Biofunctionalized nanomaterials for Parkinson's disease theranostics: potential for efficient PD biomarker detection and effective therapy

α-Synuclein (α-Syn) is a primary pathological indicator for Parkinson's disease (PD). The α-Syn oligomer is even more toxic and is responsible for PD. Hence, identifying α-Syn and its oligomers is an interesting approach to diagnosing PD. The prevention strategies for oligomer formation could be therapeutic in treating PD. Various conventional strategies have been developed for the management of PD. However, their clinical applications are limited due to toxicity, off-targeting, side effects, and poor bioavailability. Recently, nanomaterials have gained significant attention due to unique physicochemical characteristics such as nanoscale size, large surface area, flexibility of functionalization, and ability to protect and control a loaded payload. Functionalizing the surface of nanoparticles with a desired targeting agent could offer targeted delivery of the payload at the site of action due to specificity and selectivity against complementary molecules. Among various functionalization approaches, biomolecule-functionalized nanomaterials offer benefits such as enhanced bioavailability, improved internalization into target cells through receptor-mediated endocytosis, and delivery of therapeutics across the BBB (blood-brain barrier). In this review, we initially discussed the major milestones related to PD and highlighted the therapeutic strategies focused on clinical trials. The strategies of biomolecule functionalization of nanomaterials and their application in detecting and preventing α-Syn oligomer for the diagnosis and therapy of PD, respectively, have been reviewed comprehensively. Ultimately, we have outlined the conclusions, highlighted the limitations and challenges, and provided insight into future perspectives and alternative approaches that must be investigated.