A Versatile Tumor Microenvironment-Responsive Nanoprobe for Cancer Screening and Early Detection

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Early cancer detection remains a significant challenge, especially for small, millimeter-sized tumors.
• Current diagnostic methods often lack the sensitivity or specificity for timely cancer identification.

Purpose of the Study:

• To develop a tumor microenvironment (TME)-responsive nanoprobe for early cancer detection.
• To enable cross-validated cancer diagnosis using in vivo near-infrared fluorescence imaging and in vitro colorimetric urinalysis.

Main Methods:

• A multifunctional nanoprobe (PR-KAd@CD-AuNC) was designed, integrating a signal-output segment (CD-AuNC), a tumor-targeting component (PR), and a cleavable linker (KAd).
• The nanoprobe utilizes TME-specific matrix metalloproteinase-2 (MMP2) cleavage for size-dependent renal excretion and signal generation.
• In vivo imaging employed second near-infrared (NIR-II) fluorescence, while in vitro analysis used colorimetric detection in urine.

Main Results:

• The nanoprobe selectively accumulated in tumors via αvβ3 integrin targeting (PR component).
• NIR-II imaging provided high-resolution tumor delineation, while MMP2 cleavage released smaller CD-AuNC fragments for renal excretion.
• CD-AuNC fragments in urine produced a colorimetric signal, enabling a simple, low-cost screening method.
• The dual-modality approach demonstrated superior sensitivity to CT imaging for detecting small tumors across multiple cancer types.
• The strategy also proved effective in monitoring cancer therapeutic efficacy.

Conclusions:

• The developed nanoprobe offers a promising dual-modality strategy for sensitive and early cancer detection.
• This approach surpasses existing imaging techniques in sensitivity and provides a convenient method for monitoring treatment response.
• The findings suggest significant clinical potential for guiding cancer diagnosis and therapeutic decisions.