Photoexcitation-based nano-explorers: Chemical analysis inside live cells and photodynamic therapy

PEBBLEs (Probes Encapsulated By Biologically Localized Embedding) are submicron-sized optical sensors designed specifically for minimally invasive analyte monitoring in viable single cells, with applications for real-time analysis of drug, toxin, and environmental effects on cell function. PEBBLE nanosensor is a general term that describes a family of matrices and nano-fabrication techniques used to miniaturize many existing optical sensing technologies. The main classes of PEBBLE nanosensors are based on matrices of cross-linked polyacrylamide, crosslinked poly(decyl methacrylate), and sol-gel silica. These matrices have been used to fabricate sensors for H+, Ca2+, K+, Na+, Mg2+, Zn2+, Cu2+, Cl-, O-2, NO, and glucose that range from 20 nm to 600 nm in diameter. A number of delivery techniques have been used successfully to deliver PEBBLE nanosensors into mouse oocytes, rat alveolar macrophages, rat C6-glioma, and human neuroblastoma cells. PEBBLEs with several newly emerging directions in design and applications, going from intracellular imaging to in vivo actuating and targeting, are also described. They include photonic, magnetic, and stochastic control and modulation of photo-excitation, and also targeted nano-platforms for photodynamic therapy of brain cancers, as well as contrast enhancement of the MRI for monitoring such therapy.