Biomedical Engineering Reference
In-Depth Information
Fig. 9
HepG2 cells (labeled with EB to show
red color
) incubated for 6 h with (
a
) FITC-
SiO
2
-NH
2
and (
b
) FITC-SiO
2
-Tat3.5 particles. Bar is 10 mm. (Reprinted from Mao et al.
2010
,
Copyright (2010), with permission from Elsevier)
4.3
Controlled and Targeted Delivery
4.3.1
Tuning Silica-Based System to Control the Intracellular Delivery
To answer the problem of drugs side effects, controlled drug delivery devices are
being developed. These systems will prevent drug leakage or premature release,
thus diminishing the necessary dose administered. Such systems can be obtained by
grafting stimuli-responsive tethers on silica-based nanoparticles. These tethers will
act as gatekeepers that could be triggered either by an intracellular signal (such as
pH, reducing environment, competitive binding, enzymatic activity) or an external
signal (such as light, ultrasound, electromagnetic field, temperature). For instance,
silica nanoparticles with pH-sensitive gates have been developed (Cauda et al.
2010
). This device is based on the sealing of the mesopores in acidic conditions via
an interaction between two different grafted groups: sulfonate and amine. When pH
reaches a physiological value, the previous interaction ceases to exist leading to the
gradual opening of the pores and the release of the encapsulated drug. But practical
problems can be encountered while designing such devices and for instance the
pore size has to be adjusted in order to obtain an effective gate because if the pore
is too large, the release takes place with no incidence of the pH. This implies that
the gating system must be matched with the pore size opening. Another example
would be to use cyclodextrin as a glutathione sensitive gatekeeper (Kim et al.
2010
). The principle is the same: cyclodextrin groups are covalently grafted on the
external surface of mesoporous silica nanoparticles via a disulfide bond and mask
the opening of the pores. When the particles are in a glutathione containing envi-
ronment (e.g. in the targeted cell) the disulfide bond is cut, releasing the cyclodextrin
Search WWH ::
Custom Search