Reversible and Highly Ordered Biointerfaces for Efficient Capture and Nondestructive Release of Circulating Tumor Cells

Abstract

The engineering strategy of artificial biointerfaces is vital for governing their performances in bioanalysis and diagnosis. Highly ordered arrangement of affinity ligands on the interface surface facilitates efficient interaction with target molecules, whereas biointerfaces aimed at drug delivery or rare cell isolation require sophisticated stimuli-response mechanisms. However, it is still challenging to facilely fabricate biointerfaces possessing the two features. Herein, we endow a biointerface with both reversibility and capability to orderly assemble affinity ligands by introducing boronic acid moieties alone. By boronate conjugation via glycosylation sites, avidin was well arranged at the surface of boronic acid-decorated carbon nitride nanosheets for the assembly of biotinylated aptamers. The ordered orientation of aptamers largely relieved their inactivation caused by inter-strand entanglement, facilitating significant increase in cell affinity for the isolation of circulating tumor cells (CTCs). The reversible boronate conjugation also facilitated mild release of CTCs by acid fructose with high cell viability. This engineered interface was capable of isolating CTCs from the peripheral blood of tumor-bearing mice and cancer patients. The successful utilization of the isolated CTCs in the downstream drug susceptibility test and mutation analysis demonstrated the clinical potential of this biointerface for the early diagnosis of cancers and precision medicine.

Programmable DNA Circuit-Facilitated Determination of Circulating Extracellular Vesicle PD-L1 for Lung Cancer Diagnosis and Immunotherapy Response Prediction

“…Then, two DNA probes are employed to label the enriched EVs. One is the aptamer probe AP that contains an aptamer motif to recognize PD-L1 29 and an activation motif (a) to trigger the downstream DNA circuit; another one is the PBA-b, which reversibly binds glycoprotein 30 expressed on the EV membrane and acts as an assistant probe to reflect the expression of EV PD-L1. As shown in Scheme 1B, after the labeling of enriched EVs, a programmable DNA circuit is conducted at the biomembrane interface with the use of two DNA probes, a1/b1 and c/d.…”

Recent progress of nanostructure-based enrichment of circulating tumor cells and downstream analysis

“…8E). 119 Compared with the free aptamer, the affinity of the engineered cell capture interface to the target CTCs is 100 times higher, and the captured CTCs can be released competitively through high-activity acidic fructose, which is beneficial to downstream cell culture and genome analysis, and further used for drug sensitivity test.…”

Biosensors with Boronic Acid-Based Materials as the Recognition Elements and Signal Labels

“…Meanwhile, phosphorylated sites could interact with the metal node Zr(IV) of UIO-66-NH 2 to interrupt the metal-ligand charge transfer, also restoring the fluorescence. To lower the pKa value and stabilize the boronic esters in neutral pH media, Wulff-type boronic acid derivatives consisting of an amine adjacent to the boric group were employed to modify the fluorescent nanomaterials [ 159 ]. g-C 3 N 4 nanosheets have intrinsic N atoms in both the backbone and edges.…”