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Published on: July 3, 2018
Real-Time Visualization of Lysosome Destruction Using a Photosensitive Toluidine Blue Nanogel
Weiqi Zhang1, Ching-Hsuan Tung1
1Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, 413 East 69th Street, Box 290, New York, NY, 10021, USA.
Abstract:
Breaking the lysosome helps its sequestered payloads access their molecular targets in cells and thus enhances the intracellular drug delivery. Current strategies for lysosomal escape involve direct physical interactions with the lipid membrane. These interactions pose a systemic toxicity and uncontrolled membrane rupture risk. Here, we report a light-detonated lysosome disruption using a hyaluronan (HA) nanogel packed with toludine blue (TB). The HA/TB nanogel is concentrated within the lysosomes. The applied light assists TB in generating reactive oxygen species and destroying the lysosome in situ, both in cells and isolated lysosomes. Real time fluorescent tracking reveals that quenched TB fluorescence recovers along with lysosome explosion, relocates to the nucleus, and is presented as a fluorescent sparkling in cells. This HA/TB, composed of all clinically approved materials, represents a biocompatible and facile strategy to "bomb" lysosomes in a spatiotemporally controlled fashion.
Insights
Researchers developed a light-activated nanogel to safely break open lysosomes for enhanced intracellular drug delivery. This method uses clinically approved materials for controlled drug release, minimizing toxicity risks associated with current approaches.
Area of Science:
- Biotechnology
- Nanomedicine
- Cell Biology
Background:
- Lysosomal disruption is key for intracellular drug delivery.
- Current methods risk toxicity and uncontrolled membrane rupture.
- Novel strategies are needed for safe and controlled lysosomal escape.
Purpose of the Study:
- To develop a light-detonated system for lysosomal disruption.
- To utilize clinically approved materials for enhanced biocompatibility.
- To achieve spatiotemporally controlled intracellular drug delivery.
Main Methods:
- Hyaluronan (HA) nanogels were formulated with toludine blue (TB).
- HA/TB nanogels were concentrated within lysosomes.
- Light activation triggered reactive oxygen species generation for lysosome destruction.
Main Results:
- Light-activated TB within HA nanogels effectively disrupted lysosomes in situ.
- Fluorescence tracking confirmed lysosomal escape and nuclear translocation.
- The system demonstrated biocompatibility using clinically approved components.
Conclusions:
- Light-detonated HA/TB nanogels offer a safe and controlled method for lysosomal disruption.
- This approach enhances intracellular drug delivery potential.
- The strategy minimizes risks associated with physical membrane disruption.
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