Abstract: The present invention provides methods and compositions for highly precise spatial and temporal control over cytosolic delivery of compounds, in particular, those compounds that would otherwise be cell-impermeable. Among other things, the present invention provides a composition for targeted drug delivery comprising a nanoparticle, a targeting moiety specific for a cell type of interest, a light-activated drug delivery system, wherein the nanoparticles are associated with the targeting moiety and the light-activated drug delivery system.

Abstract: The invention provides nanosensors and nanosensor components for the detection of ion channel activity, receptor activity, or protein protein interactions. Certain of the nanosensor components comprise a nanoparticle and recognition domain. Following contact with cells and, optionally, internalization of the nanosensor component by a cell, the recognition domain binds to a target domain, e.g., a heterologous target domain, of a polypeptide of interest such as an ion channel subunit, G protein coupled receptor (GPCR), or G protein subunit. Ion channel activity, GPCR activity, or altered protein interaction results in a detectable signal. The nanoparticles may be functionalized so that they respond to the presence of an ion by altering their proximity. Certain of the nanosensors utilize the phenomenon of plasmon resonance to produce a signal while others utilize magnetic properties, RET, and/or ion-sensitive moieties. Also provided are polypeptides, e.g.