Dual-responsive carbon dot probe utilizing proton exchange and aggregation for correlating biomarker levels with postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a severe complication of varicella-zoster virus (VZV) infection, for which there are currently no reliable objective tools for early prediction. Current post-VZV risk assessment mainly relies on clinical symptoms, which show limited accuracy in identifying individuals who will develop PHN. Biomarker-based strategies that can improve predictive performance are therefore urgently needed. Herein, a dual-responsive nanoprobe is developed for the simultaneous detection of two complementary indicators of neuronal injury (neuron-specific enolase, NSE) and demyelination (myelin basic protein, MBP) in human plasma. Based on the features of NSE and MBP, a carbon dot-based platform with 2-phosphoglyceric acid, paramagnetic Gd, and MBP antibody has been designed. On the platform, 2-phosphoglyceric acid and paramagnetic Gd are used to detect NSE via dehydration and proton exchange (producing a nuclear magnetic resonance response), respectively, while the MBP antibody links the platform to MBP, leading to aggregation-induced emission of carbon dots. The limit of detection values of the dual-responsive nanoprobe for NSE and MBP detection are 0.02 and 0.15 pg/mL, respectively, and the cut-off concentrations for differentiating PHN-suffering patients from VZV-infected patients are 21.50 and 10.10 ng/mL, respectively. These results demonstrate the feasibility of the dual-responsive nanoprobe for PHN discrimination. Importantly, the NSE and MBP levels after skin rash are reliable to be correlated with PHN due to the significant correlations between biomarker concentration and pain severity after PHN. This work demonstrates a dual-biomarker sensing strategy that improves detection accuracy and provides a potential tool for PHN risk prediction and stratification following VZV infection.