Nanoscale Metal–Organic Layers for Deeply Penetrating X-ray-Induced Photodynamic Therapy

Article abstract of DOI:10.1002/anie.201704828

We report the rational design of metal–organic layers (MOLs) that are built from [Hf₆O₄(OH)₄(HCO₂)₆] secondary building units (SBUs) and Ir[bpy(ppy)₂]⁺- or [Ru(bpy)₃]<

Full text of DOI:10.1002/anie.201704828

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Accepted Article
Title: Nanoscale Metal-Organic Layers for Deeply Penetrating X-ray
Induced Photodynamic Therapy
Authors: Guangxu Lan, Kaiyuan Ni, Ruoyu Xu, Kuangda Lu, Zekai Lin,
Christina Chan, and Wenbin Lin
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201704828
Angew. Chem. 10.1002/ange.201704828
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Angewandte Chemie International Edition
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COMMUNICATION
Nanoscale Metal-Organic Layers for Deeply Penetrating X-ray
Induced Photodynamic Therapy
‡a
‡a
a
a
a
a
*a
Guangxu Lan , Kaiyuan Ni , Ruoyu Xu , Kuangda Lu , Zekai Lin , Christina Chan , and Wenbin Lin
Abstract: We report the rational design of metal-organic layers
MOLs) that are built from [Hf (OH) (HCO ] secondary building
] - or Ru(bpy)
SBUs would enable direct excitation of the PSs by X-rays to
achieve X-ray induced photodynamic therapy (X-PDT).[ Here
we report the rational design of two MOLs, composed of
26]
(
6
O
4
4
2 6
)
+
2+
units (SBUs) and Ir[bpy(ppy)
2
3
-derived tricarboxylate
+
2+
[
6 4 4 2 6 2 3
Hf O (OH) (HCO ) ] SBUs and Ir[bpy(ppy) ] - or Ru(bpy) -
ligands (Hf-BPY-Ir or Hf-BPY-Ru; bpy = 2,2’-bipyridine, ppy = 2-
derived tricarboxylate ligands, as potent PSs. The Hf-MOLs
achieve greatly enhanced PDT efficacy both in vitro and in vivo
upon X-ray irradiation.
phenylpyridine) and their applications in X-ray induced photodynamic
therapy (X-PDT) of colon cancer. Heavy Hf atoms in the SBUs
+
efficiently absorb X-rays and transfer energy to Ir[bpy(ppy)
2
]
or
2+
Ru(bpy)
3
moieties to induce PDT by generating reactive oxygen
Scheme 1. Synthesis of Hf-based MOLs and MOL-enabled X-PDT
to generate singlet oxygen.
species (ROS). The ability of X-rays to penetrate deeply into tissue
and efficient ROS diffusion through ultrathin 2-D MOLs (~1.2 nm)
enable highly effective X-PDT to afford superb anticancer efficacy.
3O2
1O2
Energy
By combining three intrinsically nontoxic components--a
photosensitizer (PS), light, and tissue oxygen--to generate
cytotoxic reactive oxygen species (ROS), particularly singlet
1
oxygen ( O
2
), photodynamic therapy (PDT) provides a highly
effective phototherapy against cancer.[1] Because ROS
indiscriminately kill both diseased and normal cells, it is critical to
selectively localize PSs in tumors in order to enhance PDT
efficiency and minimize collateral damage to normal tissues.[2-13]
We and others reported a series of porphyrin- and chlorin-based
nanoscale metal-organic frameworks (nMOFs) as PSs for
effective PDT.[14-19] Because the lifetime of ROS is short, it is not
feasible for all the species generated to diffuse out of the 3-D
structure of nMOFs to exert cytotoxicity on cellular organelles,
thus limiting the overall efficacy of PDT in vivo.
Hf-BPY-Ir MOL
=
Hf (µ -O) (µ -OH) (HCO ) (RCO )
6 3 4 3 4 2 6 2
6
Hf-BPY MOL
Hf-BPY-Ir and Hf-BPY-Ru MOLs were synthesized by a
postsynthetic metalation method. 4’,6’-dibenzoato-[2,2’-
bipyridine]-4-carboxylic acid (H BPY) was synthesized as shown
We hypothesized that the in vivo PDT efficacy of nMOFs could be
further improved by reducing the dimensionality to afford 2-D
metal-organic layers (MOLs) and exciting the MOLs with more
tissue-penetrating X-rays. We recently reported a new class of
tunable and functionalizable MOLs that are composed of
3
in Figure S1 (SI) and treated with HfCl in N,N-dimethylformamide
4
(DMF), formic acid, and water to afford Hf-BPY MOL as a white
precipitate, which was then washed twice with DMF and once with
ethanol. By optimizing the amounts of formic acid and H O, the
2
size of Hf-BPY could be controlled to a diameter of ~500 nm, as
verified by transmission electron microscopy (TEM) (Figure 1a).
2 2 2 2
Hf-BPY was treated with [Ir(ppy) Cl] /Ru(bpy) Cl to afford Hf-
BPY-Ir/Hf-BPY-Ru MOL as an orange/brown participate. Due to
the 2-D structure of Hf-BPY, the bpy coordination sites are highly
accessible, resulting in efficient metalation. The Ir and Ru
loadings were determined to be 67% and 59% for Hf-BPY-Ir and
Hf-BPY-Ru, respectively, as determined by Inductively Coupled
Plasma-Mass Spectrometry (ICP-MS).
[
Hf
6 4 4 2 6
O (OH) (HCO ) ] secondary building units (SBUs) and
[
20]
benzene-1,3,5-tribenzoate (BTB) bridging ligands.
The 2-D
structure of MOLs allows ROS to diffuse freely, thus presenting
an ideal platform for designing nanoscale PSs for efficient PDT.
+
Ir[bpy(ppy)
2
]
(bpy = 2,2’-bipyridine, ppy = 2-phenylpyridine)
2
+
1
and Ru(bpy)
quantum yields (
due to large Stoke shifts, they can only be excited with photons at
3
are two efficient PSs with the very high
O
2
) of 0.97 and 0.73, respectively.[21-23] However,

+
short wavelengths, ~355 nm for Ir[bpy(ppy)
Ru(bpy) . Such UV-Vis photons cannot penetrate human tissue
penetration depth <0.1 mm),
2
] and ~450 nm for
2
+
In Hf-BPY, each Hf cluster of 12-connectivity was capped by 6
6
3
[
24]
formate groups (three at the top and three at the bottom), leaving
the remaining six sites coordinated to 3-connected BPY ligands
(
which severely limits their
application in PDT. Our previous work demonstrated that a Hf-
based nMOF can absorb X-rays and transfer energy to
coordinated anthracene-based ligands to luminesce in the visible
to form
OH) (HCO
a
3,6-connected 2-D network of Hf
6 3 4 3
(μ -O) (μ -
4
2
)
6
(BPY) of kagome dual (kgd) topology (Scheme 1).
2
spectrum.[ We believe that coordination between Ir[bpy(ppy)
25]
] -
3
-derived tricarboxylate ligands and heavy Hf-based
+
High-resolution TEM (HRTEM) images of Hf-BPY, where Hf6
clusters appear as dark spots, and fast Fourier transform (FFT)
patterns (Figure 1b) of Hf-BPY were consistent with the kgd
topology. The distance between two adjacent dark spots in the
HRTEM was 2.0 nm, which matched the distance between two
adjacent SBUs. The powder X-ray diffraction (PXRD) pattern of
Hf-BPY was identical to that of the Hf-BTB MOL (Figure 2a),[
which further confirmed the kgd structure of Hf-BPY. Atomic force
microscopy (AFM) images (Figure 1e, 1f and S13) of Hf-BPY
showed a 1.2 nm thickness, which is very close to the van der
2
2
+
or Ru(bpy)
[
a]
G. Lan, K. Ni, R. Xu, Dr. K. Lu, Z. Lin, C. Chan and Prof. W. Lin
Department of Chemistry, The University of Chicago
20]
929 East 57th street, Chicago, Illinois 60637, United States
E-mail: wenbinlin@uchicago.edu
These authors contributed equally to this work.
[‡
]
Supporting information for this article is given via a link at the end of
the document.
6
Waals size of the Hf cluster capped by formate groups, indicating
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Angewandte Chemie International Edition
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COMMUNICATION
the monolayer structure of Hf-BPY. A nitrogen sorption study of
Hf-BPY gave a BET surface are of 346 m /g (Figure S15),
S20-S23). Due to similar energy between Ir L
and Hf L -dege (11271 eV), XAS data was collected for Zr-BPY-
Ir instead of Hf-BPY-Ir.
3
-edge (11215 eV)
2
1
indicating its porous structure. The ultrathin monolayer structure
1
facilitates the diffusion of O
2
as its diffusion length was estimated
to be 20-220 nm in cells.[27]
We next examined singlet oxygen generation efficiencies of
MOLs using 4-nitroso-N,N-dimethylanaline (RNO) assay. We also
synthesized Zr-MOLs (Zr-BPY-Ir and Zr-BPY-Ru) using similar
processes (Figure S11 and S12) and used them for comparison.
a)
b)
Upon irradiation with a Xe lamp using a 400 nm long-pass filter or
1
X-rays (225 KVp, 13 mA), the O
2
generated by MOLs reacted
with RNO in the presence of histidine, leading to a decrease of
absorbance at 440 nm in the UV-visible spectra (Figure S24 and
S25). By linearly fitting difference in RNO peak absorbance
[
(OD)] against irradiation doses (which scale linearly with
exposure times upon visible light or X-ray dose, Y = Ax + B), the
RNO assay provides a quantitative measure of 1
generation
efficiencies, with a more positive slope indicating more efficient
O
2
1
2
O generation. Upon visible light irradiation, the linear fitting
1
results showed that Ir-based Zr- and Hf-MOLs generated
O
2
more efficiently than Ru-based Zr- and Hf-MOLs (Figures 2c,
c)
d)
1
Table S3), consistent with the difference in
O
2
generation
+
quantum yields between [Ir(bpy)(ppy)
Ru(bpy)
]2+ (
were observed between two Ir-based MOLs (A = 1.0910 for Hf-
2
]
( = 0.97) and

[
3

= 0.73). Furthermore, only very slight differences
-2
-2
BPY-Ir and A = 0.8810 for Zr-BPY-Ir) or two Ru-based MOLs
(
A = 4.110-3 for Hf-BPY-Ru and A = 2.410-3 for Zr-BPY-Ru),
1
suggesting minor effects of the SBUs in the
2
O generation
efficiency through spin-orbit coupling.[
14, 28]
The efficient singlet
oxygen generation by Hf-BPY-Ir upon light irradiation was also
demonstrated by Singlet Oxygen Sensor Green (SOSG) assay
(
Figure S26). Comparisons with DBP-Hf, a porphyrin-based
nMOF reported by us previously, indicated that Hf-BPY-Ir is more
effective in generating 1
O than DBP-Hf upon light irradiation
2
e)
f)
(
Figure S27), suggesting the facile diffusion of ROS through the
MOL monolayer.
a)
b)
H
H
H
BPY
Hf-BPY-Ru
Hf-BPY-Ir
Hf-BPY
3
3
3
BPY-Ir
BPY-Ru
Hf-BTB
Hf-BPY
Hf-BPY-Ir
Hf-BPY-Ru
Figure 1. Morphology and structure of Hf-based MOLs. TEM image (a), HRTEM
image, and FFT pattern (b) of Hf-BPY. TEM images of Hf-BPY-Ir (c) and Hf-
BPY-Ru (d). Tapping-mode AFM topography (e) and the height profile along the
white line (f) of Hf-BPY.
0
10
20
30 350
400
450
500
550
600
2
Wavelength (nm)
c)
d)
0.1
Hf-BPY-Ir
Hf-BPY-Ru
Zr-BPY-Ir
Hf-BPY-Ir
Hf-BPY-Ru
Zr-BPY-Ir
Zr-BPY-Ru
0
.1
TEM imaging showed that Hf-BPY-Ir (Figure 1c) and Hf-BPY-
Ru (Figure 1d) have similar morphologies and sizes as Hf-BPY.
The retention of the MOL structure after metalation was supported
by the similarity among the PXRD patterns of Hf-BPY-Ir, Hf-BPY-
Ru, and Hf-BPY (Figure 2a). In addition, the HRTEM images and
FFT patterns of Hf-BPY-Ir and Hf-BPY-Ru (Figure S10) were
identical to those of Hf-BPY. TEM images and PXRD patterns of
the MOLs remained unchanged after incubation in DMEM media
for 12 h (Figures S16 and 17), suggesting that the MOLs are
stable for biomedical applications.
Zr-BPY-Ru
0
.0
0.0
0
2
4
6
8
10
0
2
4
6
8
Time (min)
X-ray dose (Gy)
Figure 2. (a) PXRD patterns of new Hf-MOLs and the Hf-BTB MOL. (b) UV-
visible absorption spectra of Hf-MOLs and the bridging ligands. Singlet oxygen
generation of Hf- and Zr-MOLs upon visible light irradiation (c) or X-ray
irradiation (d), as determined by RNO. Linear fit of (OD) at 440 nm against
irradiation dose.
To further confirm the metalation of Hf-BPY and to understand
the coordination environments of Ir and Ru centers in Hf-MOLs,
we
(H
synthesized
BPY)Ru(bpy) ]Cl
[(H
3
BPY)Ir(ppy)
2
]Cl
(H
3
BPY-Ir)
and
However, upon X-ray irradiation, there was a drastic difference
[
3
2
2
3
(H BPY-Ru) as ligand controls (Figure S6-
in 1
O generation efficiencies in Zr- and Hf-MOLs (Figure 2d,
2
S9). The UV-visible absorption spectra of Hf-based MOLs exhibit
similar MLCT bands as their corresponding ligands (Figure 2b).
Importantly, X-ray absorption spectroscopy (XAS) indicated that
Zr-BPY-Ir and Hf-BPY-Ru have the same Ir and Ru coordination
-2
Table S4). Both Hf-MOLs (A = 1.2210 for Hf-BPY-Ir and A =
1
1
.010-2 for Hf-BPY-Ru) possessed much higher O
efficiency than their corresponding Zr-MOLs (A = 0.3910 for Hf-
BPY-Ir and
0.1910-2 for Zr-BPY-Ir), supporting our
hypothesis that the X-ray energy was first absorbed by SBUs and
2
generation
-2
environments as H
3
BPY-Ir and H
3
BPY-Ru, respectively (Figure
A =
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Angewandte Chemie International Edition
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COMMUNICATION
then transferred to the PSs in the bridging ligands to lead to the
X-PDT effect. Because the heavier Hf atoms absorb X-rays more
efficiently than the Zr atoms, the Hf-MOLs are expected to be
more effective at X-PDT. Additionally, Ir-based MOLs showed
only slightly better X-PDT efficiency than Ru-based MOLs,
suggesting different energy transfer processes involved in X-PDT
and PDT.
in thickness during X-ray irradiation (Figure S41). In contrast, light
induced cytotoxicity of Hf-BPY-Ir and Hf-BPY-Ru was completely
lost when the cells were covered with the same beef block during
light irradiation (Figure S40). These results support our
hypothesis that MOL-mediated X-PDT can be used to treat deep-
seated tumors. Interestingly, control experiments with Hf-QPDC-
6 3 4 3 4
Ir nMOF, a UiO nMOF built from Hf (μ -O) (μ -OH) SBUs and
QPDC-Ir bridging ligands, further support the enhanced X-PDT
efficacy of the MOLs due to facile ROS diffusion; upon X-ray
irradiation, Hf-QPDC-Ir nMOF exhibited much higher IC50 values
of 32.85 ± 3.02μM for CT26 cells and 26.08 ± 2.38 μM for MC38
cells, respectively (Figure S39).
In the clinic, PDT is typically applied to superficial malignant
tumors such as skin lesions and esophageal cancer due to the
limited penetration of light (~3 mm at 800 nm). We sought to
examine the potential of MOL-mediated X-PDT in the treatment
of deeply seated tumors. Two types of murine colon
adenocarcinoma cells, CT26 and MC38, were used for in vitro and
in vivo studies. The cellular uptake was evaluated on CT26 cells
incubated with Hf-BPY-Ir, Hf-BPY-Ru, or Hf-BPY at a Hf
concentration of 50 μM for 1, 4, 8, and 24 h. At each time point,
cells were digested and the Hf contents were determined by ICP-
We then explored the mechanism of X-ray induced cytotoxicity
on CT26 cells. 1
O
generation in live cells was examined by
SOSG and detected by confocal laser scanning microscopy
CLSM) (Figure S31). After preloading cells with SOSG and
incubating them with PBS, Hf-MOLs, or H BPY ligand for 8 h at a
2
(
3
5
concentration of 20 µM based on Ir, Ru, or BPY, respectively, they
were irradiated with X-rays at a dose of 2 Gy, immediately
followed by CLSM imaging. Both Hf-BPY-Ir- and Hf-BPY-Ru-
MS. Hf-BPY-Ru showed higher uptake (6580 ± 1770 ng/10 cells)
5
than Hf-BPY-Ir (3317 ± 665 ng/10 cells) and Hf-BPY (1930 ± 716
5
ng/10 cells), presumably because of the higher positive charge
treated cells showed strong green SOSG fluorescence, indicating
of Hf-BPY-Ru, which favors interacting with the negatively
charged cell membrane to facilitate endocytosis (Figure S28).
1
the efficient generation of O
2
in the MOLs upon X-ray irradiation.
BPY ligand-treated groups
showed no SOSG signal after X-ray induced 1
generation,
which supported our proposed X-PDT process using Hf-BPY-Ir
and Hf-BPY-Ru MOLs. We also performed -H AFX assay (Life
In contrast, PBS, Hf-BPY and H
3
a)
b)150
Hf-BPY-Ir (+)
Hf-BPY (+)
Zr-BPY-Ru (+)
Hf-BPY-Ru (+)
Zr-BPY-Ir (+)
Zr-BPY (+)
Hf-BPY-Ir (+)
Hf-BPY (+)
Zr-BPY-Ru (+)
Hf-BPY-Ru (+)
Zr-BPY-Ir (+)
Zr-BPY (+)
1
50
20
O
2
120
1
2
9
0
90
60
30
0
technology, USA) on CT26 cells to determine DNA double-strand
breaks (DSBs) caused by MOLs upon X-ray irradiation. As shown
in Figure S37, CT26 cells treated with three Hf-based MOLs
showed significant red fluorescence, indicating DSBs induced by
hydroxyl radical from X-ray irradiation. This result suggests that
60
30
0
0
20
40
60
80
100
0
20
40
60
80
100
Concentration (M)
Concentration (M)
6
Hf SBUs are capable of radiosensitization to further enhance
cytotoxicity of MOL-mediated X-PDT.
c) 2.4
d) 1
.8
.2
.6
Hf-BPY-Ir (+)
Hf-BPY-Ir (+)
Hf-BPY-Ru (+)
Hf-BPY (+)
PBS (+)
Hf-BPY-Ru (+)
Hf-BPY (+)
PBS (+)
1
1
0
0
.8
.2
.6
.0
Encouraged by in vitro results, we carried out in vivo anticancer
efficacy experiments on subcutaneous flank tumor-bearing
mouse models of CT26 and MC38. When tumors reached 100-
1
0
PBS (-)
PBS (-)
1
50 mm3 in volume, Hf-BPY-Ir, Hf-BPY-Ru, or Hf-BPY with
amount of 0.5 nmol based on Ir, Ru or BPY, respectively, or PBS
was intratumorally injected followed by daily X-ray irradiation at a
dose of 1 Gy/fraction (120 kVp, 20 mA, 2 mm-Cu filter) for a total
of 5 fractions on the CT26 model (Figure 3c) or 10 fractions on
the MC38 model (Figure 3d) on consecutive days. Tumor sizes
and body weights were measured every day. All mice were
sacrificed 18 days after tumor inoculation, and the excised tumors
were photographed and weighed (Figure S33-S34). To rule out
any radiotherapy effects from the low dose X-ray, we used PBS-
treated mice without X-ray irradiation as a dark control. The PBS
groups with or without irradiation did not show any difference in
tumor growth curves, indicating that low dose X-rays alone had
no radiotherapeutic effects. The Hf-BPY groups appeared to
show slight inhibition of tumor growth (P=0.047 or 0.048 for CT26
or MC38, respectively), consistent with the radiosensitization
0.0
0
2
4
6
8
10 12 14 16 18 20
0
2
4
6
8
10 12 14 16 18 20
Days Post Tumor Inoculation
Days Post Tumor Inoculation
Figure 3. In vitro and in vivo anticancer efficacy of Hf-MOLs. Cytotoxicity of Hf-
and Zr-MOLs in CT26 cells (a) and MC38 cells (b). Tumor growth inhibition
curves after X-PDT treatment in the CT26 (c) and MC38 (d) models. Black
arrows refer to injection of MOLs and red arrows refer to X-ray irradiation.
We next investigated the in vitro anticancer efficacy of three
different Hf-based MOLs against CT26 (Figure 3a) and MC38
(
Figure 3b) cells. To elucidate the key role of Hf in efficient
absorption of X-rays, three corresponding Zr-MOLs were used as
controls. MOLs were incubated with cells at various
concentrations for 8 h, followed by irradiation with an X-ray
irradiator at
a dose of 2 Gy. Hf-BPY-Ir and Hf-BPY-Ru
6
effects of the Hf SBUs. In stark contrast, Hf-BPY-Ir and Hf-BPY-
Ru treatments led to effective tumor regression in CT26 with 5
fractions of X-ray irradiation (5 Gy total; total volume reduction of
outperformed Hf-BPY and three Zr-MOLs. The IC50 values for Hf-
BPY-Ir, Hf-BPY-Ru, and Hf-BPY against CT26 cells were
calculated to be 3.82 ± 1.80, 3.63 ± 2.75, and 24.90 ± 7.87 μM,
respectively. Against MC38 cells, the IC50 values were 11.66 ±
8
3.6% or 77.3%, respectively) and in MC38 with 10 fractions of X-
ray irradiation (10 Gy; total total volume reduction of 82.3% or
0.1%, respectively). The weights and sizes of tumors treated
1.84, 10.72 ± 2.92, and 37.80 ± 6.57 μM, respectively. IC50 values
9
exceeded 100 μM for Zr-BPY-Ir, Zr-BPY-Ru, and Zr-BPY in both
CT26 and MC38 cell lines. No cytotoxicity was observed in dark
control groups (Figure S29). We also tested cell viability with fixed
Hf-MOL concentrations based on Ir, Ru, or BPY of 20µM,
with Hf-BPY-Ir and Hf-BPY-Ru at the end point were significantly
smaller than the other groups (Table S5 and S6). Histology of
frozen tumor slices confirmed MOL-assisted X-PDT caused
apoptosis/necrosis in tumors (Figure S35). No abnormalities were
observed on histological images of frozen organ slices, which
indicated that X-PDT with intratumoral injection of MOLs was not
systemically toxic (Figure S36). The lack of systemic toxicity was
further supported by steady body weights and similar weight gain
patterns in all groups (Figure S32).
respectively, and various X-ray doses (Figure S30). All of the
+
2
results showed greatly enhanced X-PDT potency of Ir[bpy(ppy) ]
2
+
and [Ru(bpy)
3
]
in Hf-MOLs. Importantly, X-ray induced
cytotoxicity of Hf-BPY-Ir and Hf-BPY-Ru remained essentially
unchanged when the cells were covered with a beef block of 1 cm
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COMMUNICATION
In summary, we rationally designed and synthesized two Hf-
MOLs as powerful PSs for effective X-PDT of colon cancer
models. Upon X-ray irradiation, Hf atoms in the SBUs absorb X-
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+
2+
rays and transfer energy to Ir[bpy(ppy)
2
] or [Ru(bpy)
, demonstrated by both RNO assay and in
detection as well as cytotoxicity studies. As a result of
3
]
in the
[
1
ligands to generate O
2
Oliveros, Helv. Chim. Acta 1996, 79, 1222.
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vitro O
deep tissue penetration of X-rays, high
2
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O
2
quantum yields of
+
2+
Ir[bpy(ppy) ] or [Ru(bpy) ] , and efficient ROS diffusion through
2
3
[26] H. Chen, G. D. Wang, Y.-J. Chuang, Z. Zhen, X. Chen, P. Biddinger, Z.
ultrathin MOLs, X-PDT treatment led to an impressive 90%
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Acknowledgements
We thank Dr. Chunbai He and Wenbo Han for experimental
help. We acknowledge the National Cancer Institute (U01–
CA198989), the University of Chicago Materials Research
Science and Engineering Center (DMR-1420709), the CBI
Training Grant (NIH 5T32GM008720-15), and the Ludwig
Institute for Metastasis Research for funding support. XAFS data
were collected at the APS at ANL on Beamline 10BM-A, B,
supported by the Materials Research Collaborative Access
Team (MRCAT). MRCAT operations are supported by the
Department of Energy and the MRCAT member institutions. This
research used resources of the Advanced Photon Source, a
U.S. Department of Energy (DOE) Office of Science User
Facility operated for the DOE Office of Science by Argonne
National Laboratory under Contract No. DE-AC02-06CH11357.
Keywords: Nanoscale Metal-Organic Layer • Photodynamic
Therapy • X-ray • Cancer Treatment•
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Angewandte Chemie International Edition
10.1002/anie.201704828
COMMUNICATION
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COMMUNICATION
X-ray induced PDT
Guangxu Lan, Kaiyuan Ni, Ruoyu Xu,
Kuangda Lu, Zekai Lin, Christina Chan,
and Wenbin Lin*
Heavy Hf atoms in the SBUs
efficiently absorb X-rays and transfer
energy to Ir[bpy(ppy)
moieties in ultrathin metal-organic
]+ or Ru(bpy)
2+
2 3
Page No. – Page No.
layers to induce PDT by generating
reactive oxygen species (ROS). Deep
Nanoscale Metal-Organic Layers for
Deeply Penetrating X-ray Induced
Photodynamic Therapy
1
tissue penetration of X-rays, high O
quantum yields, and efficient ROS
diffusion allow for regression of
2
colorectal tumors via MOL-mediated,
X-ray induced PDT treatments.
This article is protected by copyright. All rights reserved.