Strategies and Progress of Raman Technologies for Cellular Uptake Analysis of the Drug Delivery Systems

Nanoparticle (NP)-based drug delivery systems have the potential to significantly enhance the pharmacological and therapeutic properties of drugs. These systems enhance the bioavailability and biocompatibility of pharmaceutical agents via enabling targeted delivery to specific tissues or organs. However, the efficacy and safety of these systems are largely dependent on the cellular uptake and intracellular transport of NPs. Thus, it is crucial to monitor the intracellular behavior of NPs within a single cell. Yet, it is challenging due to the complexity and size of the cell. Recently, the development of the Raman instrumentation offers a versatile tool to allow noninvasive cellular measurements. The primary objective of this review is to highlight the most recent advancements in Raman techniques (spontaneous Raman scattering, bioorthogonal Raman scattering, coherence Raman scattering, and surface-enhanced Raman scattering) when it comes to assessing the internalization of NP-based drug delivery systems and their subsequent movement within cells.