Related Experiment Video
Updated: Aug 5, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
A single-molecule prodrug synergistically suppresses MYC-amplified osteosarcoma through sequential nitric oxide
Shuxin Peng1, Jiangpeng Wu2, Shasha Wang1
1State Key Laboratory of Advanced Fiber Materials College of Chemistry and Chemical Engineering Donghua University Shanghai China.
Abstract:
MYC-amplified osteosarcoma, a poor-prognosis molecular subtype, presents formidable therapeutic challenges due to its aggressive phenotype, chemoresistance, and the "undruggable" oncogenic driver MYC. A single-molecule prodrug, DHU-NO3, was developed to achieve precise synergy between photodynamic therapy (PDT) and nitric oxide (NO) gas therapy for the treatment of MYC-amplified osteosarcoma. This prodrug covalently links the clinically approved photosensitizer methylene blue (MB) to an NO donor and undergoes a sequential activation cascade: reactive oxygen species-triggered MB release, 405 nm light-controlled NO generation, and PDT initiation under 650 nm laser irradiation. In 143B osteosarcoma cells, this temporally coordinated regimen efficiently induces apoptosis and potently suppresses the MYC signaling network. In the 143B osteosarcoma subcutaneous xenograft model, DHU-NO3-mediated sequential phototherapy demonstrated robust tumor growth inhibition with favorable biosafety. This work establishes a spatiotemporally programmable prodrug platform and provides a potent strategy to combat MYC-amplified osteosarcoma by indirect pathway suppression.
Insights
A novel DHU-NO3 prodrug combines photodynamic therapy and nitric oxide gas therapy to treat MYC-amplified osteosarcoma. This approach effectively inhibits tumor growth and suppresses MYC signaling with good biosafety.
Area of Science:
- Oncology
- Biomedical Engineering
- Drug Delivery
Background:
- MYC-amplified osteosarcoma is a challenging subtype with poor prognosis.
- The MYC oncogene is a difficult therapeutic target, contributing to aggressive disease and chemoresistance.
Purpose of the Study:
- To develop a novel prodrug, DHU-NO3, for synergistic photodynamic therapy (PDT) and nitric oxide (NO) gas therapy.
- To target MYC-amplified osteosarcoma through a spatiotemporally controlled sequential activation cascade.
Main Methods:
- DHU-NO3 prodrug synthesis, linking methylene blue (MB) and an NO donor.
- Sequential activation triggered by reactive oxygen species and light (405 nm for NO, 650 nm for PDT).
- In vitro studies on 143B osteosarcoma cells and in vivo studies using a 143B xenograft model.
Main Results:
- DHU-NO3 demonstrated ROS-triggered MB release and light-controlled NO generation.
- The sequential therapy induced apoptosis and suppressed MYC signaling in osteosarcoma cells.
- DHU-NO3 treatment significantly inhibited tumor growth in vivo with favorable biosafety.
Conclusions:
- DHU-NO3 establishes a spatiotemporally programmable prodrug platform.
- This strategy offers a potent approach to combat MYC-amplified osteosarcoma by indirectly suppressing MYC signaling.
