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<p>The emergence of targeted therapies against the epidermal growth factor receptor (EGFR) has transformed the treatment landscape for metastatic colorectal cancer (mCRC). However, the absence of methodologies capable of dynamically monitoring drug-target engagement and subsequent molecular responses at high sensitivity represents a critical translational gap, impeding personalized treatment adaptation. Here, we report an integrated nanoscale sensing platform that synergizes a high-quality-factor (high-<i>Q</i>) Terahertz (THz) metasensor with modularly engineered exosome-targeting theranostic probe (Exo-TTprobe) for ultrasensitive, longitudinal evaluation of targeted therapy efficacy. By exploiting exosomes as natural nanocarriers of membrane-bound drug-target complexes, our system achieves specific detection through a dual amplification strategy combining rolling circle amplification (RCA) and gold nanoparticle-enhanced THz transmission shifts. The platform exhibits exceptional sensitivity with a detection limit of 10<sup>3</sup> particles/ml across a dynamic range spanning 10<sup>3</sup> to 10<sup>8</sup> particles/ml, enabling discrimination of heterogeneous EGFR expression and drug response in cetuximab-sensitive and non-sensitive CRC cell lines within hours of cetuximab exposure. Most notably, in a clinical cohort of 15 mCRC patients, we successfully captured therapy-specific molecular signatures directly from plasma-derived exosomes, identifying statistically significant differential signals within 12&#xa0;h of targeted therapy, which further intensified by 24&#xa0;h. Compared to traditional imaging evaluation, our method has the potential for early assessment of targeted therapy and adaptation to precision medicine. This work establishes a transformative paradigm for real-time, molecular-level monitoring of targeted therapeutics, with broad potential applicability across diverse oncogenic drivers and cancer types.</p>

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A dynamic theranostic platform: real-time tracking of targeted drug efficacy on exosomal membranes for metastatic colorectal cancer via terahertz metasensing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Yanan Jiao,
  • Zhaofu Ma,
  • Kang Zhao,
  • Qingzhe Jia,
  • Zeqiu Lao,
  • Guijun Zou,
  • Ding Zhao,
  • Zhaolong Xia,
  • Yuhong Wang,
  • Minghui Kong,
  • Min Qiu,
  • Xiaohui Du

摘要

The emergence of targeted therapies against the epidermal growth factor receptor (EGFR) has transformed the treatment landscape for metastatic colorectal cancer (mCRC). However, the absence of methodologies capable of dynamically monitoring drug-target engagement and subsequent molecular responses at high sensitivity represents a critical translational gap, impeding personalized treatment adaptation. Here, we report an integrated nanoscale sensing platform that synergizes a high-quality-factor (high-Q) Terahertz (THz) metasensor with modularly engineered exosome-targeting theranostic probe (Exo-TTprobe) for ultrasensitive, longitudinal evaluation of targeted therapy efficacy. By exploiting exosomes as natural nanocarriers of membrane-bound drug-target complexes, our system achieves specific detection through a dual amplification strategy combining rolling circle amplification (RCA) and gold nanoparticle-enhanced THz transmission shifts. The platform exhibits exceptional sensitivity with a detection limit of 103 particles/ml across a dynamic range spanning 103 to 108 particles/ml, enabling discrimination of heterogeneous EGFR expression and drug response in cetuximab-sensitive and non-sensitive CRC cell lines within hours of cetuximab exposure. Most notably, in a clinical cohort of 15 mCRC patients, we successfully captured therapy-specific molecular signatures directly from plasma-derived exosomes, identifying statistically significant differential signals within 12 h of targeted therapy, which further intensified by 24 h. Compared to traditional imaging evaluation, our method has the potential for early assessment of targeted therapy and adaptation to precision medicine. This work establishes a transformative paradigm for real-time, molecular-level monitoring of targeted therapeutics, with broad potential applicability across diverse oncogenic drivers and cancer types.