Biomedical Engineering Reference
In-Depth Information
motif was described by Chen et al. (2011). These micelles rupture and release their therapeutic
payload in response to irradiation with UV light (365 nm). This disruption in the micelle's structure
is caused by the DNQ motif, which upon irradiation switches from hydrophobic DNQ to hydro-
philic 3-indenecarboxylic acid. In order to evaluate the biocompatibility of this new material, the
authors utilized the MTT assay. Following a 24 h incubation of the CPEG-
g
-DNQ micelles with
both HepG2 and HUVEC cell lines, cellular viabilities remained above 90% throughout the entire
concentration range tested (10-200 mg/L). The observed biocompatibility through the cell-based
test was attributed to the incorporation of CPEG within the polymer's structure. A major concern in
the study is that only one time point was used, coupled with the limitation that the by-products of
micelle disruption and the effects of irradiating cells with 365 nm light were not reported.
Another method utilizing a photoresponsive system was developed by Boca et al. and utilizes
chitosan-coated silver nanotriangles (Chit-AgNTs) as photothermal transducers in order to induce
local hyperthermia in tumor tissues following irradiation (photothermal ablation therapy) (Boca
et al., 2011). This system utilized NIR light (800 nm) in order to induce local hyperthermia, and
has the additional benefit of utilizing chitosan, a generally regarded as safe (GRAS) excipient
(Keefe, 2011). In this work, biocompatibility claims were based on assessment of the Chit-AgNTs
in both human cancerous cells (NCI-H460) and benign human cell (human embryonic kidney) on
the basis of changes in cellular morphology as well as counting viable cells following propidium
iodide/Hoechst double staining. Both these methods of assessment were conducted following 24 h
incubation of the Chit-AgNTs with the cells. Analysis of the cellular morphology showed that the
Chit-AgNTs treated cells showed little deviation from untreated cells, with only 3.5% of the cells
displaying an abnormal, rounded morphology. Further analysis using the double staining procedure
showed that over the concentration range tested (0.17-1.71 μg/mL), the Chit-AgNTs reduced the
viability of normal human embryonic kidney cells by less than 5%. Interestingly, the Chit-AgNTs
were significantly more cytotoxic to cancerous cells; showing cellular viabilities of 85% and 75% at
the 1.37 and 1.71 μg/mL concentrations, respectively.
Despite the intensive efforts in the development of new photoresponsive materials, investigation
into the biological effects of the light required to activate such systems has been limited. To date,
most photoresponsive materials rely on UV light to activate the system due to the exquisite sensitiv-
ity of UV-responsive chromophores. However, this poses a serious problem to the clinical relevance
of such systems due to UV light's genotoxicity and lack of tissue penetration (McMillan et al.,
2008). In order to circumvent the well-established limitations associated with UV light, as well as
to take advantage of some of the unique and beneficial characteristics of NIR light (e.g., tissue trans-
parency and biologically benign) (Zhao et al., 2007), many research groups have shifted their focus
toward the discovery/development of chromophores that respond efficiently to NIR light. Another
reason for the recent emergence of NIR light as a trigger comes as a result of recent advances in
laser technology; specifically the development of high-energy femtosecond pulsed lasers. These
new lasers are capable of activating NIR-responsive chromophores; a large step toward the clini-
cal application of NIR chromophores since to date no known NIR chromophore exists that can be
activated via a continuous wave laser (Zhao, 2007).
While the general trend in the literature is to focus on the photochemistry of these new materi-
als, some researchers have investigated the effects of NIR light on biological systems. One group
has reported that the safe dose of NIR light from a femtosecond pulsed laser is 2.5-4 nJ/laser pulse
(Wantanabe et al., 2004). This work has been often cited in many reports on new NIR-responsive
materials in lieu of conducting biocompatibility assessment of new nanomaterials and NIR light
(dose, wavelength, pulse duration, and frequency) required to activate the specific novel material
being studied. Nevertheless, Chen et al. (2006) described a photoresponsive DNA-gold nanorod
conjugate that responds to NIR light. In the work, Chen et al. used the trypan blue exclusion assay
in order to assess cellular viability of HeLa cells following varying doses of 800 nm NIR light.
Their findings indicated that 800 nm light, dosed at or below 79 μJ/pulse, did not significantly
affect cellular viability (each pulse lasted 130 femtoseconds and the pulses were delivered at 1 Hz
