A molecular beacon-assisted nanotheranostic agent for real-time detection and effective combined management of acquired resistance to EGFR-TKIs

Abstract

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitably developed in non-small cell lung cancer (NSCLC) and the major cause of resistance to first-generation EGFR-TKIs is the T790M secondary mutation. Real-time detection of the acquired T790M mutation to avoid futile treatment and timely adjust the therapeutic interventions remains a great challenge. Molecular beacon (MB) could achieve real-time detection of point mutation and the fluorophores located at the terminal of MB could be activated for photodynamic therapy (PDT). Herein, a multifunctional nanoplatform CQEM based on erlotinib and tertiary amine dual-fabricated chitosan (CQE) loaded with cyanine dyes-labeled MB was prepared for simultaneous detection of the degree of T790M mutation in real-time and reversal of the resistance by PDT. CQE could protect MB against DNase I digestion and CQEM could achieve real-time sensing of T790M mutation during the course of EGFR-TKI treatments. With 808 nm laser irradiation, CQEM showed substantial therapeutic efficiency and could overcome the acquired resistance by the synergism of targeted molecular therapy and dual-cyanine dyes-mediated PDT. Thus, the CQEM nanoplatform could be an auspicious tool for individualized accurate therapy of NSCLC by real-time detection and management of the efficacy of EGFR-TKIs.