A perspective on the selection and design of nanozyme-based aptasensors for small molecules

Nanozymes and aptamers have long been integral parts of the biosensing field. Recent advancements in these areas have culminated in the creation of a novel class of biosensors known as nanozyme-based aptasensors. In these sensors, aptamers confer specificity to the target analyte, while nanozymes function as transducers, converting a binding event (the binding of the aptamer to its target) into a detectable signal. Despite their promising potential and diverse applications, the detection of small-target molecules, like antibiotics, toxins, metal ions, etc., using nanozyme-based aptasensors remains challenging. This perspective focuses on the obstacles associated with the selection of aptamers for small targets, the design and efficiency of nanozymes, and their integration into functional sensors. In the current perspective, we outline the key challenges and propose various strategies to overcome these hurdles, drawing lessons from past failures to inspire further research for detection of small-target molecules. By incorporating these measures, the performance of nanozyme-based aptasensors to detect small-target molecules can be significantly improved, leading to more effective detection platforms with enhanced sensitivity in the near future. • This perspective focused on the design of nanozyme-based aptasensors for detecting small targets. • It discusses key challenges encountered while designing a nanozyme-based aptasensor for detection of small targets. • Various recent strategies and potential solutions to address these challenges are discussed. • Insights gained from past failures are highlighted to guide and refine future research in nanozyme-based aptasensing.