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Photo-PISA Driven In Situ Encapsulation of Nanocluster-Based Sensors within Stimuli-Responsive Polymersomes for AND
Kaili Chen1, Colleen N Loynachan1, Chalaisorn Thanapongpibul1
1Department of Materials, Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, SW7 2AZ London, U.K.
ACS Sensors
|November 2, 2025
Summary
This study introduces a dual-sensing platform using gold nanoclusters within pH-responsive polymersomes. It enables specific colorimetric detection of enzymes in acidic environments, improving diagnostic accuracy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Analytical Chemistry
Background:
- Colorimetric sensing offers simplicity and speed for medical diagnostics.
- Enhancing sensitivity and specificity of assays for endogenous enzymes in complex diseases is challenging.
- Existing methods struggle with background noise and specificity in biological samples.
Purpose of the Study:
- To develop a hierarchical AND logic gate dual-sensing platform for improved enzyme detection.
- To integrate gold nanoclusters (AuNCs) as nanozymes with a carrier protein and pH-responsive polymersomes.
- To achieve specific and sensitive detection of target enzymes in acidic microenvironments.
Main Methods:
- Synthesized pH-responsive polymersomes via photoinitiated polymerization-induced self-assembly (photo-PISA).
- Encapsulated peptide-templated AuNCs tethered to a carrier protein within the polymersomes.
- Utilized an AND logic gate mechanism for dual-responsive release and colorimetric readout.
Main Results:
- The AuNC-protein complex was released from polymersomes under acidic conditions.
- Target enzyme presence triggered cleavage of AuNCs from the protein complex.
- A positive colorimetric signal was generated only in the presence of both acidic conditions and the target enzyme.
Conclusions:
- The developed AND logic gate platform enhances specificity and minimizes background signals.
- This system is suitable for complex biological environments and dual-responsive in vivo sensing.
- Potential applications include detecting overexpressed enzymes in acidic tumor or inflammatory microenvironments with a urinary readout.

