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Updated: May 2, 2026
Affordable Oxygen Microscopy-Assisted Biofabrication of Multicellular Spheroids
Published on: April 6, 2022
Click-assembled, oxygen-sensing nanoconjugates for depth-resolved, near-infrared imaging in a 3D cancer model
Alexander J Nichols1, Emmanuel Roussakis, Oliver J Klein
1Wellman Center for Photomedicine, Massachusetts General Hospital, CNY 149-3210, 13th Street, Charlestown, MA 02129 (USA); Harvard University Program in Biophysics, Building C2 Room 112, 240 Longwood Avenue, Boston, MA 02115 (USA); Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue E25-519, Cambridge, MA 02139 (USA).
Abstract:
Hypoxia is an important contributing factor to the development of drug-resistant cancer, yet few nonperturbative tools exist for studying oxygenation in tissues. While progress has been made in the development of chemical probes for optical oxygen mapping, penetration of such molecules into poorly perfused or avascular tumor regions remains problematic. A click-assembled oxygen-sensing (CAOS) nanoconjugate is reported and its properties demonstrated in an in vitro 3D spheroid cancer model. The synthesis relies on the sequential click-based ligation of poly(amidoamine)-like subunits for rapid assembly. Near-infrared confocal phosphorescence microscopy was used to demonstrate the ability of the CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within hours and to show their sensitivity to oxygen changes throughout the nodule. This proof-of-concept study demonstrates a modular approach that is readily extensible to a wide variety of oxygen and cellular sensors for depth-resolved imaging in tissue and tissue models.
Insights
New click-assembled oxygen-sensing (CAOS) nanoconjugates can penetrate deep into 3D cancer models to map oxygen levels. This tool addresses limitations of current methods for studying hypoxia in drug-resistant tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Hypoxia, or low oxygen, is a key factor in drug-resistant cancer development.
- Current optical oxygen mapping tools struggle to penetrate poorly perfused tumor regions.
- There is a need for nonperturbative tools to study tissue oxygenation.
Purpose of the Study:
- To develop and demonstrate a novel click-assembled oxygen-sensing (CAOS) nanoconjugate.
- To evaluate the CAOS nanoconjugate's ability to penetrate and sense oxygen in a 3D cancer model.
- To establish a modular platform for depth-resolved oxygen imaging in tissues.
Main Methods:
- Synthesis of CAOS nanoconjugates via sequential click-based ligation of poly(amidoamine)-like subunits.
- Utilizing near-infrared confocal phosphorescence microscopy for imaging.
- Testing in an in vitro 3D spheroid cancer model.
Main Results:
- CAOS nanoconjugates demonstrated rapid assembly and modularity.
- Nanoconjugates successfully penetrated hundreds of micrometers into 3D spheroids within hours.
- The probes accurately detected oxygen level changes throughout the tumor model.
Conclusions:
- CAOS nanoconjugates offer a promising solution for deep-tissue oxygen sensing.
- The modular platform is adaptable for various sensors and tissue models.
- This technology can advance the study of hypoxia in drug-resistant cancers.
