Porous silica nanoparticles release trapped guest molecules in response to multiple stimuli for applications including disease diagnostics, imaging and drug delivery.
Diseases often result in the production of excess amounts of certain naturally occurring chemicals, and the detection of these ‘biomarkers’, in combination with symptoms, is often used in diagnosis. Often, higher than usual levels of biomarkers may occur before symptoms are noticed, which could aid early detection — a critical factor contributing to survival in some cases. Systems that can produce signals or even release drugs in response to the presence of such biomarkers are therefore of great interest.
Now, Chulhee Kim, Chiyoung Park and co-workers from Inha University in Incheon, Korea1 have developed porous silica nanoparticles designed to release guest molecules in response to increased levels of enzymes associated with acute pancreatitis. The silica nanoparticles are approximately 60 nm in diameter and have multiple pores with an average pore diameter of around 2.5 nm. To work as a delivery vehicle, fluorescent probes or drug molecules need to be trapped inside the pores and the open ends of the pores must be blocked. The blocking groups, or ‘gatekeepers’, then need to be removed or degraded in the presence of the chosen biomarker.
Kim and his co-workers chose β-cyclodextrin, a donut-shaped molecule, as a suitable gatekeeper. This gatekeeper molecule is degraded by α-amylase — increased levels of which are associated with acute pancreatitis. The researchers attached multiple cyclodextrins to the surface of the porous silica nanoparticles using a linker designed to be cleaved by lipase — a second enzyme known to be overproduced in cases of acute pancreatitis. This arrangement means that guest molecules can be released by two mechanisms associated with acute pancreatitis (Fig. 1).
The potential for multiple release of the molecular guests was demonstrated using a different linker to attach the β-cyclodextrin gatekeeper. This new linker incorporated a bond known to be broken upon irradiation with ultraviolet light (rather than by lipase). As hoped, the combined effect of light and the enzyme α-amylase caused the release of more guests than either mechanism alone.
References
Park, C., Kim, H., Kim, S. & Kim, C. Enzyme responsive nanocontainers with cyclodextrin gatekeepers and synergistic effects in the release of guests. J. Am. Chem. Soc. 131, 16614 (2009).
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Nanocontainers: Responsive release. NPG Asia Mater 2, 48 (2010). https://doi.org/10.1038/asiamat.2010.25
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DOI: https://doi.org/10.1038/asiamat.2010.25