More than a decade into the development of gold nanoparticles for cancer therapies, with multiple clinical trials underway, ongoing pre-clinical research continues towards better understanding in vivo interactions with the goal of treatment optimization through improved best practices. In an effort to collect information for healthcare providers, enabling informed decisions in a relevant time frame, instrumentation for real-time plasma concentration (multi-wavelength pulse photometry) and protocols for rapid elemental analysis (energy dispersive X-Ray fluorescence) of biopsied tumor tissue have been developed in a murine model. An initial analysis, designed to demonstrate the robust nature and utility of the techniques, revealed that area under the bioavailability curve (AUC) alone does not currently inform tumor accumulation with a high degree of accuracy (R2=0.32), This finding suggests that the control of additional experimental and physiological variables may yield more predictable tumor accumulation. Subject core temperature are blood pressure were monitored, but did not demonstrate clear trends. An effort to modulate AUC has produced an adjuvant therapy which is employed to enhance circulation parameters, including the AUC, of nanorods and gold nanoshells. Preliminary studies demonstrated a greater than 300% increase in average AUC through the use of a reticuloendothelial blockade agent versus control groups. Given a better understanding of the relative importance of the physiological factors which impact rates of tumor accumulation, a proposed set of experimental best practices is presented.
A novel multi-wavelength photoplethysmograph (PPG), previously utilized to quantify optically absorptive circulating gold nanoparticles, has demonstrated the potential to enhance therapeutic treatment predictability as pharmacokinetic metrics are provided throughout the intravenous delivery phase of quinine in real-time. This report demonstrates how the PPG could be used to assess the real-time bioavailability of other types of intravenously delivered optically-absorbing nanoparticles and drugs. The drug currently under investigation is anti-malarial quinine (absorption peak ~350 nm). We describe how the algorithm has been adapted to quantify the concentration of quinine in the pulsatile, circulating blood based on its extinction at three wavelengths (340, 660 and 940 nm). We show an example of the system collecting data representing the baseline, injection, and the clearance phases. An examination of the raw signal suggests that the system is well suited to sense the concentration of quinine in the therapeutic range (10mg/kg).