Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.
The nonspecific sorption of hydrophobic pharmaceuticals on reaction vessel surfaces raises serious analytical challenges for their accurate quantification. Systematic error due to sorptive loss of analytes may result in significant overestimation of drug loading on nanomaterial-based Drug Delivery Systems (DDS), leading to inaccurate determinations of dosage and DDS efficiency. We evaluated sorptive losses of doxorubicin (DOX), an effective chemotherapeutic, in polystyrene based 96-well plates, and proposed a simple but effective method to prevent the nonspecific sorption of DOX using trace concentrations of polyethylene glycol (PEG). Relative to widely used proteinaceous and surfactant surface blocking agents, PEG is effective, easy to use, and does not interfere with drug loading to the DDS.
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