Letter

Cite This: ACS Macro Lett. 2018, 7, 70−74 pubs.acs.org/macroletters

Simple and Green Strategy for the Synthesis of “Pathogen-Mimetic”

Glycoadjuvant@AuNPs by Combination of Photoinduced RAFT and
Bioinspired Dopamine Chemistry
Ming Wen, Mengjie Liu, Wentao Xue, Kai Yang, Gaojian Chen,* and Weidong Zhang*
Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University, Suzhou 215006, People’s Republic of
China
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, Suzhou 215123,
People’s Republic of China
*
S Supporting Information

ABSTRACT: Innate immune responses recognizing pathogen associ-

ated molecular patterns (PAMPs) play a crucial role in adaptive
immunity. Toll-like receptors (TLRs) and C-type lectin receptors
(CLRs) contribute to antigen capture, uptake, presentation and
activation of immune responses. In this contribution, metal-free
reversible addition−fragmentation chain transfer (RAFT) polymer-
ization of N-3,4-dihydroxybenzenethyl methacrylamide (DMA) and 2-
(methacrylamido) glucopyranose (MAG) under sunlight irradiation
using 2-cyanoprop-2-yl-α-dithionaphthalate (CPDN) as iniferter agent,
can be employed to fabricate the multivalent glycopolymer containing
bioresponsive sugar group and multifunctional catechol functionalities. The polymerization behavior is investigated and it
presents controlled features. Moreover, bioinspired dopamine chemistry can be successfully utilized to form in situ glycopolymer-
coated gold nanoparticles (AuNPs) without the need of additional reducing reagent, design “pathogen-mimetic” glycoadjuvant
recognized by both CLRs and TLRs. The synthetic glycoadjuvant is found to enhance the adjuvant activity as “infected signals” in
vitro.

Vaccine adjuvants can induce robust innate and adaptive
immunity and potentiate antigen-specific immune re-
sponses.1−3 Compared with traditional adjuvants such as
alum and mineral oil, unmethylated CpG adjuvants based on
pathogen-associated molecular patterns (PAMPs), a type of
Toll-like receptor 9 agonist, can mimic natural infections as
“danger signals”, activate professional antigen-presenting cells
(APCs), such as dendritic cells (DCs) and macrophages, and
elicit desired immune responses through recognition of pattern-
recognition receptors (PRRs) on APCs.1−3 CpG adjuvant can
trigger an APC maturation program, such as up-regulation of
MHC and costimulatory molecules, expression of pro-
inflammatory cytokines for inducing antigen-specific cytotoxic
T lymphocytes (CTLs) response.4−6 However, their clinical
uses as vaccine adjuvants are limited primarily due to lack of the
specific uptake by APCs and accumulation in the lymph nodes.7
Recently, we found that carbohydrate-functionalized adjuvants
(Dextran-CpG conjugate) markedly increased the uptake by
APC and retention in the lymph nodes and enhanced CD8+ T
cell responses, leading to improved therapeutic antitumor
immunity in vivo.8 In fact, carbohydrate-based materials acting
as important ligands for interacting with receptors on cell
surfaces play an important role in specific lectin/carbohydrate
biological processes such as cell−cell recognition and
communication.9,10 Pathogen recognition by C-type lectin
receptors (CLRs) expressed by DCs is important not only for
antigen presentation, but also for the induction of appropriate
adaptive immune responses.11 In addition, synthetic polymers
with pendent carbohydrate moieties called “glycopolymers”
possess good binding ability toward proteins, which are able to
interact with lectins in a similar manner to natural
glycoproteins.12−16 Indeed, CLR-binding carbohydrates are
potential therapeutic reagents for cancer immunotherapy.17,18
However, few reports have been conducted for designing
specific CLRs- and TLRs-targeted glycopolymer-based adju-
vant.
Polydopamine and dopamine derivatives inspired by the
adhesive proteins secreted by marine mussels have been used to
functionalize a wide array of material because molecules bearing
catechols are easily converted into highly reactive quinones,
which can further react with functional group, including thiols
and amines via Michael type addition or Schiff base
formation.19,20 For example, conjugation of DNA to polydop-
amine-coated substrates can be afforded through simple
immersion.21 However, the well-controlled catechol-containing
copolymers with predetermined chemical compositions is the
most challenging work. Generally, postpolymerization mod-
Received: October 26, 2017
Accepted: December 17, 2017
Published: December 20, 2017

© 2017 American Chemical Society 70 DOI: 10.1021/acsmacrolett.7b00837

ACS Macro Lett. 2018, 7, 70−74
ACS Macro Letters
ification and protected monomer strategies have been
employed to avoid the anticipated side reactions.22,23 We
have successfully developed the ambient temperature single
electron transfer and reversible addition−fragmentation (SET-
RAFT) method to prepare the well-defined dopamine-
containing copolymers, which shows excellent tolerance to
catechol groups.24 Moreover, based on this technique, well-
controlled glycopolymers bearing pendant catechols used as
versatile platforms for the further design of sugar-targeted
nanoparticles and surfaces, has been exploited for cellular
uptake and photodynamic therapy in vivo.14,25 It is noted that
the interaction between catechol groups and residual transition
metal catalysts is regarded as contamination for biomaterials
application.26 Indeed, copper(II) complexes could potentially
act as effective oxidants to accelerate the oxidation of catechol
groups.27
To overcome the challenge of metal contamination in SET-
RAFT polymerization, the photoinduced, metal-free RAFT
polymerization are developed.28−30 Recently, our group has
also developed the sunlight-induced RAFT polymerization
using typical RAFT agent as initiator and mediator at room
temperature,31 which is a good choice for preparing the
designed catechol-containing polymers. To develop “pathogen-
mimetic” glycoadjuvant that can exhibit high affinity and
selectivity toward pattern-recognition receptors, helping to
augment the immune response in the absence of infection, we
synthesized well-controlled glycopolymers carrying pendent
catechol moieties via RAFT copolymerization without photo-
catalyst (metal catalyst) and initiator at ambient temperature
(Scheme 1A). Then, using the versatile reactivity and redox
Scheme 1. (A) Fabrication of Glycopolymer by Metal-Free,
Sunlight-Induced RAFT; (B) Synthesis of “Pathogen-
Mimetic” Glycoadjuvant@AuNPs by Combination of
Photoinduced RAFT and Bioinspired Dopamine Chemistry
ability of the bioinspired catechol group, glycoadjuvant@Au
nanoparticles capable of mimicking the multivalent binding
activity and “danger signals” can be realized (Scheme 1B) in
aqueous conditions. In addition, TLR assay indicates
glycoadjuvant nanoparticles can potentiate its immunostimula-
tory activity in vitro.
Dopamine and its derivatives, acting as antioxidant agents,
have high activities in free radical scavenging.32 For instance,
tert-butylcatechol is largely employed as a polymerization
inhibitor. Therefore, traditional controlled radical copolymer-
ization (CRP) cannot obtain well-defined, mussel-inspired
polymers bearing pendant catechols, because side reactions and
71
Letter
inhibition cannot be avoided at relatively high temperatures
(Table 1). Although SET-RAFT technique opened up a new
Table 1. Copolymerization of DMA and MAG in DMSO
Using Different Techniques
temp time conv Mn(GPC)
entry method (°C) (h) (%) (g/mol) Mw/Mn
1a ATRP 80 24 12.2
2b RAFT 80 24 30.4
3c NMP 80 24 18.0
4d SET-RAFT 25 6 40.5 12300 1.36
5e photo-RAFT 25 20 54.8 16200 1.28
a1
[DMA]0/[MAG]0/[EBBr]0/[CuBr]0/[PMDETA]0 = 50:250:1:1:1.
b2
[DMA]0/[MAG]0/[CPDN]0/[AIBN]0 = 50:250:1:0.2. c3[DMA]0/
[MAG]0/[TEMPO]0/[BPO]0 = 50:250:1:1. d4[DMA]0/[MAG]0/
[EBBr] 0 : [CPDN] 0 /[Cu(0)] 0/[PMDETA]0 = 150:750:1:3:1:1.
e5
[DMA]0/[MAG]0/[CPDN]0 = 50:250:1.
avenue to effectively control the copolymerization of
dopamine-containing monomer, and no significant radical
coupling side reactions are observed,24 the application is
limited in the field of biomedical materials due to the specific
chelation with residual copper(II) ions (Cu2+). Visually, the
white glycopolymers powder obtained by SET-RAFT polymer-
ization of DMA and MAG (Figures S1 and S2), turned dark
brown in closed centrifuge tube for only 5 days due to the
reduction of Cu2+ ions (Figure S3), could not be dissolved in
common solvents, such as DMF, THF, or water. To avoid the
interference from residual Cu2+ ions, the sunlight-photolyzed,
metal-free RAFT polymerization are employed to prepare the
stable catechol-containing glycopolymers (entry 5 in Table 1).
Excellent control over molecular weight and a low molecular
weight distribution were observed. Moreover, control experi-
ment (Figure S3) indicated the oxidation of catechol-containing
glycopolymers prepared by photoinduced RAFT polymer-
ization could be ignored.
The typical simulated sunlight-induced RAFT copolymeriza-
tions of DMA and MAG were investigated systematically at
ambient temperature with CPDN as initiator, chain transfer
agent, and termination agent. To investigate the behavior of
polymerization, the 1H NMR spectra were employed to observe
the polymerization by monitoring the consumption of
monomer (Figure S4). As shown in Figure 1A, a linear
increase in ln([M]0/[M]) with exposure time was observed,
implying the copolymerization was a first-order kinetics with
respect to the monomer and with a constant number of active
species at the polymerization. It is noted that a significant
induction period of about 2 h was often observed, which could
be attributed to the time for establishing the equilibrium
between in situ activated radicals and CPDN31 or the inhibition
of catechol-containing monomer.24 Moreover, monomer
conversion increased linearly with exposure time during the
intermittent irradiations periods, and almost remained un-
changed in the absence of light as demonstrated in Figure 1B,
indicating sunlight-photolyzed RAFT process can be temporally
manipulated by on/off controls. The NMR results (Figure 1C)
revealed that sugar and dopamine are successfully integrated
into one polymer as verified with representative chemical shifts
at 4.9−5.6 and 6.5−7.0 ppm. In addition, based on the
corresponding integration values of i and j. g. h, the apparent
number-average molecular weight of PDMA 9-co-PMAG43
(Mn(NMR) = 12900 g/mol) was calculated. The composition
DOI: 10.1021/acsmacrolett.7b00837
ACS Macro Lett. 2018, 7, 70−74
ACS Macro Letters
Figure 1. (A) Kinetic plot of copolymerization of DMA and MAG in
DMSO solution at 25 °C. (B) ON/OFF controls for the sunlight-
activated RAFT copolymerization. (C) Typical 1H NMR spectrum of
glycopolymer, PDMA9-co-PMAG43 in D2O. (Mn(GPC) = 9200 g/mol,
Mn(NMR) = 12900 g/mol, Mw/Mn = 1.18). (D) GPC curve of
glycopolymer for the AuNPs (PDMA9-co-PMAG43).
of DMA and MAG is close to the feed ratio. On the other hand,
the GPC curve exhibiting sharp peak, confirmed a narrow
molecular weight distribution of obtained polymer (Mw/Mn =
1.18) with no significant side reactions (Figure 1D). Moreover,
an unsymmetrical peak with a tail toward the low molecular
weight was observed, which might be attributed to strong
interactions between dopamine-containing copolymer and
GPC column. These results strongly suggest that this metal-
free RAFT copolymerization of DMA and MAG can be
activated and deactivated by sunlight, enables control over the
molecular weight and molecular weight distributions, and
tolerates catechol and sugar groups.
It is well-known that self-polymerization of dopamine at basic
conditions is attributed to successive oxidation of catechol,
leading to the reducing activity and chelating ability offered by
the abundant catechol groups,33 and versatile reactivity
generated by highly reactive quinones.34 Here, the glycopol-
ymers (PDMA9-co-PMAG43) bearing catechols employing as
strong reducing agents should exhibit versatile the reducing
activity and chelating ability to modify the glycopolymers. The
time evolution of the absorption spectra indicated the catechol
groups were easly oxidized in the absence of basic conditions,
resulting in the corresponding glycopolymers bearing quinone
groups (Figure S5). This reactivity makes this polymer unique
and versatile for adjusting properties. On the other hand, in
light of the chelating ability of catechols, glycopolymer-coated
gold nanoparticles (glycopolymer@AuNPs) were also obtained
in situ by reduction of Au3+ without the need of any other
reducing reagent such as NaBH4, citrate, and ascorbate. The
UV−vis absorption spectra showed a maximum peak at about
540 nm attributed to the surface plasmon resonance band
(SPR) of the gold nanoparticles (Figure 2A). Moreover, the
band shifted toward lower wavelength as the quantity of
glycopolymers was increased. Furthermore, there was an
increase in the hydrodynamic diameter of the particles
following the addition of glycopolymers, indicating successful
immobilization of glycopolymers onto the gold surface (Figure
2B). From the TEM image (Figure 2D), the nonaggregation of
nanoparticles further confirmed that glycopolymer-coated
72
Letter
Figure 2. (A) UV−visible absorption spectra. (B) Dynamic light
scattering of glycopolymer-coated AuNPs. (C) Typical XPS spectra of
glycopolymer and glycopolymer-coated AuNPs. (D) TEM image of
glycopolymer-coated AuNPs.
AuNPs prepared by this strategy was quite stable. Besides,
further evidence could be obtained from the X-ray photo-
electron spectroscopy (XPS) spectra (Figure 2C). When the
glycopolymer was introduced to solution of HAuCl4, the signals
at 83.92 and 87.62 eV corresponding to the Au0 signal
appeared, implying the successful synthesis and stabilization of
gold nanoparticles using glycopolymer bearing catechols as
reducing agents. Meanwhile, strong C 1s and N 1s signals were
found, proving the presence of carbohydrate on the surface of
obtained glycoparticles. All of the above results demonstrated
that glycopolymer bearing catechols provide a green strategy
for preparing carbohydrate-functionalized AuNPs.
Herein, glycopolymer (PDMA9-co-PMAG43) bearing cat-
echols was utilized to reduce not only Au3+ giving rise to
carbohydrate-functionalized AuNPs, but also to react or bind
with thiol-terminal CpG capable of designing the glycoadju-
vant@AuNPs. The formation of glycoadjuvant@AuNPs was
confirmed by inhibition of CpG migration in gel electro-
phoresis (Figure S6). Moreover, the zeta potential (Figure S7)
and UV−vis absorption spectra (Figure S8) denoted CpG
conjugation was successfully achieved. Then, the adjuvant
activity of glycoadjuvant@AuNPs was assessed. RawBlue cells
are derived from murine Raw 264.7 macrophages, which can
express a wide variety of pattern recognition receptors. Upon
TLR or Dectin-1 (C-type lectin, which is the major receptor on
macrophages) stimulation, RawBlue cells express a secreted
embryonic alkaline phosphatase (SEAP), which is easily
qualitatively detectable using QUANTI-Blue as detection
medium. Interestingly, glycopolymer-coated AuNPs can
activate RAW-Blue cells (Figure 3), the possible reason is
mainly attributed to the fact that the aggregated NPs can
enhance the specific ligand−lectin (Dectin-1) binding
abilities.35,36 Comparable to unmodified CpG, glycoadju-
vant@AuNPs induced high levels of SEAP, indicating that
glycopolymer-modifited CpG adjuvant can improve the CpG’s
immune stimulatory activity.
To mimic immunogenic properties of natural pathogens,
photoactivated RAFT polymerization capable of fabricating
precise glycopolymer for interacting with C-type lectin
receptors on APC, and bioinspired catecholic chemistry
possessing the reducing and remodified abilities to conjugate
DOI: 10.1021/acsmacrolett.7b00837
ACS Macro Lett. 2018, 7, 70−74
ACS Macro Letters
Figure 3. (A) Illustration of SEAP levels expressed by RAWBlue cells;
(B) Immunostimulatory activities of glycopolymer-coated AuNPs,
glycoadjuvant@Au, and free CpG in RawBlue cells. Data show the
mean values ± SEM.
CpG adjuvant for “infected signals”, were for the first time
successfully integrated to design the “pathogen-mimetic”
glycoadjuvant@AuNPs. In addition, glycoadjuvant@AuNPs
can potentiate the adjuvant activity in vitro. We believe our
approach paves the way for the design and synthesis of the
glycoadjuvant to augment the immune cell activation.
■
*
ASSOCIATED CONTENT
S Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acsmacro-
lett.7b00837.
Experimental details and supporting figures (PDF).
■
AUTHOR INFORMATION
Corresponding Authors
*E-mail: zhangweidong@suda.edu.cn.
*E-mail: gchen@suda.edu.cn.
ORCID
Gaojian Chen: 0000-0002-5877-3159
Weidong Zhang: 0000-0002-6837-3060
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
The authors thank the Natural Science Foundation of Jiangsu
Province (No. BK20171208) and the National Natural Science
Foundation of China (No. 21774084) for financial support.
■ REFERENCES
(1) Liu, H.; Moynihan, K. D.; Zheng, Y.; Szeto, G. L.; Li, A. V.;
Huang, B.; Van Egeren, D. S.; Park, C.; Irvine, D. J. Structure-Based
Programming of Lymph-Node Targeting in Molecular Vaccines.
Nature 2014, 507, 519−522.
(2) Goldberg, M. S. Immunoengineering: How Nanotechnology Can
Enhance Cancer Immunotherapy. Cell 2015, 161, 201−204.
(3) Julier, Z.; De Titta, A.; Grimm, A. J.; Simeoni, E.; Swartz, M. A.;
Hubbell, J. A. Fibronectin EDA and CpG Synergize to Enhance
Antigen-Specific Th1 and Cytotoxic Responses. Vaccine 2016, 34,
2453−2459.
(4) Zhu, G.; Zhang, F.; Ni, Q.; Niu, G.; Chen, X. Efficient
Nanovaccine Delivery in Cancer Immunotherapy. ACS Nano 2017, 11,
2387−2392.
(5) Thomas, S. N.; Vokali, E.; Lund, A. W.; Hubbell, J. A.; Swartz, M.
A. Targeting the Tumor-Draining Lymph Node with Adjuvanted
Nanoparticles Reshapes the Anti-Tumor Immune Response. Bio-
materials 2014, 35, 814−824.
(6) Wang, C.; Li, P.; Liu, L.; Pan, H.; Li, H.; Cai, L.; Ma, Y. Self-
Adjuvanted Nanovaccine for Cancer Immunotherapy: Role of
73
Letter
Lysosomal Rupture-Induced ROS in MHC Class I Antigen
Presentation. Biomaterials 2016, 79, 88−100.
(7) Liu, H.; Irvine, D. J. Guiding Principles in the Design of
Molecular Bioconjugates for Vaccine Applications. Bioconjugate Chem.
2015, 26, 791−801.
(8) Zhang, W.; An, M.; Xi, J.; Liu, H. Targeting CpG Adjuvant to
Lymph Node via Dextran Conjugate Enhances Antitumor Immuno-
therapy. Bioconjugate Chem. 2017, 28, 1993−2000.
(9) Li, X.; Chen, G. Glycopolymer-Based Nanoparticles: Synthesis
and Application. Polym. Chem. 2015, 6, 1417−1430.
(10) Wu, L.; Zhang, Y.; Li, Z.; Yang, G.; Kochovski, Z.; Chen, G.;
Jiang, M. Sweet Architecture-Dependent Uptake of Glycocalyx-
Mimicking Nanoparticles Based on Biodegradable Aliphatic Polyesters
by Macrophages. J. Am. Chem. Soc. 2017, 139, 14684−14692.
(11) Lepenies, B.; Lee, J.; Sonkaria, S. Targeting C-type Lectin
Receptors with Multivalent Carbohydrate Ligands. Adv. Drug Delivery
Rev. 2013, 65, 1271−1281.
(12) Chen, Y.; Lord, M. S.; Piloni, A.; Stenzel, M. H. Correlation
Between Molecular Weight and Branch Structure of Glycopolymers
Stars and Their Binding to Lectins. Macromolecules 2015, 48, 346−
357.
(13) Becer, C. R.; Gibson, M. I.; Geng, J.; Ilyas, R.; Wallis, R.;
Mitchell, D. A.; Haddleton, D. M. High-Affinity Glycopolymer Binding
to Human DC-SIGN and Disruption of DC-SIGN Interactions with
HIV Envelope Glycoprotein. J. Am. Chem. Soc. 2010, 132, 15130−
15132.
(14) Li, X.; Bao, M.; Weng, Y.; Yang, K.; Zhang, W.; Chen, G.
Glycopolymer-Coated Iron Oxide Nanoparticles: Shape-Controlled
Synthesis and Cellular Uptake. J. Mater. Chem. B 2014, 2, 5569−5575.
(15) Miura, Y.; Hoshino, Y.; Seto, H. Glycopolymer Nano-
biotechnology. Chem. Rev. 2016, 116, 1673−1692.
(16) Sunasee, R.; Narain, R. Glycopolymers and Glyco-nanoparticles
in Biomolecular Recognition Processes and Vaccine Development.
Macromol. Biosci. 2013, 13, 9−27.
(17) Yan, H.; Kamiya, T.; Suabjakyong, P.; Tsuji, N. M. Targeting C-
Type Lectin Receptors for Cancer Immunity. Front. Immunol. 2015, 6,
408.
(18) Vang, K. B.; Safina, I.; Darrigues, E.; Nedosekin, D.; Nima, Z. A.;
Majeed, W.; Watanabe, F.; Kannarpady, G.; Kore, R. A.; Casciano, D.;
Zharov, V. P.; Griffin, R. J.; Dings, R. P. M.; Biris, A. S. Modifying
Dendritic Cell Activation with Plasmonic Nano Vectors. Sci. Rep.
2017, 7, 5513.
(19) Faure, E.; Falentin-Daudré, C.; Jérôme, C.; Lyskawa, J.;
Fournier, D.; Woisel, P.; Detrembleur, C. Catechols as Versatile
Platforms in Polymer Chemistry. Prog. Polym. Sci. 2013, 38, 236−270.
(20) Sedo, J.; Saiz-Poseu, J.; Busque, F.; Ruiz-Molina, D. Catechol-
Based Biomimetic Functional Materials. Adv. Mater. 2013, 25, 653−
701.
(21) Lee, H.; Rho, J.; Messersmith, P. B. Facile Conjugation of
Biomolecules onto Surfaces via Mussel Adhesive Protein Inspired
Coatings. Adv. Mater. 2009, 21, 431−434.
(22) Isakova, A.; Topham, P. D.; Sutherland, A. J. Controlled RAFT
Polymerization and Zinc Binding Performance of Catechol-Inspired
Homopolymers. Macromolecules 2014, 47, 2561−2568.
(23) Xu, L. Q.; Jiang, H.; Neoh, K.-G.; Kang, E.-T.; Fu, G. D.
Poly(dopamine acrylamide)-co-Poly(propargyl acrylamide)-Modified
Titanium Surfaces for ‘Click’ Functionalization. Polym. Chem. 2012, 3,
920.
(24) Wang, J.; Zhu, H.; Chen, G.; Hu, Z.; Weng, Y.; Wang, X.;
Zhang, W. Controlled Synthesis and Self-Assembly of Dopamine-
Containing Copolymer for Honeycomb-like Porous Hybrid Particles.
Macromol. Rapid Commun. 2014, 35, 1061−1067.
(25) Chen, K.; Bao, M.; Muñoz Bonilla, A.; Zhang, W.; Chen, G. A
Biomimicking and Electrostatic Self-Assembly Strategy for the
Preparation of Glycopolymer Decorated Photoactive Nanoparticles.
Polym. Chem. 2016, 7, 2565−2572.
(26) Zhang, Q.; Nurumbetov, G.; Simula, A.; Zhu, C.; Li, M.; Wilson,
P.; Kempe, K.; Yang, B.; Tao, L.; Haddleton, D. M. Synthesis of Well-
DOI: 10.1021/acsmacrolett.7b00837
ACS Macro Lett. 2018, 7, 70−74
ACS Macro Letters Letter

Defined Catechol Polymers for Surface Functionalization of Magnetic

Nanoparticles. Polym. Chem. 2016, 7, 7002−7010.
(27) Neves, A.; Rossi, L. M.; Bortoluzzi, A. J.; Szpoganicz, B.;
Wiezbicki, C.; Schwingel, E.; Haase, W.; Ostrovsky, S. Catecholase
Activity of a Series of Dicopper(II) Complexes with Variable Cu-
OH(phenol) Moieties. Inorg. Chem. 2002, 41, 1788−1794.
(28) Chen, M.; MacLeod, M. J.; Johnson, J. A. Visible-Light-
Controlled Living Radical Polymerization from a Trithiocarbonate
Iniferter Mediated by an Organic Photoredox Catalyst. ACS Macro
Lett. 2015, 4, 566−569.
(29) Yeow, J.; Sugita, O. R.; Boyer, C. Visible Light-Mediated
Polymerization-Induced Self-Assembly in the Absence of External
Catalyst or Initiator. ACS Macro Lett. 2016, 5, 558−564.
(30) McKenzie, T. G.; Costa, L. P.; da, M.; Fu, Q.; Dunstan, D. E.;
Qiao, G. G. Investigation into the photolytic stability of RAFT agents
and the implications for photopolymerization reactions. Polym. Chem.
2016, 7, 4246−4253.
(31) Wang, J.; Rivero, M.; Muñoz Bonilla, A.; Sanchez-Marcos, J.;
Xue, W.; Chen, G.; Zhang, W.; Zhu, X. Natural RAFT Polymerization:
Recyclable-Catalyst-Aided, Opened-to-Air, and Sunlight-Photolyzed
RAFT Polymerizations. ACS Macro Lett. 2016, 5, 1278−1282.
(32) Son, S.; Lewis, B. A. Free Radical Scavenging and Antioxidative
Activity of Caffeic Acid Amide and Ester Analogues: Structure-Activity
Relationship. J. Agric. Food Chem. 2002, 50, 468−472.
(33) Holten-Andersen, N.; Harrington, M. J.; Birkedal, H.; Lee, B. P.;
Messersmith, P. B.; Lee, K. Y. C.; Waite, J. H. pH-induced metal-ligand
cross-links inspired by mussel yield self-healing polymer networks with
near-covalent elastic moduli. Proc. Natl. Acad. Sci. U. S. A. 2011, 108,
2651−2655.
(34) Mrowczynski, R. Polydopamine-Based Multifunctional (Nano)-
materials for Cancer Therapy. ACS Appl. Mater. Interfaces 2017,
DOI: 10.1021/acsami.7b08392.
(35) Lu, J.; Zhang, W.; Richards, S.; Gibson, M.; Chen, G.
Glycopolymer-coated Gold Nanorods Synthesised by a One Pot
Copper(0) Catalyzed Tandem RAFT/Click Reaction. Polym. Chem.
2014, 5, 2326−2332.
(36) Ting, S. R. S.; Min, E. H.; Zetterlund, P. B.; Stenzel, M. H.
Controlled/Living ab Initio Emulsion Polymerization via a Glucose
RAFTstab: Degradable Cross-Linked Glyco-Particles for Concanavalin
A/FimH Conjugations to Cluster E. coli Bacteria. Macromolecules
2010, 43, 5211−5221.

74 DOI: 10.1021/acsmacrolett.7b00837
ACS Macro Lett. 2018, 7, 70−74