| Herein we describe the fabrication of red blood cell (RBC)-encapsulated optodes for the imaging of lithium levels in the blood for drug monitoring purposes. Lithium monitoring is important for tracking minute changes in lithium levels that can lead to toxicity or ineffectiveness due to lithium's narrow therapeutic window. The monitoring component that can detect these changes, optodes, are optical sensors that are ion-selective and change fluorescence respective to changing ion concentration. An RBC membrane coating is used to create a biomimetic surface that encapsulates lithium optodes to camouflage the sensing components as a biologic and evade cellular uptake or filtration. Thus, enabling sensors to circulate through the body for an extended period time while cloaked in RBCs and continuously monitor changes in lithium concentration as it is metabolized in the body. Purified RBC membrane fragments are used to encapsulate lithium optodes into both nanosensors and microparticles. The effect of size and presence of polymer within the nanosensors and microparticles is explored. The nanosensors showed lithium selectivity over physiological levels of sodium and concentration sensitivity over the physiological range of lithium. These nanosensors were too small to be seen under an external in vivo fluorescent imaging system fabricated in a collaborating lab and, thus, microparticles were made. The size of the microparticles also enabled them to better mimic an RBC morphologically. Microparticles showed responsiveness to lithium concentration changes via ratiometric fluorescent measurements over the physiological range but had less sensitivity when compared to the nanosensors. The microparticles were also studied with a surface moiety on the RBC coating. Overall, this study has created a platform in which many different ion detecting optodes can be incorporated into RBCs for camouflaged and extended drug monitoring in the blood. |
