Photonic hydrogels for monitoring extracellular vesicle mimics

Extracellular vesicles (EVs) mediate cell-to-cell communication in both physiological and pathological processes and hold potential for diagnostics and therapeutics. However, their intrinsic complexity and heterogeneity pose challenges for detection and analysis. Biosensors aim to overcome these limitations, offering sensitive, selective, simple, and cost-effective technologies for capturing and quantifying EVs. In this work, synthetic liposomes functionalized with the tetraspanin CD9 are developed as EV mimics (lipoCD9). These proteoliposomes are used as templates to fabricate imprinted hydrogels incorporating photonic structures for label-free detection. The proteoliposome imprinted photonic hydrogel (PIPH) exhibited a linear response to increasing concentrations of lipoCD9 (10³ to 10⁸ liposomes mL^-1), indicated by a red shift in the reflectance peak and changes in color coordinates. Visually, the PIPH sensor was distinguishable from the non-imprinted control, which exhibited only random variations. Selectivity studies confirmed that the PIPH sensor did not respond to liposomes modified with the tetraspanin CD81, demonstrating its ability to discriminate between liposomes surface-decorated with different peptides. In conclusion, the combination of selective imprinted hydrogels with label-free, structural color-based detection provides excellent recognition capabilities, offering a promising biomimetic platform that could support EV profiling efforts in biomedical applications.