Biomedical Engineering Reference
In-Depth Information
observed for the former. This was attributed to much more effective endosomal escape
based on the PEG detachment in endosome. The same research group has recently
developed the polyplex micelle with a disulfide cross-linked core, which is character-
ized by the efficient release of the loaded siRNA responding to intracellular reductive
conditions. As a result, this type of vector achieved 100-fold higher siRNA transfec-
tion efficacy compared with non-cross-linked polyplexes from PEG-
b
-PLL, which
were less stable at physiological ionic strength (Matsumoto et al.
2009
).
3.9.3
Temperature-Responsive Vectors
Temperature is one of the safest and most controllable external stimuli. Hyperthermia
therapy via microwave has long been adopted for tumor therapy (Needham and
Dewhirst
2001
). PNIPAm is the most studied synthetic responsive polymer, which
undergoes a sharp coil-globule transition in water at about 32°C, changing from a
hydrophilic state to a hydrophobic state (Schild
1992
). So far, most of the temper-
ature-responsive vectors are based on PNIPAm-containing materials (Yokoyama
2002
). For example Hinrichs et al. have synthesized thermosensitive copolymers
of NIPAm (temperature-sensitive monomer) and DMAEMA (positively charged
unit) and investigated the transfection efficiency in ovarian cancer cells (Hinrichs
et al.
1999
). The temperature sensitivity was found to be dependent on the poly-
mer/pDNA ratio. However, no direct correlation between transfection efficiency
and polymer LCST was found. By copolymerizing NIPAm and DMAEMA with
hydrophobic butylmethacrylate, Kurisawa et al. developed a terpolymeric gene
carrier that displayed temperature-controlled gene expression in COS1 cells
in vitro
(Kurisawa et al.
2000
; Yokoyama et al.
2001
). Other PNIPAm-bearing
polycations such as PEI have also been synthesized to study the effect of tempera-
ture on the physicochemical characteristics of polyplexes and transfection activity
(Twaites et al.
2004
).
3.9.4
Photoresponsive Delivery Vectors
Photo-irradiation has been used to enhance the transfection efficiency by improving
both the endosomal escape of exogenous DNA and the DNA release from com-
plexes, since light is an easily controllable stimulus.
Høgest and colleagues have proposed photo-chemical internalization (PCI) for
drug and gene delivery (Høgset et al.
2004
). PCI is based on photochemical reac-
tions initiated by a photosensitizer localized in endocytic vesicles such as endo-
somes and lysosomes, inducing the rupture of these vesicles upon light illumination.
Photosensitizers, such as porphyrins and phthalocyanines, are compounds that
make cells extraordinary sensitive to light irradiation. Photochemical transfection
using a photosensitizer, aluminum phthalocyanine, PLL/DNA polyplexes showed a
20-fold higher transfection efficiency of GFP in human melanoma cell line upon
light treatment, reaching transfection levels of about 50% of the surviving cells
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