Functional nanoprobes for early diagnosis and precision theranostics of Parkinson's disease: a review of material strategies and multimodal sensing.

The pressing need for early and accurate diagnosis of Parkinson's disease (PD) has motivated the development of advanced nanoscale diagnostic tools. Functional nanoprobes, owing to their tunable physicochemical properties and versatile surface chemistry, have emerged as powerful platforms for the sensitive and selective detection of PD-related biomarkers, including α-synuclein aggregates, dysregulated metal ions, and neurotransmitters. Unlike conventional diagnostic modalities such as cerebrospinal fluid analysis or neuroimaging, which suffer from invasiveness, high cost, and limited specificity, nanoprobe-based strategies enable minimally invasive, real-time, and multimodal sensing with high spatial and temporal resolution. Prior reviews of PD nanotechnology have focused on drug delivery systems or individual nanomaterial categories. The present review addresses three under-explored aspects: (i) the rational design and functional modification of nanoprobes for enhanced blood-brain barrier penetration and targeted delivery, (ii) the systematic integration of multimodal sensing architectures across multiple PD biomarker types (protein aggregates, neurotransmitters, metal ions, and enzyme activities), and (iii) the logical continuum from precision diagnosis to closed-loop theranostic platforms. We highlight key material strategies, including organic, inorganic, and hybrid nanosystems, as well as surface functionalization approaches for enhanced blood-brain barrier penetration and targeted biomarker identification. Furthermore, we examine the emerging opportunities for combining diagnostic and therapeutic functions within a single nanoprobe platform, paving the way for precision theranostics. Finally, a critical assessment of current challenges and future perspectives for clinical translation provides insights for the development of next-generation nanomaterial-based tools for early PD management.