Preparation Of PVDF-loaded Ag Nanoflowers SERS Membrane And Its Application In Antitumor Drug Detection

Objective:Cancer is one of the leading causes of death worldwide.In the course of cancer treatment,the application of antitumor drugs is of great significance.General antitumor drugs kill cancer cells at the same time,but also have different degrees of damage to normal tissue cells,and have potential toxicity to human health.Therefore,it is necessary to provide a fast,convenient,cheap and efficient detection method for clinical drug concentration monitoring.At present,the detection methods of antitumor drugs have the disadvantages of complicated sample processing and long time.However,surface-enhanced Raman scattering spectroscopy（SERS）has the advantages of molecular fingerprint information,high sensitivity and narrow spectral bandwidth.In this study,silver nanoflower particles were synthesized by liquid phase reduction method,combined with polyvinylidene fluoride（PVDF）filter membrane as the SERS base,and the SERS base was optimized to improve the sensitivity,realizing highly sensitive detection and rapid analysis of anti-tumor drugs,providing a fast,convenient,inexpensive and efficient detection means for future clinical drug concentration monitoring.Method:Firstly,Silver nano-flower particles（Ag NFs）with high SERS activity and good stability were synthesized by liquid phase reduction method with silver nitrate（Ag NO₃）as precursor,ascorbic acid（AA）as reducing agent and polyvinylpyrrolidone（PVP）as surfactant.The morphology of silver nanoflowers was characterized by scanning electron microscopy and transmission electron microscopy.The optical capability was measured by UV-vis spectrophotometer and the purity of silver nanoflower was tested by X-ray diffractometer.The influence of PVP on SERS activity was further investigated,and silver nanoparticles with the best SERS substrate activity were selected to load on PVDF.Using the hydrophobic properties of PVDF combined with the rapid detection function of SERS technology,the flexible substrate membrane of Ag nanoflower and polyvinylidene fluoride（PVDF@Ag NFs）was prepared by loading Ag nanoflower on PVDF.Crystal violet（CV）was selected as SERS probe molecule to investigate the sensitivity,repeatability and stability of PVDF@Ag NFs basement membrane.The SERS enhanced effect was verified by FDTD simulation.Finally,the SERS of methadine,6-mercaptopurine,doxorubicin and fluorouracil in different concentrations of aqueous solution and serum were simulated by the addition method.Result:Silver nanoparticles with a diameter of 650～700 nm and a surface projection of50～70 nm were successfully prepared by liquid phase reduction synthesis.In addition,the high purity of these Ag NFs was confirmed by X-ray diffractometry（XRD）.The detection limit of CV by PVDF@Ag NFs substrate was 10-9 M,and the relative standard deviation（RSD）at 1175 and 1621cm^-1 was 8.58%and 5.50%,respectively.The result was much less than 20%,and the SERS activity was still maintained within 28 days under the same detection and storage conditions,indicating that the substrate membrane had good sensitivity,repeatability and stability.PVDF@Ag NFs substrate membrane detected aqueous solutions of DOX,MTX,6-MP and 5-FU at different concentrations,and found that the detection limit was as low as 0.1μg/m L.Finally,serum was treated by organic phase precipitation method to remove the interference of proteins,thereby improving the detection sensitivity of anti-tumor drugs in human serum.The results showed that the detection limit of antitumor drugs in serum was less than 1μg/m L.Conclusion:In this paper,the SERS base membrane of polyvinylidene fluoride（PVDF）composite was prepared for detecting antitumor drugs in human serum.Ag NFs was prepared by liquid phase reduction method.Due to the overlapping of their dense nanoscale petals,the surface protruded to form a"hot spot",which can generate a strong electromagnetic field.Furthermore,combined with PVDF hydrophobicity,its surface roughness further enhanced the SERS signal intensity.CV was used as a SERS probe molecule to investigate the SERS properties of PVDF@Ag NFs basement membrane,which showed high sensitivity,repeatability and stability.In addition,the detection of different concentrations of antitumor drugs showed a good linear correlation.The detection of antitumor drugs in simulated human serum was realized.In summary,this method provides a novel,cheap and simple clinical monitoring tool for SERS detection of various anti-tumor drugs,and provides a reference for future research on SERS in drug detection and other fields.