Laboratory Experiment

pubs.acs.org/jchemeduc

Introducing Students to Surface Modification and Phase Transfer of

Nanoparticles with a Laboratory Experiment
Alaaldin M. Alkilany,*,† Sara Mansour,† Hamza M. Amro,† Beatriz Pelaz,‡ Mahmoud G. Soliman,‡
Joshua G. Hinman,§ Jordan M. Dennison,§ Wolfgang J. Parak,‡ and Catherine J. Murphy§
†
Department of Pharmaceutics & Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman 11942, Jordan
‡
Fachbereich Physik, Philipps Universität Marburg, 35037 Marburg, Germany
§
Department of Chemistry, University of Illinois at UrbanaChampaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United
States
*
S Supporting Information
Downloaded by UNIV DE GUADALAJARA at 10:38:08:156 on June 22, 2019
from https://pubs.acs.org/doi/10.1021/acs.jchemed.6b01003.

ABSTRACT: A simple, reliable, and cost-effective experiment is presented in which students synthesized citrate-capped gold
nanoparticles (GNPs), functionalized them with poly(ethylene glycol) (PEG), and transferred the PEG-GNPs from water to the
organic phase dichloromethane. The experiment introduces students to nanotechnology with foci on important concepts
including surface modification of nanoparticles, colloidal stability, and phase transfer. The proposed experiment was evaluated at
three different universities to confirm its reproducibility and versatility. Collectively, the proposed experiment is suitable to be
implemented into colloid- or nanoscience-related curricula.
KEYWORDS: Upper-Division Undergraduate, Laboratory Instruction, Hands-On Learning/Manipulatives, Demonstrations,
Nanotechnology, Colloids

■ INTRODUCTION
There is a growing interest in the field of nanotechnology
across both academia and industry because of the unique
physical, chemical, optical, electrical, and magnetic properties
that inorganic solids exhibit at the nanoscale; these properties
bear tremendous promise for future applications.1 As a result,
there is a need to develop educational materials to be
implemented in modern chemical curricula for students to
gain proper theoretical and practical knowledge related to
nanoscience.2 For example, in the past decade (2005−2016),
this Journal has published more than 170 papers on various
topics highlighting nanoparticle synthesis (gold,3 silver,4 iron
oxides,5 and quantum dots6), shape-controlled synthesis,7 size-
dependent optical properties,8 sensing applications of nano-
particles,9 and nanotoxicology.10 In alignment with theses
topics, appropriate surface chemistry is required to provide
colloidal stability and, in many cases, to add specific
functionalities.11 Surprisingly, detailed educational demonstra-
tions of the surface modification and/or phase transfer of
nanoparticles from aqueous to organic solution are lacking.
Herein we report a simple, reliable, and cost-effective
experiment in which undergraduate students learn to synthesize
gold nanoparticles (GNPs) using the simple Frens method,
functionalize the nanoparticle surfaces with a polymer (poly-
(ethylene glycol) methyl ether thiol, PEG-SH), and transfer the
© 2017 American Chemical Society and
Division of Chemical Education, Inc.
PEGylated gold nanoparticles (PEG-GNPs) from the aqueous
phase to an organic phase (dichloromethane, DCM). This
experiment supports specific learning outcomes related to the
field of nanoscience, highlighting the ability of student to
(1) prepare nanoparticles following standard procedures;
(2) explain the optical properties of GNPs and their
dependence on aggregation;
(3) explain the two major routes of colloidal stability of
GNPs (electrostatic and steric stabilization);
(4) perform simple surface functionalization chemistry on
the surface of GNPs, and observe how this chemistry
facilitates the transfer from water to an immiscible
organic solvent (phase transfer of nanoparticles);
(5) calculate the efficiency of the observed phase transfer.
The validity and applicability of this demonstration was
evaluated independently at three institutions: University of
Jordan (Jordan), Philipps Universität Marburg (Germany), and
University of Illinois at UrbanaChampaign (USA). Student
feedback and instructor evaluations confirmed that this
experiment can be conducted in a typical laboratory session,
Received: December 21, 2016
Revised: April 18, 2017
Published: May 9, 2017
769 DOI: 10.1021/acs.jchemed.6b01003
J. Chem. Educ. 2017, 94, 769−774
Journal of Chemical Education
and suggest the suitability of this experimental material to be
incorporated into colloid- or nanoscience-related chemistry
curricula.
■ EXPERIMENTAL PROCEDURE
The procedure for this laboratory experiment involves several
main steps, each of which is briefly summarized below.
Synthesis of Citrate-Capped Gold Nanoparticles (Cit-GNPs)
Citrate-capped gold nanoparticles (Cit-GNPs) were synthe-
sized using the well-documented Frens method12 with minor
modifications. Briefly, an aqueous solution of gold chloride salt
(HAuCl4, 50 mL, 2.5 × 10−4 M) was brought to boiling with
stirring, followed by addition of sodium citrate solution (1.25
mL, 5% w/w) to reduce the gold salt to the elemental metal
and to form Cit-GNPs. Full experimental details are included in
the instructor lab manual in the Supporting Information (SI).
PEGylation of Cit-GNPs (PEG-GNPs)
The surface modification of as-prepared Cit-GNPs with a
thiolated poly(ethylene glycol) polymer (PEG-SH, Mn = 5000
Da) was carried out using simple published protocols.13 Briefly,
an aqueous solution of PEG-SH (0.2 mL, 50 mg/mL) was
added to 10 mL of a Cit-GNPs aqueous solution in a 15 mL
centrifuge tube and mixed gently. The mixture was left to stand
for 20 min to allow for the replacement of citrate anions by
PEG-SH chains on the surface of the GNPs. Full experimental
details are included in the instructor lab manual.
Salt-Induced Nanoparticle Aggregation (Cit-GNPs versus
PEG-GNPs)
The colloidal stability of gold nanoparticles was evaluated by
observing the aggregation upon the addition of NaCl solution
(1.0 mL, 5% w/w) to 1.0 mL of either Cit-GNPs or PEG-GNPs
in a plastic cuvette. Color changes from red (well-dispersed) to
blue (aggregated) were used to evaluate nanoparticle
aggregation.
Phase Transfer of PEG-GNPs from Water to
Dichloromethane
Phase transfer of PEG-GNPs from water to an organic layer
(DCM) was carried out using a published protocol with minor
modifications.14 Briefly, 2.0 mL of DCM was placed in a glass
vial, followed by the addition of 2.0 mL of the as-prepared
PEG-GNPs solution. Phase transfer then was facilitated by the
addition of 3.0 mL of methanol. Full experimental details are
included in the instructor lab manual.
■ HAZARDS
Gloves, goggles, and laboratory coats should be worn. During
the nanoparticle synthesis step, the flask with boiling water
should be handled carefully with lab tongs. Steps involving the
use of dichloromethane should be performed in a fume hood
away from potential ignition sources.
■ RESULTS AND DISCUSSION
The lab starts with a theoretical introduction (∼1 h) to
familiarize students with the following topics:
(1) brief introduction to the field of nanotechnology;
(2) gold nanoparticle synthesis using the Frens method with
a simplified mechanistic discussion to highlight the redox
chemistry that is involved in the synthesis of Cit-GNPs
and the role of citrate ions in the synthesis;
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Laboratory Experiment
(3) the ligand exchange concept and the formation of a self-
assembled monolayer of thiolated molecules on GNPs,
with discussion of the differences between well-ordered
small-molecule thiols and large polymers containing thiol
end groups;
(4) colloidal stability (electrostatic repulsion and steric
hindrance as routs of stabilization);15
(5) aggregation of GNPs and resulting optical response,
including an introduction to surface plasmons;
(6) the dual solubility of PEG in water and DCM and the
dual stability of PEG-GNPs in both solvents;
(7) the role of methanol in the phase transfer of PEG-GNPs
from water to the organic solvent.
Students found this theoretical introduction to be extremely
helpful in understanding important concepts related to the
experimental part, as evidenced by their responses to assigned
homework that contained a series of questions (a sample is
included in the SI). More details regarding this introduction
can be found in the instructor lab manual.
Immediately after the theoretical introduction, students were
distributed into groups (2−3 students/group). To ensure that
the experiments could be performed by students in the allotted
time, stock solutions were prepared prior to the lab by the
instructor. Moreover, the lab instructor cleaned glass flasks
(100 mL) with aqua regia prior to the lab to avoid exposure of
students to these strong acids. The availability of all chemicals,
glassware, and supplies (as detailed in the instructor lab
manual) was checked prior to the lab. Brief instructions on the
proper use of micropipettes, hot-plate stirrers, and the UV−vis
spectrophotometer were delivered prior to the experimental
part. Each group worked together in all stages. However, each
student was asked to prepare his/her own lab report. The
experimental part (as detailed below) lasted for another 2
hours, resulting in a total of ca. 3 hours for both theoretical and
experimental parts.
Synthesis of Cit-GNPs
The Frens method is employed in this experiment to prepare
Cit-GNPs because of its simplicity and reproducibility. Figure 1
Figure 1. Cartoon demonstrating the synthesis of Cit-GNPs using the
Frens protocol.
shows the synthesis of Cit-GNPs by boiling an aqueous
solution of gold chloride (HAuCl4) followed by addition of
sodium citrate solution. A typical Cit-GNPs synthesis takes
around 30 min. The resulting nanoparticle solution showed a
typical ruby red color indicating the formation of GNPs (see
the video in the SI). The students were asked to take a picture
of the GNP solution (using their cell phone cameras) and to
record its UV−vis extinction spectrum using a laboratory
spectrophotometer.
DOI: 10.1021/acs.jchemed.6b01003
J. Chem. Educ. 2017, 94, 769−774
Journal of Chemical Education
PEGylation of GNPs
PEGylation (assembly of the PEG polymer on the surface of
GNPs) is a well-documented, simple, and relatively fast surface
modification of GNPs.13 The aim of this procedure is to
introduce students to different types of colloidal stabilization
routes in solution (electrostatic repulsion for Cit-GNPs vs
steric hindrance for PEG-GNPs)15 and their sensitivity to
added salt. Moreover, PEGylation is necessary to facilitate the
phase transfer from water to DCM because of the hydro-
philicity/hydrophobicity of this unique polymer.
PEGylation was carried out by addition of PEG-SH aqueous
solution to Cit-GNPs with stirring for 20 min to replace citrate
ions on the GNPs with PEG (see Figure 2 and the video in the
Figure 2. Cartoon demonstrating the surface functionalization of Cit-
GNPs with PEG-SH polymer to prepare PEG-GNPs. The displace-
ment of citrate ions on the surface of the GNPs by the thiolated
polymer molecules (PEG-SH) should be noted.
SI). Students were instructed to test the colloidal stability of
GNPs before and after PEGylation by addition of NaCl
solution, as detailed in Experimental Procedure.
Nanoparticle Aggregation Test (Cit-GNPs versus
PEG-GNPs)
It is well-known that PEGylation of nanoparticles enhances
their colloidal stability via steric hindrance.16 Students were
instructed to compare the colloidal stabilities of Cit-GNPs and
PEG-GNPs upon the addition of salt solution, as detailed in
Experimental Procedure and the SI. A clear, spontaneous, and
reproducible aggregation of Cit-GNPs was observed upon salt
addition, as evidenced by the change of solution color from red
to blue (Figure 3A). In contrast, PEG-GNPs showed excellent
colloidal stability without aggregation, as evidenced by the
constant red color before and after salt addition (Figure 3B).
An explanation regarding the observed different colloidal
stabilities of Cit-GNPs (electrostatic repulsion stabilization)
and PEG-GNPs (steric repulsion by the hydrophilic shell) was
Figure 3. Representative example of the student results on the
aggregation test. (A) Addition of NaCl to Cit-GNPs resulted in
aggregation, as evidenced by the color change from red to blue. (B)
PEG-GNPs showed a stable colloid upon addition of salt.
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Laboratory Experiment
detailed to the students in the theoretical introduction session
and can be found in the instructor lab manual.
Phase Transfer of PEG-GNPs from Water to
Dichloromethane
There are various published protocols to transfer GNPs from
water to organic phases.17 We recently developed a protocol to
transfer GNPs from water to dichloromethane using methanol
as a common solvent and thiolated PEG as a phase-transfer
agent.14 We observed that this protocol is simple, fast, and
highly reproducible, which motivated us to employ it as an
educational material in nanochemistry. Figure 4 summarizes the
phase-transfer process, which is explained in the instructor lab
manual.
Mixing DCM with PEG-GNPs in water resulted in a two-
layer system with the red phase containing PEG-GNPs on the
top, as shown in Figure 4 (DCM is denser than water).
Students were instructed to shake the vials gently and to notice
that the two phases are immiscible and no phase transfer
occurs. Efficient and spontaneous phase transfer was initiated
by the addition of methanol (a common solvent that is miscible
with both water and DCM), as shown in Figure 4 and in the
video in the SI. The roles of methanol and the PEG coating in
the phase-transfer process were discussed in detail in the
theoretical introduction session and can be found in the
instructor lab manual.
To calculate the phase-transfer efficiency, students obtained
the UV−vis extinction spectra of (1) PEG-GNPs aqueous
solution before phase transfer and (2) the aqueous upper layer
after phase transfer. The phase-transfer efficiency was calculated
using the equation
⎛ A ⎞
efficiency = ⎜1 − after ⎟ × 100%
⎝ Abefore ⎠
where Abefore and Aafter are the absorbance values at the
wavelength of the plasmon peak λmax obtained from the UV−vis
extinction spectra of the PEG-GNPs solution before phase
transfer and the aqueous upper layer after phase transfer,
respectively.
To confirm that the lower layer after phase transfer (the red
layer in Figure 5a) is the organic phase (DCM-rich phase) with
PEG-GNPs, students were instructed to pour the lower layer
after phase transfer into a beaker filled with tap water. The
formation of red droplets at the bottom of the beaker
supported the phase transfer of PEG-GNPs from water to
DCM, as shown in Figure 5b.
■ FORMATIVE ASSESSMENT
Methodology
After the experiment was conducted, formative assessment was
conducted using a homework assignment, written student
feedback, and short interviews with participating students. For
example, all of the students handed in lab reports (templates
were provided and can be found in the SI) in which they
summarized their results. Moreover, every student was
instructed to hand in a homework assignment including his/
her answers to five thematic questions that cover the most
important concepts taught in this lab (a copy can be found in
the SI). A feedback sheet that includes eight questions (a copy
can be found in the SI) was completed by each student to
assess the validity of this lab, the achievement of the learning
DOI: 10.1021/acs.jchemed.6b01003
J. Chem. Educ. 2017, 94, 769−774
Journal of Chemical Education
Figure 4. Phase transfer of PEG-GNPs from water to dichloromethane upon the addition of methanol. Note: The red line at the top of the vial to
the right is a common optical reflection of the red layer in the bottom and does not represent a true layer.
Figure 5. Beaker test. The lower red layer in the glass vial after the
phase transfer (a) is added to a beaker filled with water. The formation
of red droplets at the bottom of the beaker confirms the transfer of
PEG-GNPs to the organic layer (DCM layer).
outcomes, and how it compares to typical and related
laboratories in their curriculum.
Achieved Student Learning Outcomes
The presented laboratory is designed to provide students with
the following intended learning outcomes (ILOs), which ensure
their ability to
(1) prepare Cit-GNPs and identify the role of the reactants
used (e.g., sodium citrate as a reducing agent and a
capping agent simultaneously);
(2) explain why GNPs are red (understanding optical
properties of metals at the nanoscale);
Figure 6. UV−vis spectra of PEG-GNP solution in dichloromethane (red dashed lines) and of the aqueous upper layer (blue solid lines) (A) without
and (B) with dilution with methanol (1:1 v/v).
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Laboratory Experiment
(3) relate the colloidal stability of Cit-GNPs to the
electrostatic repulsion mechanism and explain the
aggregation upon salt addition;
(4) functionalize the surface of Cit-GNPs with PEG polymer,
evaluate the different colloidal stabilities of Cit-GNPs
and PEG-GNPs upon salt addition, and provide an
explanation for this observation;
(5) carry out an efficient phase transfer of PEG-GNPs from
water to DCM and discuss the roles of the PEG shell and
methanol in this process;
(6) obtain UV−vis spectra of the GNP solutions and
calculate the phase-transfer efficiency.
Achievement of ILOs of the proposed laboratory was evaluated
using multiple formative assessment methods, including (1) in-
lab evaluation looking for the ability of student to perform the
reaction properly, (2) lab reports, and (3) questions in the form
of a homework assignment. For each ILO, methods of learning,
methods of assessment, results of the assessment, and a final
conclusion regarding the achievement of the ILO are listed in
Table S3 in the SI. Collectively, our results suggested
satisfactory achievement of the ILOs.
Observed Deviation/Difficulties
Generally, all lab stages (theoretical orientation, synthesis of
Cit-GNPs, surface modification with PEG, and phase transfer)
were carried out by students with satisfactory reproducibility
and rate of success at the three institutions. However, for one
student group, the prepared Cit-GNPs solution appeared
lighter than the typical color. After investigation, it was found
that the students did not pipet the proper amount of gold
solution. With this in mind, we suggest that lab instructors
demonstrate the proper use of pipettes to students prior to the
laboratory.
Another observed difficulty was related to calculating the
transfer efficiency of PEG-GNPs from water to DCM. The
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Journal of Chemical Education
protocol instructs the students to compare the absorbance
values at λmax for PEG-GNPs solution before phase transfer
(Abefore) and the aqueous upper layer after transfer (Aafter). The
more efficient the phase transfer is, the more color will
disappear from the aqueous upper layer as a result of the
transfer of PEG-GNPs from water to DCM. In all of the
student experiments, the phase transfer of PEG-GNPs from the
aqueous layer to the DCM layer was very efficient, as evidenced
by the complete disappearance of the red color of the upper
layer. However, the upper layers in some cases were colorless
and turbid instead of colorless and clear as a result of the
formation of an unstable water/DCM emulsion. This turbidity
resulted in light scattering during the collection of the UV−vis
extinction spectra, thus resulting in spectra with elevated
baselines (Figure 6A). This elevated baseline resulted in a false
high Aafter and ultimately a false low phase-transfer efficiency.
To prevent the formation of a stable emulsion and thus to
eliminate the observed turbidity, a 1:1 dilution with methanol
for both solutions (PEG-GNPs solutions before phase transfer
and the aqueous upper layer after phase transfer) was necessary.
This simple remedy was found to be extremely beneficial to
eliminate turbidity and thus an erroneous determination of the
phase-transfer efficiency (Figure 6B). In principle, the
instructor could use this kind of data to start a discussion
about the limits of UV−vis spectroscopy and how scattering
can produce what appears to be “absorbance”. All of the
students calculated high phase-transfer efficiency values
(>90%). UV−vis extinction spectra and calculation examples
are available in the student report samples in the SI.
■
CONCLUSION
This combined laboratory/lecture exercise introduced students
to a simple method to prepare GNPs and to functionalize their
surfaces with thiolated polymers. The comparison between the
colloidal stabilities of Cit-GNPs and PEG-GNPs upon the
addition of salt allowed students to visually understand
important concepts related to colloidal stability and the effect
of different surface chemistries and stabilization mechanisms.
Moreover, students were introduced to a simple and
reproducible method to transfer GNPs from an aqueous
phase to an organic phase, which can be used as a springboard
to cover important concepts related to interfacial tension,
hydrophilicity/hydrophobicity, hydration shells, and phase
transfer. Students found this lab to be informative, covering
new exciting avenues, and enjoyable. Instructors from the three
different institutions found this lab to be safe, short (total of 3
hours with the theoretical lecture introduction), cost-effective
(∼$1.4/student; see Table S1 for details), and highly
reproducible. Collectively, we believe that this laboratory is
suitable as an educational exercise that can be implemented in
chemistry or possibly physics curricula related to the emerging
field of nanoscience.
■
*
ASSOCIATED CONTENT
S Supporting Information
The Supporting Information is available on the ACS
Publications website at DOI: 10.1021/acs.jchemed.6b01003.
Instructor lab manual, template of student lab report,
template of student homework, template of student
feedback sheets, and selected samples of student lab
reports (PDF, DOCX)
Taped demonstration in video format (MPG)
773
■
Laboratory Experiment
AUTHOR INFORMATION
Corresponding Author
*E-mail: a.alkilany@ju.edu.jo.
ORCID
Alaaldin M. Alkilany: 0000-0001-9004-7256
Beatriz Pelaz: 0000-0002-4626-4576
Wolfgang J. Parak: 0000-0003-1672-6650
Catherine J. Murphy: 0000-0001-7066-5575
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
The authors acknowledge the funding support by Scientific
Research Fund-Jordan and Erasmus Mundus Mobility Award
for A.M.A. Part of this work was funded by the European
Commission (Grant FutureNanoNeeds to W.J.P.). M.G.S.
acknowledges funding from the FAZIT-Stiftung Germany. The
concept of this lab class was tested within the master class
“Functional Materials” (summer semester 2016) at Fachbereich
Physik of Philipps Universität Marburg.
■
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774 DOI: 10.1021/acs.jchemed.6b01003

J. Chem. Educ. 2017, 94, 769−774