Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids

Area of Science:

• Biomedical Engineering
• Cancer Research
• Optical Imaging

Background:

• Multicellular tumor spheroids (MTS) are valuable in vitro models for studying cancer therapies due to their ability to mimic tumor microenvironments, including hypoxia and drug resistance.
• Current analysis methods for MTS often compromise their 3D structure and function, limiting detailed investigation.
• There is a need for non-destructive techniques to assess the bioenergetic status and therapeutic response of MTS.

Purpose of the Study:

• To develop and validate a novel optical technique for in situ 3D mapping of redox potential gradients in MTS.
• To establish redox potential gradient as a quantitative measure of MTS viability and response to therapy.
• To demonstrate the utility of this technique in evaluating responses to radiotherapy and drug resistance.

Main Methods:

• Development of targeted nanosensors for optical imaging within MTS.
• In situ 3D mapping of redox potential gradients using the nanosensor technology.
• Quantification of the redox potential gradient as a free energy difference (ΔG).
• Correlation of ΔG measurements with varying doses of radiotherapy and drug treatments.

Main Results:

• The optical nanosensor technique successfully mapped 3D redox potential gradients in MTS without compromising morphology or function.
• A decrease in the free energy difference (ΔG) correlated with increasing doses of radiotherapy, indicating loss of viability.
• An increase in ΔG was observed in MTS resistant to drug therapy, signifying altered bioenergetic states.
• The technique proved robust and reproducible for interrogating MTS bioenergetic responses.

Conclusions:

• The developed optical nanosensor technique provides a non-destructive method for assessing MTS viability and response to cancer therapies.
• Redox potential gradient (ΔG) serves as a reliable indicator of MTS bioenergetic status and therapeutic outcomes.
• This technology holds significant potential as a tool for accelerating the development and evaluation of novel cancer therapies.