SERS hydrogel designed using a microfluidic droplet platform for label-free therapeutic drug monitoring of doxorubicin in human serum.

in Analytica chimica acta by Ying Wang, Jinru Cao, Ziwei Xu, Yaqin Zhan, Ziyu Xu, Hao Cheng, Wenyi Huang, Hongxing Kong, Jun Feng

TLDR

  • A novel method for rapid, sensitive, and reproducible detection of Doxorubicin (DOX) in human serum using surface-enhanced Raman spectroscopy (SERS) substrates was developed.

Abstract

Doxorubicin (DOX) is an anthracycline anticancer drug that is commonly employed in the treatment of acute leukemia, malignant lymphoma, breast cancer and prostate cancer. Given the narrow safe dosage range and the strong toxic reaction associated with the drug, prolonged or excessive use can result in serious adverse reactions, which greatly limits its clinical application. It is therefore necessary to develop a rapid, sensitive and reproducible therapeutic drug monitoring (TDM) method for DOX in order to create an individualised dosing regimen based on the patient's specific situation, thus facilitating the precise treatment of the disease. We prepared hydrogel microspheres encapsulated with AgNPs as SERS substrates on a microfluidic droplet platform, utilising PEGDA as the monomer. The hydrogel microspheres have a 3D mesh structure with adjustable pore size, which facilitates the uniform dispersion of AgNPs in the hydrogel particles. This not only safeguards AgNPs from the biological matrix and enhances their stability and SERS signal reproducibility, but also facilitates the formation of denser SERS "hotspots" for highly sensitive SERS detection. Concurrently, the pore size of the hydrogel microspheres can preclude the interference of biomacromolecules in the biological matrix, thereby enabling the selective facilitation of the entry of small molecules. The selective, label-free SERS detection of DOX within human serum was successfully achieved by employing AgNPs@microgel SERS substrates. The linearity of DOX was demonstrated within the concentration range of 1.0-10ng mL, with a detection limit of 1.0 ng mL. The method is characterised by its rapidity, sensitivity, reproducibility, the absence of any sample pretreatment requirements and minimal sample consumption. As a consequence, it provides a new avenue for the highly sensitive and reproducible label-free detection of DOX in human serum. Meanwhile, the new method has the potential to detect more small molecule drugs, which has a broad application potential in clinical TDM.

Overview

  • The study focuses on developing a rapid, sensitive, and reproducible therapeutic drug monitoring (TDM) method for Doxorubicin (DOX) using surface-enhanced Raman spectroscopy (SERS) substrates.
  • The method involves preparing hydrogel microspheres encapsulated with silver nanoparticles (AgNPs) as SERS substrates on a microfluidic droplet platform.
  • The primary objective is to create an individualized dosing regimen for DOX based on the patient's specific situation, facilitating precise treatment of the disease.

Comparative Analysis & Findings

  • The method demonstrated linearity for DOX detection within the concentration range of 1.0-10 ng/mL, with a detection limit of 1.0 ng/mL.
  • The method is characterized by its rapidity, sensitivity, reproducibility, absence of sample pretreatment requirements, and minimal sample consumption.
  • The results show the successful selective, label-free SERS detection of DOX within human serum using AgNPs@microgel SERS substrates.

Implications and Future Directions

  • The method has significant potential for clinical TDM and can be applied to detect more small molecule drugs.
  • Future research directions could involve exploring the use of this method for monitoring other anticancer drugs and optimizing the design of SERS substrates.
  • The development of this method can contribute to personalized cancer treatment and improve patient outcomes, as it allows for individualized dosing regimens based on a patient's specific situation.