Real-Time Label-Free Monitoring of Drug- or Nanoparticle-Cell Interactions

Efficient drug delivery is one of the major challenges in modern pharmaceutical research. There is a constant need for developing new formulation strategies for new drug delivery systems because new chemical entities tend to have low solubility, and biotechnology drugs (e.g., DNA, oligonucleotides, antibodies, and proteins) permeate poorly to the target sites, limiting or even prohibiting their therapeutic use. The potency of new drugs is usually demonstrated by cell interaction tests (uptake, response, and toxicity). However, in vitro cell culture methods are not able to measure real-time kinetics of the cellular interaction processes,and they rely on labeled materials as well as on secondary detection techniques. Thus, there is an ever-increasing interest to develop new methodologies enabling real-time, noninvasive, label-free, and continuous high-sensitivity monitoring of drug-cell or nanoparticle (NP)-cell interactions that would provide complementary information to traditional in vitro cell culture methods. In this article, we present a summary of several experimental approaches our research group has taken in utilizing two physicochemical techniques, namely, surface plasmon resonance (SPR) and quartz crystal microbalances (QCM), to develop new methodologies for real-time label-free monitoring of drug or NP interactions with cell model layers and living cell monolayers.