The goal of targeted therapeutics and molecular diagnostics is to accumulate drugs or probes at the site of disease in higher quantities relative to other locations in the body. We envisioned a targeting strategy that would lead to an active accumulation of nanoparticles by virtue of an assembly event specific to endogenous, enzymatic biochemical signals associated with tumor tissue. We reasoned that the best signal for this purpose would come from the catalytic activity specific to matrix metalloproteinases, MMP-2 and MMP-9, known to be overexpressed in certain tumor types. We demonstrate the viability of this approach through a proof-of-concept study showing enzyme-directed particle targeting and accumulation in human xenograft tumors in mice following intravenous injection, and demonstrate retention of particles within tumors for extended periods of time. In contrast to the conventional passive approach, enhanced permeability retention (EPR) effect, the problem of short retention of small molecules (drugs/probes) inside of the targeted tissues can be therefore overcome. Herein, we propose a novel method to program the pharmacokinetics in vivo via manipulation of morphology switch of nanoparticles in response to specific cancer-associated signal and illuminate the potential application of alternative drug release mechanism from the morphology switching nanomaterials.

Nanoparticles targeted, accumulated, and retained in tumors via an enzyme-programmed morphology switch

245th National Meeting (2013)

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