Integration of Nanotechnology with ctDNA: New Advances for Monitoring Neoadjuvant Chemotherapy

The evaluation of tumor response in the neoadjuvant chemotherapy (NACT) is still difficult as traditional imaging techniques can only provide morphological information at discrete intervals, and pathological response is usually assessed only after surgery. Although circulating tumor DNA (ctDNA) has the potential to provide a minimally invasive approach to monitor molecular response during treatment, its clinical use is hampered by low presence, high fragmentation, rapid clearance and the presence of high levels of non-tumor cell-free DNA (cfDNA). In this review, we aim to discuss the challenges of ctDNA detection in analytical and biological settings and how nanotechnology may be able to help address these challenges, particularly during the NACT window. The analytical performance and the potential integration of nanotechnology platforms, including gold nanoparticle plasmonic sensing, magnetic nanoparticle (MNP) extraction and microfluidic integration, fluorescent quantum dots for multiplexing, carbon-based electrochemical sensors and nano‑based CRISPR biosensing, enable a rapid detection of ctDNA. Benefits of these nanotechnological platforms are not just that technologies exist, but that early ctDNA clearance predicts response, persistence signals resistance, and nanotechnology makes routine, sensitive, and rapid monitoring feasible, provided certain translational hurdles are cleared. While there is great promise for the use of nanotechnology to enable fast, sensitive detection of ctDNA during NACT, significant issues remain in standardization of assays, reproducible manufacturing, prospective validation, and cost-effectiveness before clinical use is a reality.