Recent advances in isothermal amplification-integrated nanomaterial-based biosensing platforms for sensitive detection of cancer-related nucleic acids
TL;DR
A unified framework for understanding the design principles and functional integration of INAA-based biosensing platforms is provided, offering insights to guide future innovation in ultrasensitive nucleic acid detection.
Abstract
The detection of cancer-associated nucleic acid biomarkers, including circulating tumor DNA and non-coding RNAs, remains a major analytical challenge due to their extremely low abundance in biological fluids, particularly at early disease stages. Isothermal nucleic acid amplification (INAA) has emerged as a powerful alternative to conventional PCR-based methods, enabling sensitive target amplification under constant temperature conditions while reducing instrumentation complexity. In parallel, the integration of nanomaterials into biosensing platforms has provided versatile interfaces for signal transduction, amplification, and probe immobilization. This review presents a comprehensive and structured overview of recent advances (2020–2025) in biosensing platforms combining INAA strategies with nanomaterial-enabled functionalities for cancer-related nucleic acid detection. We first examine the fundamental principles and mechanistic diversity of major INAA approaches, including enzyme-assisted (LAMP, RCA, RPA, SDA, EXPAR) and enzyme-free systems (HCR, CHA), highlighting their respective advantages and limitations. We then critically discuss their integration into biosensing architectures, emphasizing how nanomaterials enhance analytical performance through improved surface engineering, catalytic activity, and signal generation. Emerging hybrid platforms incorporating CRISPR/Cas systems, lateral flow assays, microfluidics, DNAzyme catalysis, and smartphone-assisted readouts are further analyzed, demonstrating significant progress toward highly sensitive, portable, and multiplexed diagnostic systems. Finally, current challenges related to assay robustness, standardization, and clinical translation are addressed, along with future perspectives for the development of next-generation point-of-care cancer diagnostics. This review provides a unified framework for understanding the design principles and functional integration of INAA-based biosensing platforms, offering insights to guide future innovation in ultrasensitive nucleic acid detection.