Related Experiment Videos
Upconversion nanoparticle-based optogenetic nanosystem for photodynamic therapy and cascade gene therapy
Xinyue Song1, Fengyan Li2, Feng Tian2
1Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Medicine, Linyi University, Linyi 276005, PR China.
Acta Biomaterialia
|December 9, 2022
Summary
This study introduces a novel upconversion nanoparticle (UCNP)-based system for precise cancer treatment, combining bio-imaging, photodynamic therapy (PDT), and gene therapy. The system uses genetically-encoded photosensitizers activated by near-infrared light for enhanced tumor inhibition.
Area of Science:
- Biomedical Engineering
- Optogenetics
- Nanotechnology
Background:
- Traditional photodynamic therapy (PDT) using organic dyes faces limitations like poor cell uptake and off-target toxicity.
- Genetically-encoded photosensitizers offer precise, single-cell targeting but are hindered by shallow light penetration and low apoptosis ratios.
- Existing methods lack integrated approaches for enhanced therapeutic efficacy in deep tissues.
Purpose of the Study:
- To develop a multifunctional upconversion nanoparticle (UCNP)-based optogenetic nanosystem for enhanced photodynamic therapy (PDT) and cascade gene therapy.
- To achieve targeted cancer cell elimination with improved precision and therapeutic performance.
- To overcome the limitations of shallow light penetration and low apoptosis ratios associated with genetically-encoded photosensitizers.
Main Methods:
- Constructed a mitochondria-targeted genetically-encoded photosensitizer and transfected it into cancer cells.
- Developed a UCNP-based nanoprobe with mitochondria targetability and siRNA loading via a reactive oxygen species (ROS)-sensitive bond.
- Utilized near-infrared (NIR) irradiation to activate UCNP emission, triggering ROS generation and subsequent siRNA release for combined PDT and gene therapy.
Main Results:
- Successfully accumulated both UCNPs and genetically-encoded photosensitizers in cancer cell mitochondria.
- Achieved NIR-triggered, mitochondria-localized generation of ROS and controllable siRNA release.
- Demonstrated activation of mitochondria-mediated apoptosis pathways, leading to significant tumor growth inhibition.
Conclusions:
- Developed the first NIR laser-activated, organelle-localized genetically-encoded photosensitizer system for cascade therapy.
- The UCNP-based nanosystem enhances PDT and gene therapy efficacy for malignant tumors.
- This approach holds promise for advancing optogenetic tools in precise tumor treatment.