Percutaneous fiber-optic biosensor for immediate evaluation of chemotherapy efficacy in vivo (Part I): Strategy of assay design for monitoring non-homogeneously distributed biomarkers

Abstract

A fiber-optic apoptosis sensor is under development for the early assessment of tumor response to chemotherapy. It is aimed to provide bedside assessment during drug administration in differentiating treatment responses much earlier than conventional anatomical imaging techniques in tailoring the drug dosage for optimal treatment efficacy within a small therapeutic concentration window. Two fluorophores are embedded in the system for monitoring the non-homogeneously distributed apoptotic biomarker, the externalization of phosphatidylserine (PS). This manuscript introduces design concept of the 2-fluorophore assay, and summarizes the selection criteria of the 2 fluorophores, then identified the optimal exogenous fluorophores for the proposed fiber-optic apoptosis sensor from in vitro cell culture studies. FM 1-43 is the superior early apoptotic activity reporter for the in vivo monitoring fiber-optic sensor compared with the more widely commercialized annexin V-FITC, because it can provide superior sensitivity and specificity for the fiber-optic measurements with capability in potential needs of sequential detections. As a cell spatial distribution indicator (for calibrating the geometrical effect of the non-homogeneously distributed biomarkers on the detected fluorescent signal), phospholipid conjugated marina blue can provide timely quantifiable values indicating only cell densities (spatial distribution index), regardless of the treatment of the apoptotic initiator, without interfering the optical characteristics of FM 1-43 in indicating apoptotic activity. The bioanalytical performance of the sensor in identifying drug-induced apoptosis with the 2-fluorophore assay is assessed (in vitro and in vivo) in another manuscript (for further details see [19]).