Enzyme-Directed Assembly of a Nanoparticle Probe in Tumor Tissue
| Autor: | Nathan C. Gianneschi, Matthew P. Thompson, Christopher V. Barback, David J. Hall, Ti-Hsuan Ku, Miao-Ping Chien |
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| Rok vydání: | 2013 |
| Předmět: |
Materials science
Polymers Nanoparticle Nanotechnology Conjugated system Article Supramolecular assembly Mice In vivo Cell Line Tumor Fluorescence Resonance Energy Transfer Animals Humans General Materials Science Receptor Mechanical Engineering Förster resonance energy transfer Matrix Metalloproteinase 9 Mechanics of Materials Molecular Probes Biophysics Matrix Metalloproteinase 2 Nanoparticles Peptides Molecular probe Function (biology) |
| Zdroj: | Advanced Materials. 25:3599-3604 |
| ISSN: | 0935-9648 |
| Popis: | 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. To achieve this, there is tremendous interest in the development of nanomaterials capable of acting as carriers or reservoirs of therapeutics and diagnostics in vivo.[1] Generally, nanoscale particles are favored for this task[2] as they can be large enough to function as carriers of multiple copies of a given small mole cule, can display multiple targeting functionalities, and can be small enough to be safely injected into the blood stream.[3] The general goal is that particles will either target passively via the enhanced permeability and retention (EPR) effect, actively by incorporation of targeting groups, or by a combination of both.[3b,4] Nanoparticle targeting strategies have largely relied on the use of surface conjugated ligands designed to bind overexpressed cell-membrane receptors associated with a given cell-type.[5] We envisioned an alternative targeting strategy that would lead to an active accumulation of nanoparticles by virtue of a supramolecular assembly event specific to tumor tissue, occurring in response to a specific signal (Figure 1). The most desirable approach to stimuli-induced targeting would be to utilize an endogenous signal, specific to the diseased tissue itself, capable of actively targeting materials introduced via intravenous (IV) injection. Such an approach is in contrast to efforts to develop systems capable of targeting and release via the local application of external stimuli such as light[6] or magnetic fields.[7] With respect to viable endogenous signals, one could reasonably consider materials that accumulate in response to stimuli including pH changes,[8] temperature variation,[9] or redox reactions. [10] However, we aim to develop nanoparticles capable of assembling in vivo in response to selective, endogenous, biomolecular signals.[11] For this purpose, we aim to utilize enzymes as stimuli, rather than other recognition events, because they are uniquely capable of propagating a signal via catalytic amplification in vivo as in enzyme-prodrug therapy strategies.[12] |
| Databáze: | OpenAIRE |
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