Ultra-Sensitive SERS And Fluorescence Dual-Mode Detection Of Tumor Active Substances And Circulating Tumor Cells (CTCs) Based On Multifunctional Nanomaterials

Although FDA-approved biomarker detection tools are already in clinical practice detection of biomarkers of extremely low abundance remains a challenge.For instance,circulating tumor cells can be as rare as 1 per 10~6～10~7 leukocytes,so the biomarkers vitally important as surrogates.The ability to identify disease biomarkers significantly improves diagnosis and monitoring as well as evaluation of the relevant therapeutic strategies.The key challenge in diagnosis is to identify multiple,low-abundance biomarkers in complex biological samples.Therefore,new technologies need to be developed for the detection of tumor markers.1.A dual-selective recognition and multi-enhanced surface enhanced Raman scattering(SERS)-fluorescence dual mode detection platform is designed for the detection of circulating tumor cells(CTCs).The gold nanoflowers(AuNFs)substrate was synthesized and the CTCs were captured on the surface area of AuNFs/ITO substrate by aptamers modified.At the same time,the novel nanoprobe was designed,anti-Ep CAM(AE)and trigger DNA were modified onto the surface of gold nanostars(AuNSs)through a PEG linker.The novel nanoprobe identified CTCs through the specific recognition reaction between AE and the cell epithelial adhesion molecule of the CTCs.The dual-recognition cellular mechanism of the aptamers and AE improves selectivity.Then,the complementary sequence(CS)hybridize with aptamers to release the captured CTCs into the culture medium.The number of CTCs released was detected by SERS and fluorescence.The limit of SERS detection was 5 cells/m L with a linear relationship from 5 to 200 cells/m L.The limit of fluorescence detection was 10cells/m L with a linear relationship from 10 to 200 cells/m L.Thus,the developed CTCs detection platform demonstrates promising applications for clinical diagnosis.2.The modular nature of metal-organic frameworks(MOFs)permits their tunable structure and function for target application,such as in biomedicine.Herein,a green-emission Zr(IV)-MOF(BUT-88)was constructed from a customized luminescent carbazolyl ligand.BUT-88 represents the first bcu-type MOF with both organic linker and metal node in eight connections and shows medium-sized pores,rich accessible linking sites,and good water stability and biocompatibility.In virtue of these merits,BUT-88 was then fabricated into a MOF-based fluorescent nanoprobe,dl DNA-BUT-88.Using it,the live-cell imaging of ATP was achieved for the first time upon a MOF-based probe,offering enhanced detection precision in early cancer diagnosis.Particularly,the probe showed efficient ratiometric fluorescent sensing toward the cytoplasmic biomarker ATP,further improving the detection accuracy at the cellular level.In this work,the elaborate combination of MOF engineering and the fluorescent detection technique has contributed a facile biosensing platform,unlocking more possibilities of MOF chemistry.3.Exosome act as a communicator between cells,which can transfer and deliver information about the original cells and exist in various body fluids.Exosomes are considered to be ideal candidates for early cancer diagnosis and evaluation of therapeutic efficacy due to the high abundance and stability.However,the highly expressed proteins on the surface of exosomes are usually associated with a variety of cancers,and it is difficult to distinguish them by a single marker.Herein,it is the first time to use the AuNRs arrays as SERS sensors,and realize the specific detection of exosomes secreted by SK-Br-3 cells.The gold nanorods are uniformly arranged in a hexagonal shape and the dense“hot spots”produces“hot surfaces”,which greatly improve the sensitivity and uniformity of detection.In presence of target exosomes,the DNA co-localization three-signal input switch causes the SERS signal increase,thereby realizing the specific detection of exosomes.This sensing strategy achieves a wide detection range(1.0×10~4～5.0×10~6 particles/m L)and a lower detection limit(5.3×10~3 particles/m L),without using any signal amplification mechanism.The sensor is expected to be widely used in the early diagnosis and treatment of cancer.