Enhanced Chemiluminescence under the Nanoconfinement of Covalent-Organic Frameworks and Its Application in Sensitive Detection of Cancer Biomarkers

Chemiluminescence (CL) with intensive emission has beenpursuedfor decades. It is still challenging to find a new mechanism to enhanceCL. In this work, confinement-enhanced CL was developed for the firsttime by the coembedding of N-(aminobutyl)-N-(ethylisoluminol) (ABEI)and Co2+ into gold nanoparticle-modified covalent-organicframeworks (COFs). For the consideration of improving the hydrophilicityof COFs and facilitating subsequent biological modification, goldnanoparticles were first reduced on the COF surface (Au-COF) in situwithout other reducing reagents. By virtue of the abundant imine bondand pi backbones, ABEI and Co2+ were embedded in Au-COFsynergistically through pi-pi stacking and coordination.The confinement of ABEI and Co2+ into Au-COF brought anover 20-fold enhancement of CL intensity compared to that of addingthem to a liquid phase, which benefitted from the three aspects ofthe confinement effect, including the molecular enrichment effect,the physical constraint effect, and the molecular preorganizationeffect. As proof of concept, a lipid-protein dual-recognitionsandwich strategy based on this CL-functionalized COF was developedfor the detection of breast cancer cell line-derived extracellularvesicles (EVs) with four orders of magnitude improvement in the detectionlimit compared to ELISA. The successful distinction of human epidermalgrowth factor receptor 2 (HER2)-positive patients from HER2-negativepatients indicated the great application potential of the proposedbioassay in HER2-positive breast cancer diagnosis. This work proposeda novel enhancement mechanism for CL based on crystalline porous materials,which provides a new perspective for the development of CL-functionalizedmaterials for biosensors and bioassays.

Automated summary

In this study, a new mechanism for enhancing chemiluminescence (CL) was developed through the coembedding of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) and Co2+ into gold nanoparticle-modified covalent-organic frameworks (COFs). The confinement of ABEI and Co2+ into Au-COF brought over 20-fold enhancement of CL intensity. This work proposes a novel enhancement mechanism for CL based on crystalline porous materials, which provides a new perspective for the development of CL-functionalized materials for biosensors and bioassays.