insight into the precise treatment of PDT and a solution for the depletion of over-expressed GSH in TME to enhance PDT.
Insights
This study introduces a novel nanosystem to improve photodynamic therapy (PDT) by regulating the tumor microenvironment and detecting singlet oxygen (1O2). The system enhances PDT efficacy by reducing glutathione (GSH) depletion and enabling precise treatment monitoring.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Photodynamic Therapy
Background:
- Photodynamic therapy (PDT) is a promising cancer treatment but faces challenges from the tumor microenvironment (TME), including glutathione (GSH) overexpression that depletes singlet oxygen (1O2).
- The precise monitoring of 1O2 levels during PDT is crucial for optimizing therapeutic outcomes and avoiding insufficient or excessive treatment.
Purpose of the Study:
- To develop a multifunctional nanosystem for TME regulation, 1O2 generation, and real-time 1O2 detection to overcome PDT limitations.
- To enhance PDT efficacy by mitigating GSH-mediated 1O2 depletion and enabling accurate treatment control.
Main Methods:
- Design and synthesis of a DPA-MOF@MnO2-Ce6@PEG multifunctional nanosystem.
- Utilizing MnO2 to modulate GSH levels, Ce6 as a photosensitizer, DPA-MOF for 1O2 capture and detection, and PEG for stability.
- Evaluating the nanosystem's 1O2 detection capability, GSH depletion capacity, and antitumor activity in vitro using 4T1 and MCF-7 cells.
Main Results:
- The DPA-MOF@MnO2-Ce6@PEG nanosystem effectively detected 1O2 levels.
- The system demonstrated significant GSH depletion capacity within the TME.
- Potent antitumor activity was observed in 4T1 and MCF-7 tumor cells, indicating enhanced PDT efficacy.
Conclusions:
- The developed multifunctional nanosystem offers a promising strategy for precise PDT by addressing TME abnormalities and enabling real-time monitoring.
- This approach provides a viable solution for overcoming GSH-induced 1O2 depletion, thereby improving PDT outcomes in cancer therapy.
