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APE1-Triggered Inhalable Microsphere (ATIM) for In Situ Non-Small Cell Lung Cancer Theranostics.

Xinlin Guo1, Xiaopei Qiu1, Xiaolin Hu1

  • 1Department of Laboratory Medicine, Chongqing Center for Clinical Laboratory, Chongqing Academy of Medical Sciences, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing, China.

Advanced Materials (Deerfield Beach, Fla.)
|April 29, 2026
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Summary
This summary is machine-generated.

A novel inhalable microsphere system (ATIM) precisely diagnoses and treats early-stage non-small cell lung cancer (NSCLC). This theranostic approach enhances tumor imaging and induces cancer cell apoptosis, improving early lung cancer management.

Keywords:
NSCLCape1exosomesin situ detectiontheranostics

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Accurate diagnosis of pulmonary nodules is crucial for effective non-small cell lung cancer (NSCLC) treatment.
  • Misdiagnosis can lead to delayed therapy or unnecessary invasive procedures.
  • Developing targeted theranostic systems is essential for improving early-stage NSCLC management.

Purpose of the Study:

  • To develop an apurinic/apyrimidinic endonuclease 1 (APE1)-triggered inhalable microsphere (ATIM) system for non-small cell lung cancer (NSCLC) theranostics.
  • To leverage inhalation delivery and homotypic targeting for enhanced pulmonary tumor accumulation.
  • To enable in situ NSCLC theranostics through fluorescence imaging and targeted therapy.

Main Methods:

  • Fabrication of APE1-triggered inhalable microspheres (ATIM) incorporating DNA tetrahedrons (TDNs).
  • Inhalation delivery of ATIM for targeted accumulation in pulmonary tumors.
  • Activation of entropy-driven catalytic circuits upon APE1 recognition for nanoparticle aggregation and fluorescence amplification.
  • Release of miR-126-3p to induce tumor cell apoptosis by suppressing ADAM9.

Main Results:

  • ATIM system demonstrated a 1.67-fold higher fluorescent intensity in tumor-bearing mice compared to healthy controls.
  • Pulmonary accumulation of ATIM via inhalation was 3.12-fold higher than via intravenous injection.
  • ATIM therapy significantly reduced tumor burden to a relative area of 45.3 ± 1.6% in a mouse orthotopic NSCLC model.

Conclusions:

  • ATIM system enables accurate discrimination between benign and malignant pulmonary nodules.
  • The system effectively induces apoptosis in non-small cell lung cancer cells.
  • ATIM offers a promising dual-functional platform for precision diagnosis and targeted therapy in early-stage NSCLC.