Elsevier

The Enzymes

Volume 43, 2018, Pages 31-65
The Enzymes

Chapter Three - Stimuli-Responsive Nanomachines and Caps for Drug Delivery

https://doi.org/10.1016/bs.enz.2018.07.003Get rights and content

Abstract

In this review we focus on methods that are used to trap and release on command therapeutic drugs from mesoporous silica nanoparticles (MSNs). The pores in the MSNs are large enough to accommodate a wide range of cargo molecules such as anticancer and antibiotic drugs and yet small enough to be blocked by a variety of bulky molecules that act as caps. The caps are designed to be tightly attached to the pore openings and trap the cargo molecules without leakage, but upon application of a designed stimulus detach from the nanoparticles and release the cargo. Of special emphasis in this review are nanomachines that respond to stimuli administered from external sources such as light or magnetic fields, or from chemical stimuli produced by the biological system such as a general change in pH or redox potential, or a highly specific chemical produced by a cancer cell or infectious bacterium. The goal is to release a high local concentration of the cargo only where and when it is needed, thus minimizing off-target side effects. We discuss sophisticated reversible nanomachines but also discuss some useful caps that simply break off from the nanoparticles in response to the selected stimulus. Many ingenious systems have been and are being designed; we primarily highlight those that have been demonstrated to operate in vitro and/or in vivo. In most cases the closed MSNs are endocytosed by diseased or infected cells and opened inside the cells to release the drugs. We begin with an overview of the nanoparticles and nanomachines and then present examples of drug release triggered by internal chemical stimuli from the organism and finally by external light and magnetic field stimuli.

Section snippets

Introduction and Background

Major objectives in nanomedicine and nanotherapy include: the ability to trap therapeutic molecules inside of nano-carriers; carry therapeutics to the site of the disease with no leakage; release high local concentrations of drug; release only on demand—either autonomous or external; and kill the cancer or an infectious organism. In this review we focus on mesoporous silica nanoparticles (MSNs) as the nano-carriers and nanomachines or related capping agents to trap, carry and release

Internal/Autonomous Stimuli-Responsive Drug Delivery

The bulk of the nano-carriers reported in the recent literature are ones that respond to changes in pH or redox potential in the interiors of cells such as lowering of pH on endocytosis or changes of redox potential between the extracellular environment and the cytosol after cellular uptake of the nano-carriers.

Light-Activated Nanomachines

Light-responsive drug delivery systems based on MSNs provide the advantage of remote control of the stimulated release. In addition, the high spatial resolution of photo-activation makes spatiotemporal release control feasible. Photo-activated drug delivery systems offer the potential of enhancing the treatment efficacy and reducing premature cargo release that can cause undesirable side effects. Mechanized MSNs that have photo-responsive cargo release properties are discussed in the following

Future Directions

Our review of stimuli-responsive release mechanisms emphasizes the nanomachines and caps that control the release, but they are not the only molecules that can be present. Many of the MSNs in this review carried not only the nanomachine, but also fluorescent dyes for imaging, targeting agents toward cancer cells, or all three. Future work in this area will undoubtedly use combinations of functionalities not only to enhance therapeutic applications but also for sensing leading to image guided

Acknowledgments

We thank the Defense Threat Reduction Agency Grant HDTRA1-13-1-0046 and the Zink Student Research Support fund for financial support.

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