Drug targeting: learning from toxin entry and trafficking in mammalian cells.
A significant number of therapeutic targets reside inside cells and intracellular organelles. Therapeutics therefore must be able to gain access to cellular compartments, and be able to interact specifically with a given molecule to exert a desired effect. Many naturally occurring toxins perform such targeting with apparent ease, making them excellent paradigms for the delivery of therapeutics to the cell interior. By studying the mechanisms of cell entry, trafficking and modes of toxicity of these model delivery vectors, researchers can decipher how cells transport both endogenous molecules and exogenously applied therapeutics inside cells. Perhaps more importantly, the exploitation of cell binding and trafficking motifs could allow a therapeutic to target specifically, traffic within and escape from cellular compartments; in addition, toxic domains can be used to disrupt cell function specifically for therapeutic purposes. This review provides an overview of recent developments in the understanding of toxin targeting and trafficking, and discusses how these developments could result in opportunities for the design of more specific and efficient systems for therapeutic targeting.
Spooner
Robert A
RA
Cardiff University, School of Biosciences, Museum Avenue, Cardiff, CF10 3AX, UK. R.A.Spooner@warwick.ac.uk
Watson
Peter
P
D000818:Animals; D002477:Cells / Q000378:metabolism* / Q000648:ultrastructure; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles; D010949:Plasma / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D054852:Small Molecule Libraries; D014118:Toxins, Biological / Q000378:metabolism*
D054852:Small Molecule Libraries; D014118:Toxins, Biological