Minimally Invasive Delivery of Optical Nanosensors Using Injectable Hydrogels

ABSTRACT Optimizing treatment plans based on an individual's drug concentration can significantly improve therapeutic outcomes, as drug efficacy is closely linked to its plasma levels. This motivates the development of precise tools for measuring drug concentration in situ. To address this, a minimally invasive optical sensing platform based on preformed, injectable hydrogels that encapsulate near‐infrared fluorescent single‐walled carbon nanotube (SWCNT) sensors is introduced. DNA‐suspended SWCNTs are integrated into self‐assembling peptide hydrogels reinforced with natural polysaccharide additives, yielding self‐healing, shear‐thinning gels that can be injected through a fine needle while maintaining both structural integrity and optical functionality. A model target analyte, levodopa, the primary treatment for Parkinson's disease, was chosen. The encapsulated SWCNTs exhibit a levodopa‐induced dose‐dependent fluorescence response across physiologically relevant concentrations. Importantly, the SWCNTs within the hydrogel retain their fluorescence response to levodopa following injection, in the presence of serum, and in a subcutaneous tissue phantom that mimics the mechanical and optical scattering properties of soft tissue. These results establish preformed injectable peptide‐based hydrogels as a new class of function‐preserving materials for the localized deployment of SWCNT optical nanosensors, enabling minimally invasive in situ monitoring of drug levels and offering a potential route toward personalized therapeutic drug monitoring.