Potential of Surface Enhanced Raman Spectroscopy (SERS) in Therapeutic Drug Monitoring (TDM). A Critical Review

Abstract

Surface-Enhanced Raman Spectroscopy (SERS) is a label-free technique that enables quick monitoring of substances at low concentrations in biological matrices. These advantages make it an attractive tool for the development of point-of-care tests suitable for Therapeutic Drug Monitoring (TDM) of drugs with a narrow therapeutic window, such as chemotherapeutic drugs, immunosuppressants, and various anticonvulsants. In this article, the current applications of SERS in the field of TDM for cancer therapy are discussed in detail and illustrated according to the different strategies and substrates. In particular, future perspectives are provided and special concerns regarding the standardization of self-assembly methods and nanofabrication procedures, quality assurance, and technology readiness are critically evaluated.

Keywords: Individualized cancer chemotherapy; SERS; TDM; drug monitoring.

Figure 1

Schematic diagram of the flow cell used for quantitative analysis of mitoxantrone in clinical serum samples, adapted from [45].

Figure 2

(Left) Raman of solid MTX (A) and SERS (B–D) spectra of MTX (10 µM) in PBS solution (B), PBS-HSA solution (C), and diluted human serum (D). Light gray lines represent the background SERS signal due to the substrate itself; (Right) diagnostic plots from repeated double cross-validation (RDCV) of SERS data collected from PBS-HSA solutions (A) and diluted human serum (B). Reprinted with permission from [54].

Figure 3

Illustration of the structure of a SERS-active needle and the SERS detection of a depth profile based on the SERS-active needle. Reprinted with permission from [69].

Figure 4

Roadmap for the clinical translation of SERS for TDM. The well-known technology readiness levels (TRL) reached by the SERS works reported in this review are indicated with a color intensity scale: only the first 5 levels are covered. The majority of studies are at the “proof of principle” level or the “validation of single functionality” level (TRL 3–TRL4).