Disintegrating Drug Deliverers

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Science  23 Nov 2001:
Vol. 294, Issue 5547, pp. 1619
DOI: 10.1126/science.294.5547.1619a

A biological cell uses a set of messengers, such as cyclic AMP, in order to transmit the detection of changes in its environment (registered at the cell surface) to intracellular compartments. One key participant is the cyclic AMP-dependent protein kinase (PKA), which phosphorylates residues on target proteins, causing changes in conformation and function.

Katayama et al. have developed a model system by taking a PKA substrate peptide and grafting it to a temperature-responsive polymer chain. When phosphorylated, the upper solubility temperature of the graft copolymer increases from 33°C to above 37°C, which is nominal body temperature. A third unit, when incorporated into the unphosphorylated copolymer, caused it to form micellar particles, which disintegrated on treatment with PKA. When these micelles were preloaded with a fluorescent dye and then incubated with PKA, a gradual release of the fluorescent molecules was observed. The authors envision that swapping the PKA-responsive peptide for one recognized by aberrantly expressed kinases may yield targeted drug delivery vehicles that would deliver their contents only to dysfunctional cells.—MSL

Macromolecules, 10.1021/ma010966a.

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