Proteolytic Actuation of Nanoparticle Self-Assembly

✍ Scribed by Todd J. Harris; Geoffrey von Maltzahn; Austin M. Derfus; Erkki Ruoslahti; Sangeeta N. Bhatia

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 435 KB
• Volume: 118
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/ange.200600259

✦ Synopsis

Nature has evolved elegant strategies to temporally and spatially control the initiation of protein activity, including the synthesis of subunits that self-assemble to form a functional unit and the synthesis of proteins with prodomains that require cleavage for activation. Nanomaterials that exploit bio-inspired self-assembling motifs have been used for sensitive detection of DNA, [1,2] proteins, [3,4] viruses, [5] and pH changes [6] in vitro. In general, these systems employ complementary chemistries that are constitutively exposed and lack elements of temporal control that could broaden their applicability. Herein, inspired by the biological motif of initiating assembly by enzymatic removal of inhibitors, we demonstrate with peptide-polymer chemistry that inorganic nanoparticles may be functionalized to exist in a "latent" state until triggered by a protease to self-assemble.

We inhibit the binding of biotin and neutravidin coated superparamagnetic Fe 3 O 4 nanoparticles with polyethylene glycol (PEG) polymers that may be proteolytically removed to initiate assembly by matrix metalloproteinase-2 (MMP-2), a protease correlated with cancer invasion, angiogenesis, and metastasis. [7][8][9] We demonstrate that MMP-2 initiated assembly amplifies the transverse (T2) relaxation of nanoparticle