A UV-blocking polymer shell prevents one-photon photoreactions while allowing multi-photon processes in encapsulated upconverting nanoparticles

Article abstract of DOI:10.1002/anie.201305253

Sun block for nanoparticles: Unintentional photorelease triggered by UV light is a problem in photodynamic therapy. Encapsulating upconverting nanoparticles containing photoswitches in a UV-blocking amphiphilic polymer shuts down the one-photon process and only allows two-photon-driven photochemistry. Thus, UV light is blocked while NIR light can reach the nanoparticle core and trigger photorelease. Copyright

Full text of DOI:10.1002/anie.201305253

.
Angewandte
Communications
DOI: 10.1002/anie.201305253
Photoresponsive Nanoparticles
A UV-Blocking Polymer Shell Prevents One-Photon Photoreactions
while Allowing Multi-Photon Processes in Encapsulated Upconverting
Nanoparticles**
Tuoqi Wu, Madeleine Barker, Khaled M. Arafeh, John-Christopher Boyer, Carl-Johan Carling,
and Neil R. Branda*
The use of low-energy two-photon excitation to provide
information about where and when non-invasive photore-
lease[1–5] and photodynamic therapy (PDT)[6–9] processes
occur avoids the need for high-energy UV or visible light.
Although this is an effective way to activate photoresponsive
agents while minimizing damage to cells and increasing
penetration depth into tissue, it does not take into account
one serious issue—it does not eliminate the direct activation
by the one-photon process. This fact explains why, after
therapy, patients often need to avoid excessive exposure to
sunlight or ambient light for a period of time to reduce photo-
toxicity.[10] Avoiding unwanted photochemistry requires
a UV-selective filter to block the high-energy light reaching
the photoresponsive agent while still retaining the activation
by multi-photon processes using longer wavelength light.
Herein, we demonstrate an effective way to reduce the
access of ultraviolet light to photoresponsive compounds and
how they can still be activated by generating the necessary
high-energy light using near infrared (NIR) light and
upconverting nanoparticles (UCNPs). Our strategy is illus-
trated in Scheme 1 and takes advantage of lanthanide-doped
NaYF4 nanoparticles wrapped in a UV-blocking organic
polymer. A photochromic dithienylethene derivative is used
as a model to demonstrate our concept, which can be applied
to photorelease and other phototherapeutic processes.
these UCNPs can be used to perform photochemistry, release
small molecules, and turn ꢀonꢁ and ꢀoffꢁ fluorescent markers in
polymers, in solution and even in live organisms.[14–21] Most of
this work was done using photoresponsive dithienylethenes
(DTEs), which undergo ring-closing and ring-opening reac-
tions between two isomers when exposed to UV and visible
light, respectively.[22–24] Because they are relatively well
behaved and have different optical properties depending on
the isomer, they provide a versatile proof-of-principle model
to demonstrate our concept. The two systems (inorganic
nanoparticles and organic photoresponsive chromophores)
can be combined to generate 1o-NP (Scheme 1) in which the
DTE is anchored to the surface of the UCNPs using “click”
chemistry.[15,19]
On the right of Scheme 1 is our hybrid system. The
decorated nanoparticles (1o-NP) are wrapped in a polymer
shell composed of polyamide containing PEG chains, one of
which is terminated with a known UV-blocking compound.[25]
The completely assembled system (1o-NP-P1) has five
distinct layers. The UCNP lies at the core and acts as the
NIR-to-UV “light bulb”. It is surrounded by a layer of
photoresponsive DTEs, whose role is to report on the success
of the concept. The amphiphilic nature of the comb-shaped
polymer results in a hydrophobic layer, which stabilizes the
assembly, keeps the inner hydrophobic components away
from contact with water and ensures the photochemistry of
the DTE is maintained, surrounded by a hydrophilic layer as
a result of the two PEG chains that project away from the
nanoparticle and out into the aqueous environment. The
longer of the two PEG chains is terminated with the UV-
blocking hydroxy benzophenone,[25] which forms the final
UV-light-filtering layer. Because all the layers are transparent
to NIR light, this light can still reach the nanoparticle core
and be converted into blue and UV light, which will be
emitted back out to the photoresponsive layer to trigger the
ring-closing reaction. On the other hand, UV light should not
penetrate the outer layer. In this way, the multi-photon
process can be selectively used and any direct activation of the
photochromic DTE by ambient light should be minimized.
Details of all synthetic steps are provided in the Support-
ing Information. The key step is the assembly of the polymer
shell around the DTE-decorated nanoparticles (1o-NP). Two
separate polymers were used to encapsulate these surface
modified nanoparticles. The first (P1) contains the UV-
blocking compound, the other (P2) does not and is used as
a control for our studies. We used the encapsulation method
described by Raymo and co-workers[26] and recently used by
Monodispersed core–shell NaYF4 nanocrystals containing
trivalent Tm3+ and Yb3+ ions (NaYF4:TmYb) offer an
effective way to generate UV and visible light using NIR
light.[11–13] These UCNPs absorb several NIR photons
(980 nm) and convert them into emissions in the UV and
visible regions of the spectrum. We have already shown how
[*] T. Wu, M. Barker, K. M. Arafeh, J.-C. Boyer, C.-J. Carling,
Prof. N. R. Branda
Department of Chemistry and 4D LABS
Simon Fraser University
8888 University Drive, Burnaby, BC V5A 1S6 (Canada)
E-mail: nbranda@sfu.ca
[**] This research was supported by the Natural Sciences and Engi-
neering Research Council (NSERC) of Canada, the Canada Research
Chairs Program and Simon Fraser University. This work made use of
4D LABS shared facilities supported by the Canada Foundation for
Innovation (CFI), British Columbia Knowledge Development Fund
(BCKDF), and Simon Fraser University. J.-C.B. thanks the Michael
Smith Foundation for Health Research (MSFHR) for financial
support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201305253.
11106
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 11106 –11109

Angewandte
Chemie
Scheme 1. Left: The reversible photo-induced ring-closing and ring-opening of photochromic dithienylethenes on the surface of lanthanide-doped
NaYF4 nanoparticles (1o-NP) using ultraviolet and visible light. The two polymers (P1 and P2) used to wrap the nanoparticles and the UV-blocker
(3) are also shown. Right: The direct ring-closing reaction using UV light is minimized while retaining the NIR-to-UV upconverting process. The
schematic representation on the far right show the relative length the polymers P1 and P2 extending from the nanoparticle surface starting from
the disuccinic diamide.
us[21] and others[27–29] to assemble the two final water-
dispersible systems (1o-NP-P1 and 1o-NP-P2). Transmission
electron microscopy showed these two nano-systems have an
average size of 29 nm.[30]
stop after a few minutes when the photostationary states are
reached. We assume that these states contain the same 72%
of the ring-closed isomer 1c based on the analysis of the
As is typical for dithienylethenes, the photoresponsive
derivative anchored to the nanoparticles in both nanoparticle
systems (1o-NP-P1 and 1o-NP-P2) undergo photochemical
reactions that are easily monitored by examining the UV/Vis
absorption spectra when solutions of them are irradiated with
UV light. As shown in Figure 1a, the ring-open isomer has no
absorption bands in the visible region. Exposing aqueous
solutions of either nano-system to 365 nm light causes
significant changes in the spectra. The high-energy absorption
bands decrease in intensity and new broad absorptions appear
in the visible region of the spectra, which accounts for the
change in the color of the solutions from colorless to blue.
Based on these changes in absorption, the ratio of “blue
filter” 3 to the photoresponsive dithienylethene 1o/c can be
estimated to be 2:1.[30]
Figure 1. a) UV/Vis absorption spectra of H2O solutions of top: 1o-
NP-P1 (3.4ꢀ10À6 m)[31] and bottom: 1o-NP-P2 (1.3ꢀ10À6 m)[31] before
(solid lines) and after irradiation with 365 nm light (broken lines). The
gray shaded area in each absorption spectrum corresponds to the
absorption of a CH3CN solution of the UV-blocker 3 (1.0ꢀ10À4 m) to
highlight the spectral overlap. b) Luminescent spectra of top: sunlight
measured for a typical day. Middle: the 365 nm UV light source used
for these studies, and bottom: the absorbance spectrum of 3.
The DTE in 1o-NP-P1 and 1o-NP-P2 have the same
optical behavior as the free chromophore in organic solvent
showing that there are no major changes when the compound
is encapsulated in the nano-system.[30] The spectral changes
Angew. Chem. Int. Ed. 2013, 52, 11106 –11109
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 11107

.
Angewandte
Communications
photostationary state for the free compound (1o/1c) by
1H NMR spectroscopy.
(Figure 2).[30] This simple experiment demonstrates the suc-
cess of our concept. Exposure to this NIR light resulted in no
changes in the absorption spectra for either system even after
12 h of continuous irradiation. Sunlight also resulted in no
observable degradation. Interestingly, neither 1o-NP-P1 nor
1o-NP-P2 are effected by typical indoor lighting (fluores-
cence or halogen).[30] When the emission spectra are exam-
ined the explanation is clear. Neither light source has a UV
component intense enough to trigger the ring-closing reac-
tion.
Figure 1a also shows how the absorption spectrum of the
pure “blue filter” (3) overlaps with the absorption bands for
the ring-open isomer of the photoresponsive dithienylethene
and illustrates how it can potentially act to block the UV light
from reaching the chromophores anchored to the nano-
particles. This “filter” should effectively reduce the amount of
light coming from the sun (Figure 1b) and prevent the one-
photon excitation of the DTE.
Figure 2 illustrates how the nano-system containing the
“blue filter” (1o-NP-P1) selectively blocks the UV light from
In conclusion, we have designed a water-dispersible nano-
system that undergoes multi-photon driven photochemistry
when exposed to 980 nm NIR light because this light can
penetrate the UV-blocking shell and turn on the upconverting
nanoparticle “light bulb”, while minimizing direct activation
with UV light. We believe that our nano-system will offer
a heightened level of control over photochemistry in many
applications.
Received: June 18, 2013
Published online: August 23, 2013
Keywords: multi-photon excitation · nanoparticles ·
.
photoswitches · upconversion · UV-blocking polymers
Figure 2. Absorption values at 590 nm for nanoparticles 1o/c-NP-
P1 (dark shaded) and 1o/c-NP-P2 (light shaded) when exposed to
different light sources. The values for sun light and NIR light are
average values from three separate measurements. The solar-UV
simulation conditions employ a 365 nm light source placed at a dis-
tance that matches the emission intensity of the UV component in
sunlight. Exposure times are 2 min for solar-UV, 2 min for UV
(365 nm), 2 min for outdoor sunlight and 30 min for 980 nm light.
[1] C. Brieke, F. Rohrbach, A. Gottschalk, G. Mayer, A. Heckel,
Angew. Chem. 2012, 124, 8572 – 8604; Angew. Chem. Int. Ed.
2012, 51, 8446 – 8476.
[2] F. Bolze, J.-F. Nicoud, C. Bourgogne, S. Gug, X. H. Sun, M.
Goeldner, A. Specht, L. Donato, D. Warther, G. F. Turi, A.
Losonczy, Opt. Mater. 2012, 34, 1664 – 1669.
[3] G. Ellis-Davies, Nat. Methods 2007, 4, 619 – 628.
[4] H.-M. Lee, D. R. Larson, D. S. Lawrence, ACS Chem. Biol. 2009,
4, 409 – 427.
[5] A. Specht, F. Bolze, Z. Omran, J. F. Nicoud, HFSP J. 2009, 3,
255 – 264.
[6] M. Gary-Bobo, Y. Mir, C. Rouxel, D. Brevet, I. Basile, M.
Maynadier, O. Vaillant, O. Mongin, M. Blanchard-Desce, A.
Morꢂre, M. Garcia, J.-O. Durand, L. Raehm, Angew. Chem.
2011, 123, 11627 – 11631; Angew. Chem. Int. Ed. 2011, 50, 11425 –
11429.
penetrating into the interior of the encapsulated nanoparti-
cles and activating the photoresponsive dithienylethenes.
When aqueous solutions of both systems (1o-NP-P1 and 1o-
NP-P2) are exposed to UV light (365 nm) from a hand-held
lamp at the distance that corresponds to the intensity of the
UV component in sun light,[32] the absorbance corresponding
to the ring-closed isomer (at 590 nm) appears to a significantly
lesser extent than it does for the nano-system without the
“blue filter” (1o-NP-P2). The basic photochemistry of the
dithienylethene is not affected since exposing both samples to
intense UV light (365 nm) saturates the filter and produces
the same intensity of the band at 590 nm. As expected from
these initial experiments, the same outcome results when the
two nano-systems are taken outdoors and exposed to sunlight
(Figure 2). Once again, the absorption corresponding to the
ring-closed isomer (1c) in 1o-NP-P1 is significantly reduced
in intensity when compared to that for 1o-NP-P2. These
differences are visually apparent. Colorless solutions of both
nano-systems turn dark blue when exposed to high intensity
UV light, however, only the system lacking the “blue filter”
(1o-NP-P2) turns deep blue when exposed to sun light.[30]
The multi-photon process of the UCNPs is not affected by
the presence of the ꢀblue filterꢁ and the photochemical ring-
closing of the DTE chromophore occurs equally for both 1o-
NP-P1 and 1o-NP-P2 when they are exposed to 980 nm light
[7] X. Shen, L. Li, H. Wu, S. Q. Yao, Q.-H. Xu, Nanoscale 2011, 3,
5140 – 5146.
[8] T. Zhao, X. Shen, L. Li, Z. Guan, N. Gao, P. Yuan, S. Q. Yao, Q.-
H. Xu, G. Q. Xu, Nanoscale 2012, 4, 7712 – 7719.
[9] G. Garcia, F. Hammerer, F. Poyer, S. Achelle, M.-P. Teulade-
Fichou, P. Maillard, Bioorg. Med. Chem. 2013, 21, 153 – 165.
[10] M. Triesscheijn, P. Baas, J. H. M. Schellens, F. A. Stewarta,
Oncologist 2006, 11, 1034 – 1044.
[11] Z. Q. Li, Y. Zhang, S. Jiang, Adv. Mater. 2008, 20, 4765 – 4769.
[12] F. Wang, Y. Han, C. S. Lim, Y. Lu, J. Wang, J. Xu, H. Chen, C.
Zhang, M. Hong, X. Liu, Nature 2010, 463, 1061 – 1065.
[13] X. Yea, J. E. Collins, Y. Kang, J. Chen, D. T. N. Chen, A. G.
Yodh, C. B. Murray, Proc. Natl. Acad. Sci. USA 2010, 107,
22430 – 22435.
[14] J.-C. Boyer, C.-J. Carling, B. D. Gates, N. R. Branda, J. Am.
Chem. Soc. 2010, 132, 15766 – 15772.
[15] C.-J. Carling, J.-C. Boyer, N. R. Branda, Org. Biomol. Chem.
2012, 10, 6159 – 6168.
[16] C.-J. Carling, F. Nourmohammadian, J.-C. Boyer, N. R. Branda,
Angew. Chem. 2010, 122, 3870 – 3873; Angew. Chem. Int. Ed.
2010, 49, 3782 – 3785.
11108 www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 11106 –11109

Angewandte
Chemie
[17] C.-J. Carling, J.-C. Boyer, N. R. Branda, J. Am. Chem. Soc. 2009,
131, 10838 – 10839.
[25] R. Herve, L. Florence, C. Didier, F. Cecile, PCT Int. Appl. WO
2011023886 A2 20110303, 2011.
[18] B. Yan, J.-C. Boyer, N. R. Branda, Y. Zhao, J. Am. Chem. Soc.
2011, 133, 19714 – 19717.
[19] J.-C. Boyer, C.-J. Carling, S. Y. Chua, D. Wilson, B. Johnsen, D.
Baillie, N. R. Branda, Chem. Eur. J. 2012, 18, 3122 – 3126.
[20] B. Yan, J.-C. Boyer, D. Habault, N. R. Branda, Y. Zhao, J. Am.
Chem. Soc. 2012, 134, 16558 – 16561.
[26] I. Yildiz, S. Impellizzeri, E. Deniz, B. McCaughan, J. F. Callan,
F. M. Raymo, J. Am. Chem. Soc. 2011, 133, 871 – 879.
[27] C. Wang, L. Cheng, Z. Liu, Ther. Deliv. 2011, 2, 1235 – 1239.
[28] C. Wang, L. Cheng, Z. Liu, Biomaterials 2011, 32, 1110 – 1120.
[29] S. A. Dꢃaz, L. Giordano, J. C. Azcꢄrate, T. M. Jovin, E. A. Jares-
Erijman, J. Am. Chem. Soc. 2013, 135, 3208 – 3217.
[21] T. Wu, J.-C. Boyer, M. Barker, D. Wilson, N. R. Branda, Chem.
Mater. 2013, 25, 2495 – 2502.
[30] See Supporting Information for more details.
[31] All concentrations are those for the encapsulated chromophores
obtained using the concentrations of the ring-closed isomers at
their photostationary state (as measured by UV/Vis spectrosco-
py) divided by percentage of ring-closed isomers in this state (as
measured by 1H NMR spectroscopy).
[22] B. L. Feringa, Molecular Switches, Wiley-VCH, Weinheim, 2010.
[23] H. Tian, S. Yang, Chem. Soc. Rev. 2004, 33, 85 – 97.
[24] L. Ubaghs, D. Sud, N. R. Branda, Handbook in Thiophene-Based
Materials: Applications in Organic Electronics and Photonics,
Vol. 2 (Eds: I. D. Perepichka, D. Perepichka), Wiley, Chichester,
2009.
[32] This distance was measured to be 65 cm. See Supporting
Information for more details.
Angew. Chem. Int. Ed. 2013, 52, 11106 –11109
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 11109