The effect of quantum dots on synaptic transmission and plasticity in the hippocampal dentate gyrus area of anesthetized rats.

Abstract

Recently, quantum dots (QDs) have attracted widespread interest in biology and medicine. They are rapidly being used as new tools for both diagnostic and therapeutic purposes. Critical issues for further applications of QDs include the assessment of biocompatibility and biosafety of QDs. Most of previous researches concerning QD cytotoxicity focused on in vitro studies. In the present study, the impairments of acute exposure to well-modified and unmodified QDs (streptavidin-CdSe/ZnS and CdSe QDs, respectively) on synaptic transmission and plasticity were examined in adult rat hippocampal dentate gyrus (DG) area in vivo. The input/output (I/O) functions, paired-pulse ratio (PPR), field excitatory postsynaptic potential (fEPSP) and population spike (PS) amplitude were measured. The results showed that PPR and long-term potentiation (LTP) were all significantly decreased in these two types of QD-exposed rats compared to those in control rats. While the I/O functions and the amplitudes of fEPSP slope and PS amplitude of the baseline were significantly increased under QD exposure. These findings suggest that exposure to QDs, no matter whether they are well modified or not, could impair synaptic transmission and plasticity in the rat DG area in vivo and reveal the potential risks of QD applications in biology and medicine, especially in the toxin-susceptible central nervous system (CNS).

Full text

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The effect of quantum dots on synaptic transmission and plasticity in the
hippocampal dentate gyrus area of anesthetized rats
Mingliang Tanga,1, Zhifeng Lia,1, Liang Chena, Tairan Xinga, Yong Hub, Bo Yanga,
Di-Yun Ruana, Fei Suna, Ming Wanga,*
aDepartment of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, P.R. China
bDepartment of Pathology, No. 105 Hospital of the People Liberation Army, Hefei, Anhui 230011, P.R. China
a r t i c l e i n f o
Article history:
Received 17 April 2009
Accepted 8 June 2009
Available online 28 June 2009
Keywords:
Biocompatibility
Nanoparticles
Long-term potentiation
Quantum dots
a b s t r a c t
Recently, quantum dots (QDs) have attracted widespread interest in biology and medicine. They are
rapidly being used as new tools for both diagnostic and therapeutic purposes. Critical issues for further
applications of QDs include the assessment of biocompatibility and biosafety of QDs. Most of previous
researches concerning QD cytotoxicity focused on in vitro studies. In the present study, the impairments
of acute exposure to well-modified and unmodified QDs (streptavidin-CdSe/ZnS and CdSe QDs,
respectively) on synaptic transmission and plasticity were examined in adult rat hippocampal dentate
gyrus (DG) area in vivo. The input/output (I/O) functions, paired-pulse ratio (PPR), field excitatory
postsynaptic potential (fEPSP) and population spike (PS) amplitude were measured. The results showed
that PPR and long-term potentiation (LTP) were all significantly decreased in these two types of QD-
exposed rats compared to those in control rats. While the I/O functions and the amplitudes of fEPSP slope
and PS amplitude of the baseline were significantly increased under QD exposure. These findings suggest
that exposure to QDs, no matter whether they are well modified or not, could impair synaptic trans-
mission and plasticity in the rat DG area in vivo and reveal the potential risks of QD applications in
biology and medicine, especially in the toxin-susceptible central nervous system (CNS).
? 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Quantum dots (QDs) are nanometer-scale semiconductor crys-
tals which are emerging as a newclass of fluorescent probe for both
in vitro and in vivo imaging [1,2]. In comparison with current flu-
orophores, such as organic dyes and fluorescent proteins, QDs have
outstanding optical and electronic properties: broad excitation
spectrum, narrow emission spectrum, good photostability and long
fluorescent lifetime [3]. At present, perhaps one of the most
attractive and promising applications of QDs is the in vivo imaging
for further diagnostic and therapeutic purposes. So far, among
those successful in vivo use of QDs reported by several groups, the
biological targets of QDs include tumours [4–6], vasculature in
normal tissues [7], and also a number of targets after in vivo
injection of QDs [8]. With respect to these and future in vivo
applications, cautions should be exercised with QDs due to
their potential acute and long-term toxicity. In fact, QDs show
cytotoxicity to some extent under certain experimental conditions,
such as a decrease in cell viability and impairment of cell structures
and functions [9–13]. However, most of these evaluation of QD
toxicity were done in in vitro studies, which lagged behind their
in vivo applications.
Quantum dots with certain coatings, such as TAT (a cell pene-
trating peptide), were proved to be capable of crossing the blood–
brain barrier (BBB) rapidly and effectively, thus they were used to
label brain tissue [14]. This technique is followed by subsequent
worries about the potential toxicity of these foreign nanoparticles
in the toxin-susceptible brain. A number of mechanisms have been
postulated tobe responsible for QD toxicity, including desorption of
free Cd2þfrom QD core, free radical formation and interaction of
QDs with intracellular components [15]. Our previous studies
showed that unmodified CdSe QDs could elevate intracellular Ca2þ
levels and impair the functional properties of sodium channels in
the primary cultures of hippocampal neurons [13]. These may
interfere with the process of synaptic transmission and plasticity,
then impair normal functions of brain.
To determine whether QD treatment could induce impairments
of synaptic transmission and plasticity related to learning and
memory, in the present study, we investigated the input/output
* Corresponding author. Tel./fax: þ86 551 3607274.
E-mail address: wming@ustc.edu.cn (M. Wang).
1Co-first author, the two authors contribute equally to this work.
Contents lists available at ScienceDirect
Biomaterials
journal homepage: www.elsevier.com/locate/biomaterials
0142-9612/$ – see front matter ? 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.biomaterials.2009.06.012
Biomaterials 30 (2009) 4948–4955

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functions (I/O), paired-pulse ratio (PPR) and LTP of QD-exposed
groups under different doses in hippocampal DG area of the
anesthetized rats in vivo. Our results clearly delineate QD toxicity in
vivo and indicate that more research should be done to assess the
risk of the nascent nanoparticle industry.
2. Materials and methods
2.1. Quantum dot preparation
Two types of QDs were used in this study. One is the unmodified CdSe QDs with
2–3 nm in diameter, the other is the well-modified streptavidin-conjugated CdSe/
ZnS QDs with 15–20 nm in diameter and the emission maximum near 525 nm. The
former were synthesized and provided by Professor J.-G. Hou and Professor X.-P.
Wang and co-workers (Structure Research Laboratory, University of Science and
Technology of China). More details can be found in their published report [16]. The
latter were purchased from Molecular Probes Inc. (QDot 525, Eugene, OR, USA). QDs
were dialyzed just before the experiments for cadmium-free environment.
2.2. Experimental animals and quantum dot treatment
Theexperimentswerecarriedouton50adultWistarratsweighing120–200 gfeed
with tap water and purina rodent chow. At the age of 80–100 days, the animals were
utilized for extracellular recording in area DG of hippocampus of anesthetized rats in
vivo. At the day of experiment, the rats were divided into five groups which include
salinecontrol(n¼11),10 nMstrep-CdSe/ZnS QD-exposedgroup(n¼10),0.5 nMstrep-
CdSe/ZnS QD-exposed groups (n¼10), 10 nM CdSe QD-exposed group (n¼9) and
0.5 nM CdSe QD-exposed group (n¼10). After recording the baseline for 20 min, 5 mL
unmodified CdSe QDs or strep-CdSe/ZnS QDs were delivered to the hippocampal DG
area through a microsyringe pump (World Precision Instrument, Sarasota, FL, USA) at
a speed of 0.25 mL/min. Then the effects of QDs on the baseline, I/O, PPR and LTP were
recorded orderly. Not more than two animals per litter were utilized for a given
experimental measure in the same group. The care and use of animals in these
experiments followed the guidelines and protocol approved by the Care and Use of
Animals Committee of the University of Science and Technology of China. All efforts
were made to minimize the number of animals used and their suffering. All experi-
mentsconformedtotheU.S.NationalInstitutesofHealthGuidefortheCareandUseof
Laboratory Animals (NIH publication No. 80-23, revised 1996).
2.3. Histological staining
After the experiments, the brains were rapidly removed and immersion fixed in
10% formalin. For confirmation of recording position, after dehydration in graded
ethanol and xylene, the hippocampi were paraffin-embedded and cut into 4 mm
thick coronal sections. The sections were then stained using hematoxyline/eosin
(HE) according to the standard procedures and observed under an Olympus BX51
light microscope (Olympus, Tokyo, Japan). For confirmation of success of QD
delivery, sections of 20 mm thickness were cut on freezing microtome (Leica CM
1900, Bensheim, Germany) then visualized by confocal laser scanning microscope
(Carl Zeiss, Heidenheim, Germany).
2.4. Stimulation and recording
In each recording session, rats were anesthetized with urethane (1.8 g/kg, i.p.
injection) and fixed in a stereotaxic head-holder. The skull was exposed and the
animal’s body temperature, heart rate and electrocardiogram were monitored. A
concentric bipolar stimulating electrode was placed in the lateral perforant path
(coordinates with the skull surface flat: 8.0 mm posterior to bregma, 4.2 mm lateral
tothe midline, and 2.8–3.0 mm below the surface of the skull). A recording electrode
was placed in the DG (coordinates with the skull surface flat: 3.8 mm posterior to
bregma, 2.1 mm lateral to the midline, and 3.0–3.5 mm below the surface of the
skull). The recording electrode assembly consisted of a pair of Teflon-coated stain-
less steel wire electrodes, which were cut so that the distal tip of the electrode was
located 500 mm below the tip of the cannula (24 gauge, Plastics One, Roanoke, VA,
USA). When a positive-going fEPSP of maximum slope was obtained in the dentate
hilus, an inner ‘‘infusion’’ cannula (28 gauge) was inserted. The tip of the infusion
cannula protruded 400 mm below the end of the guide.
2.5. Input/output function
I/O curve was generated by systematic variation of the stimulus current by steps
of 0.1 mA (0.1–1.0 mA) in order to evaluate synaptic potency. Stimulus pulses were
delivered at 0.05 Hz and three responses at each current level were averaged.
2.6. Paired-pulse reaction
PPR was evaluated by increasing the inter-pulse intervals (IPIs,10–800 ms). The
stimulus current intensity was adjusted at intensity yielding 40–60% of the maximal
amplitude of population spike (PS). Stimulus pairs were delivered at 0.05 Hz and
three responses were averaged at each IPI.
2.7. Long-term potentiation
In present study, LTP was recorded in each animal. The stimulus intensity
selected for baseline measurements was adjusted to yield about 40–60% of its
maximal amplitude at 20 s intervals (0.05 Hz). After 20 min baseline recordings,
a high frequency stimulus (HFS) was applied (250 Hz, 1 s). Posttetanic recordings
were performed for 1 h with single pulse applied at a frequency of 0.05 Hz. At the
end of each recording session, small electrolytic lesions (10 mA, 10 s) were made to
permit histological verification of the tip position of the electrodes.
2.8. Measurement of oxidative stress
To assess the level of oxidative stress in Wistar rats after treatment with QDs,
various parameters related to oxidative stress, such as the activity of superoxide
dismutase (SOD), the level of reduced glutathione hormone (GSH) and malondial-
dehyde (MDA) were measured. SOD, GSH and MDA detection kits were used (Jian-
cheng Corp., Nanking, China), and procedures were carried out according to the
instructions of the manufacturer. Briefly, after the electrophysiological recordings,
the hippocampus was quickly removed from the experimental rat and was prepared
as 10% (w/v) homogenate in cold saline. The homogenate was centrifuged at
4000 rpm for 15 min at 4?C, supernatant was collected and stored at ?80?C for use.
The detailed procedures can be found in our previous publication [17].
2.9. Total protein determination
The concentration of total protein in the 10% (w/v) homogenates (prepared in
saline) of hippocampus was determined with the total protein quantification kit by
spectrophotometry (Jiancheng), and bovine serum albumin (BSA) was used for the
standard protein curve.
2.10. Data analysis
The fEPSP slope was measured on the rising phase of fEPSP by measuring the
slope at a fixed latency (0.5 ms) from fEPSP onset. The PS amplitude was measured
Fig.1. Position of recording electrode and confirmation of QD delivery. 4 mm thickness
brain slices were stained with hematoxyline/eosin, the recording electrode was placed
in the DG area (A). QDs were successfully delivered to the hippocampus (B). Arrows
indicate the position of electrodes. Scale bar ¼200 mm.
M. Tang et al. / Biomaterials 30 (2009) 4948–4955 4949

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by averaging the distance from the negative peak to the preceding and following
positive peak. All values were presented as mean?SEM. Comparisons between each
two given current levels or each two given IPIs or each two given time-points were
analyzed by one-way ANOVA. Comparisons between each two groups were
analyzed by two-way ANOVA with Tukey test. Probabilities less than 0.05 were
considered as significantly different.
3. Results
Fig.1A shows the accurate position of recording electrode in our
electrophysiological recordings. Fig. 1B confirms the success of QD
delivery.
3.1. Baseline
After recording the baseline for 20 min, 5 mL QDs were delivered
with a total of 20 min. Fig. 2 illustrates the effects of strep-CdSe/ZnS
QDs and unmodified CdSe QDs on the fEPSP slope and PS amplitude
of the baseline in the DG area of rat. Table 1 summarizes the extents
of fEPSP slope and PS amplitude of the baseline in different groups.
As shown in Table 1, compared to those in saline control rats
(n¼11), the normalized averaged amplitudes of fEPSP slope and PS
amplitude in the last 120 min were significantly increased in both
0.5 and 10 nM strep-CdSe/ZnS QD-treated groups (both n¼10, all
Fig. 2. Effects of streptavidin-conjugated CdSe/ZnS QDs and unmodified CdSe QDs on baseline of fEPSP slope and PS amplitude in DG area. (A, B) Acute applications of 0.5 or 10 nM
streptavidin-conjugated CdSe/ZnS QDs for 20 min significantly enhanced the amplitudes of both (A) fEPSP slope (n¼10, F¼ 24.25 and p<0.05; n¼10, F¼19.91 and p<0.05,
respectively) and (B) PS amplitude (n¼ 10, F¼ 16.59 and p<0.05; n¼10, F¼9.36 and p<0.05, respectively). (C, D) Exposure to 0.5 or 10 nM unmodified CdSe QDs for 20 min also
significantlyelevatedtheamplitudesofboth(C)fEPSPslope(n ¼10,F¼10.27andp<0.05;n¼9,F¼7.53andp<0.05,respectively)and(D)PSamplitude(n¼10,F¼17.11andp< 0.05;
n¼9, F¼16.44 and p< 0.05, respectively). All traces show mean?SEM. * shows significant difference compared with controls (n¼11). The horizons indicate the delivery of QDs.
Table 1
The averaged fEPSP slope and PS amplitude in baseline and LTP and PPR in the different groups of rats.
fEPSP slope (mean?SEM) (%)
Baseline
PS amplitude (mean?SEM) (%)
Baseline
PPR at IPI¼60 ms (mean ?SEM)
LTPLTP
Saline control (n¼11)
0.5 nM strep-CdSe/ZnS QD (n¼10)
10 nM strep-CdSe/ZnS QD (n¼10)
0.5 nM CdSe QD (n ¼10)
10 nM CdSe QD (n ¼9)
aSignificantly different from saline control.
bSignificantly different from strep-CdSe/ZnS QD groups at the same concentration.
101 ?2
112 ?2a
112 ?5a
126 ?9a
115 ?8a
135?3
106 ?1a
104 ?2a
105 ?1a
99 ?1a
99?2
135?11a
139?10a
133?12a
147?16a
188 ?5
154 ?6a
124?3a
116 ?2a,b
105 ?1a,b
204 ?29
239?29
138?9a
130?8a,b
139?18a
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p<0.05). They were also significantly increased in 0.5 and 10 nM
unmodified CdSe-treated groups (n ¼ 10 and n ¼ 9, respectively, all
p < 0.05).
3.2. Input/output functions
To test whether acute application of QDs could affect basic
synaptic transmission in rat hippocampal DG area, the I/O functions
were measured before induction of LTP. Compared with control
group (n¼11), the I/O curves of both fEPSP slope and PS amplitude
in 10 nM strep-CdSe/ZnS QD-treated group (n¼10, Fig. 3A and B)
and in 10 nM CdSe QD-treated group (n¼9, Fig. 3C and D) were
significantly enhanced, while there was no significant differences
between control and 0.5 nM strep-CdSe/ZnS QD-treated group
(n¼10, p>0.05, p>0.05). Specially, unlike strep-CdSe/ZnS QDs,
even 0.5 nM unmodified CdSe QDs could significantly elevate the
fEPSP slope when compared with control (n¼10, p<0.05). This
suggests that acute application of high dose of QDs might enhance
basic synaptic transmission in DG area of hippocampus evoked by
single-shock stimulation applied to perforant path and increased
synchronous firing of dentate granule cells.
3.3. Pair-pulse ratio
To examine whether QDs could impair short-term synaptic
plasticity in DG areaof rat hippocampus, pair-pulse ratio(PPR) of PS
amplitude was measured by the second pulse stimulus-induced PS
amplitude to the first pulse stimulus-induced PS amplitude ratio
(Figs. 4 and 6). As summarized in Table 1, the average peak facili-
tation at IPI¼60 ms in 10 nM strep-CdSe/ZnS QD-treated group
(n¼10, p<0.05), 0.5 and 10 nM unmodified CdSe QD-treated
groups (n¼10 and n¼9, respectively, both p<0.05) were all
significantly decreased when compared to that of control (n¼11),
while there was no statistic difference between that in 0.5 nM strep-
CdSe/ZnS QD-treated group (n¼10, p>0.05) and that of control.
The facilitation period duration in both 0.5 and 10 nM strep-CdSe/
ZnS QD-treated groups (142 and 48 ms, respectively) and in both
0.5 and 10 nM unmodified CdSe QD-treated group (224 and 266 ms,
respectively) was less than that in control (268 ms).
3.4. Long-term potentiation
Further, to explore if QD treatment could impair long-term
synaptic plasticity in DG area, the long-term potentiation (LTP) was
Fig. 3. Input/output (I/O) curves (mean ?SEM) of the fEPSP slope (A, C) and PS amplitude (B, D) in DG area in the control group (n ¼11), the 0.5 and 10 nM streptavidin-conjugated
CdSe/ZnS QD-treated groups (both n ¼10) and the 0.5 and 10 nM unmodified CdSe QD-treated groups (n ¼10 and n ¼9, respectively) as a function of stimulus intensity before
induction of LTP. Both (A) fEPSP slope (F¼25.67, p <0.05) and (B) PS amplitude (F¼ 32.71, p <0.05) were significantly enhanced in the 10 nM streptavidin-conjugated CdSe/ZnS QD-
treated group. Also, both (C) fEPSP slope (F ¼27.77, p< 0.05) and (D) PS amplitude (F¼19.91, p< 0.05) were significantly enhanced in the 10 nM CdSe QD-treated group. Meanwhile,
0.5 nM CdSe quantum dots significantly enhanced (C) fEPSP slope (F ¼14.79, p< 0.05). * shows significant difference compared with control.
M. Tang et al. / Biomaterials 30 (2009) 4948–49554951

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induced by a high frequency stimulus (HFS) (250 Hz,1 s). Effects of
QDs on the LTP of fEPSP slope and PS amplitude are shown in Figs. 5
and 6. When estimated from fEPSP slope and PS amplitude, the LTP
amplitudes in both 0.5 and 10 nM strep-CdSe/ZnS QD-treated
groups (both n¼10, all p<0.05, Table 1) were all significantly
decreased compared with those of control (n¼11), and they were
also significantly depressed in 0.5 and 10 nM CdSe QD-treated
groups (n¼10 and n¼9, respectively, all p<0.05, Table 1).
Although these two kinds of QDs could both depress the LTP, the
CdSe QDs treatment decrease the LTP of PS amplitude to a greater
extent when compared to the same concentration of strep-CdSe/
ZnS QDs treatment (both p<0.05, Table 1).
3.5. Oxidative stress measures
Fig. 7 summarizes the selected parameters, which indicate the
extent of oxidative stress in hippocampus. Both unmodified CdSe
QDs and strep-CdSe/ZnS QDs could significantly increase MDA
concentration, SOD activity and GSH level compared with those of
control. The MDA concentrations in 0.5 nM unmodified CdSe QD-
treated group, 10 nM unmodified CdSe QD-treated group, 0.5 nM
strep-CdSe/ZnS QD-treated group and 10 nM strep-CdSe/ZnS QD-
treated group were significantly increased to 1.57?0.09 nmol/
mgprot(n¼10,
p<0.05), 1.81?0.08 nmol/mgprot
1.77?0.09 nmol/mgprot (n¼9, p<0.05), respectively, compared
with that of control (1.32?0.11 nmol/mgprot, n¼11). The SOD
activity in these groups was also significantly increased compared
to that of control (control: 135.1?5.2 U/mgprot, n¼11; 0.5 nM
CdSe QD-treated group: 154.2 ?6.3 U/mgprot, n¼10, p<0.05;
10 nM
CdSeQD-treatedgroup:
p<0.05; 0.5 nM strep-CdSe/ZnS QD-treated group: 173.2?5.5 U/
mgprot, n¼10, p<0.05; 10 nM strep-CdSe/ZnS QD-treated group:
174.8?6.1 U/mgprot, n¼9, p<0.05). The GSH levels in these four
QD-treated groups were also significantly increased compared with
that of control (control: 32.33?4.12 mg/gprot, n¼11; 0.5 nM CdSe
QD-treated group: 44.11?5.08 mg/gprot, n¼10, p<0.05; 10 nM
CdSe QD-treated group: 47.29?4.07 mg/gprot, n¼10, p<0.05;
0.5 nM strep-CdSe/ZnS QD-treated group: 60.69?7.21 mg/gprot,
n¼10,
65.23?5.29 mg/gprot, n¼9, p<0.05).
p<0.05), 1.62?0.12 nmol/mgprot
(n¼10,
(n¼10,
andp<0.05)
157.7?4.9 U/mgprot,n¼10,
p<0.05; 10 nM
strep-CdSe/ZnSQD-treatedgroup:
4. Discussion
So far, one of the most exciting biomedical applications of QDs
may be the in vivo animal targeting and imaging due to their
excellent long-term photostability. At present, there were some
positive reports about the use of QDs for in vivo applications, such
as diagnosis as well as treatment of cancers using QDs [4,6,18] and
imaging normal tissues [6,8,19–21]. Especially, TAT-conjugated
QDs, intra-arterially delivered to the rat brain, were successfully
usedtolabel the brain tissuewithout manipulating theblood–brain
barrier (BBB) [14]. Lately, TAT-conjugated nanoparticles could be
employed for the central nervous system (CNS) delivery of anti-HIV
drugs [22]. These applications demonstrate that nanoparticles,
such as QDs, can effectively overcome BBB and accumulate in the
brain, further may endanger the normal function of the brain. In
fact, in vivo imaging with QDs encounters many obstacles, one of
the biggest of which is the potential for QD toxicity in animal and
human applications. Detailed examination of the biocompatibility
and biosafety of QDs should be done for further human clinical use.
Many invitro studies confirmed that QDs could impaircell structure
andfunction, even induce cell death [9–11,13]. Althoughthereis not
enough evidence yet that QDs can present detectable toxicity in
living animals, an in vivo study suggests that astrocytes in the
brains of transgenic mice could be activated following adminis-
tration of several different QDs including CdTe and CdSe QDs [23],
and this is the first direct evidence showing that there is potential
for QD interfering with the normal brain functions.
Hippocampus has been identified as a critical area for certain
formsoflearningandmemory,herewechosehippocampustobethe
spot to examine QD acute toxicity on synaptic transmission and
plasticity. I/O functions can represent the basal response, reflecting
notonlythelevelofpresynapticneurotransmitterreleasebutalsothe
postsynapticreceptorresponse.Acuteexposureto10 nMeitherstrep-
CdSe/ZnS QDs or unmodified CdSe QDs could significantly increase
the I/O functions (Fig. 3), indicating that QDs enhanced the basal
synaptic transmission and plasticity in DG area. Similarly, acute
applications of 0.5 and 10 nM either strep-CdSe/ZnS QDs or unmod-
ified CdSe QDs for 20 min increased the baseline of both fEPSP slope
and PS amplitude (Fig. 2), suggesting that QDs enhanced synaptic
efficiency in this area. Our previous studies showed that acute
application of QDs was capable of elevating intracellular Ca2þ
Fig. 4. Paired-pulse ratio (PPR) of the PS amplitude in DG area at varying inter-pulse
intervals (IPI) of 10–800 ms in the control group (n ¼11), the 0.5 and 10 nM strepta-
vidin-conjugated CdSe/ZnS QD-treated groups (A) (both n ¼10), and 0.5 and 10 nM
unmodified CdSe QD-treated groups (B) (n ¼10 and n ¼9, respectively). Exposure to
10 nM streptavidin-conjugated CdSe/ZnS QDs (F¼16.26, p <0.05) or 0.5 and 10 nM
CdSe QDs (F ¼21.22, p<0.05 and F¼18.14, p<0.05, respectively) significantly
decreased the peak facilitation at IPI¼ 60 ms. The arrows indicate the peak facilitation
and facilitation period duration. All traces show mean ?SEM.
M. Tang et al. / Biomaterials 30 (2009) 4948–49554952