Antibody-Free Detection of Tau Peptide with <scp>l</scp>-Arginine-Ligated Polyacrylic Acid-Capped Upconversion Nanoparticle

Early diagnosis of Alzheimer’s disease, a progressive neurodegenerative disorder, is highly demanding in the global health sector since its complete cure and treatment protocols are still a challenge. Despite the prevalence of this disease, traditional methods such as PET scanning and invasive CSF extraction methods are costly and complex in nature. However, these techniques are not suitable for early detection specifically in resource-limited settings. Hence, it is high time to focus on the advancement of developing a non-invasive approach for detection of the tau peptide, a key blood-based biomarker of Alzheimer’s disease. In this study, we have developed an antibody-free nanoprobe based on the l-arginine-ligated poly(acrylic acid) (PAA)-capped LiYF4:Yb, Tm photon upconversion nanoparticle (l-Arg@PAA@LiYF4:Yb, Tm). Initially, blue fluorescent LiYF4:Yb, Tm nanoparticles were synthesized with emission at the blue region (λex 980 nm, λem 480 nm), which exhibit a crystalline structure as evident from XRD and HR-TEM analyses. The synthesized nanoparticles were further surface functionalized with a negatively charged hydrophilic polymer, PAA, followed by quenching the upconversion luminescence with positively charged l-arginine by an electrostatic interaction. Furthermore, addition of the tau peptide bound the guanidinium moiety of l-arginine resulting in luminescence recovery of nanoparticles in a linear concentration range of 49.18–477.7 pg/mL. The probe showed low LoD and LoQ of 5.01 and 16.7 pg/mL, respectively. The designed probes exhibited good selectivity and low interference with competing proteins and biomarkers. The biological validation was studied in spiked human serum samples with adequate recovery percentages (96–105%), indicating the relevance of the probe in designing non-invasive, economical, and viable point-of-care device platforms for the early diagnosis of the tau peptide and associated neurodegenerative disorders.