Programming Thermoresponsiveness of NanoVelcro Substrates Enables Effective Purification of Circulating Tumor Cells in Lung Cancer Patients

TLDR

Circulating tumor cells serve as a liquid biopsy that overcomes sampling bias of solid biopsies and can provide prognostic and molecular insights across all disease sites. The authors aimed to create a Thermoresponsive NanoVelcro system that can be digitally programmed for optimal purification of CTCs from non‑small cell lung cancer patients. They optimized the platform by systematically adjusting surface chemistry, flow rates, and heating/cooling cycles within a mild 4–37 °C range to preserve CTC viability and molecular integrity. The system enabled successful culture expansion, mutational analysis, and longitudinal monitoring of disease evolution in an NSCLC patient, demonstrating its translational potential.

Abstract

Unlike tumor biopsies that can be constrained by problems such as sampling bias, circulating tumor cells (CTCs) are regarded as the "liquid biopsy" of the tumor, providing convenient access to all disease sites, including primary tumor and fatal metastases. Although enumerating CTCs is of prognostic significance in solid tumors, it is conceivable that performing molecular and functional analyses on CTCs will reveal much significant insight into tumor biology to guide proper therapeutic intervention. We developed the Thermoresponsive NanoVelcro CTC purification system that can be digitally programmed to achieve an optimal performance for purifying CTCs from non-small cell lung cancer (NSCLC) patients. The performance of this unique CTC purification system was optimized by systematically modulating surface chemistry, flow rates, and heating/cooling cycles. By applying a physiologically endurable stimulation (i.e., temperature between 4 and 37 °C), the mild operational parameters allow minimum disruption to CTCs' viability and molecular integrity. Subsequently, we were able to successfully demonstrate culture expansion and mutational analysis of the CTCs purified by this CTC purification system. Most excitingly, we adopted the combined use of the Thermoresponsive NanoVelcro system with downstream mutational analysis to monitor the disease evolution of an index NSCLC patient, highlighting its translational value in managing NSCLC.