Table 2.

Nanosensors for TBIs with key features and therapeutic strategies

Chapter	Materials	Key features & nanosensing strategy	Applications
4.1	Peptide-based nanosensors	Calpain-1 activity-responsive peptide nanosensor with PEG scaffold for activity-based TBI diagnosis.	Real-time detection of calpain-1 activity for early-stage TBI diagnosis.
4.2	ECM-targeted nanosensors	ECM-targeted nanosensor modified with HA-binding peptides to enhance accumulation and cleavage by calpain-1.	Enhanced accumulation and sensitivity of nanosensors at the injured ECM in TBI.
4.3	Biomarker-responsive nanosensors	Activity-based nanosensor releasing cleaved peptide biomarker into biofluids for minimally invasive detection.	Minimally invasive measurement of protease activity through blood or urine analysis.
4.4	Polymer-based nanosensors	Polymeric nanosensor combining CAST and FRET substrate peptide for activity sensing and inhibition.	Simultaneous detection and inhibition of calpain activity to mitigate secondary injury in TBI.
4.5	Fibrinogen-based nanosensors	Fibrinogen-modified nanosensor using click chemistry for selective localization at fibrin clots in TBI site.	Targeted localization of therapeutic and diagnostic agents at TBI-associated clots.

ECM: extracellular matrix HA: Hyaluronic acid. CAST: Calpain inhibitory peptide. FRET: Fluorescence resonance energy transfer