Subcellular targeting: a new frontier for drug-loaded pharmaceutical nanocarriers and the concept of the magic bullet.

The ability of a pharmacologically active molecule selectively to find its target is closely linked with its potential as a successful therapeutic drug. It has become increasingly evident that there are several pharmacologically active molecules that exert their action on molecular targets inside cell organelles. In the case of a drug molecule with no defined specificity for a particular organelle, the molecule would either need to have sufficiently long metabolic stability to allow for random interaction with the organelle to occur, or a targeting strategy for the intended subcellular compartment would need to be devised in order to potentiate therapeutic effect. In the case of molecules with a stronger affinity for a non-target subcellular compartment, there exists even greater need for the ability to control subcellular disposition. Subcellular or organelle-specific targeting has thus emerged as a new frontier in drug delivery. In this review selected examples of recent work are discussed that the authors believe might eventually lead to the application of pharmaceutical nanocarriers to create the next generation of 'magic bullets' that are capable of delivering a drug payload to a molecular target at a subcellular location.