Chemotherapy has been the leading therapy for treating cancer to date. However, its applicability has been limited by high price and low effectiveness of current chemotherapeutics. The limitations could be overcome by understanding the therapeutic mechanism of drug candidates allowing the best compounds to undergo expensive and time-consuming clinical trials. Although cell-based profiling methods greatly streamline the drug screening process, the current methods are restricted by multistep processing, time consuming and low-throughput analysis, and the requirement of large number of cells. The FunStar Capsule proposal aims to develop a simple and powerful supramolecular nanocapsule platform for phenotyping drug-treated cell surfaces. This radically new concept in drug screening will generate characteristic spectroscopic patterns for different drug-treated cell surfaces that will be used to predict the mechanisms of new therapeutic molecules. The proposal introduces for the first time live cell Raman micro-spectroscopy for creating the patterns using a unique nanocapsule that is fabricated through the hierarchical assembly of functionalized gold nanoparticles (AuNPs) and nanostars. The AuNPs will recognize the cell membrane while the nanostars will create characteristic Raman signatures through a surface enhanced Raman scattering mechanism. The robust and biocompatible platform would provide several advantages: (i) rapid (minutes) analysis, (ii) less number of cells required (possibly single cell), (iii) label-free method, (iv) highly sensitive and non-destructive technique, (v) both efficacy and mechanism of a molecule can be determined from a single well of a microplate. This multidisciplinary proposal combines concepts of materials chemistry and life sciences to design a cell phenotyping platform with applications beyond drug screening such as cancer detection and cell sorting, making this approach attractive for industrial sectors of pharmacology and diagnostics.
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