Materials Letters 237 (2019) 197–199
Contents lists available at ScienceDirect
Materials Letters journal homepage: www.elsevier.com/locate/mlblue
Controlled synthesis of [email protected]
core–shell structure for photodynamic therapy and magnetic resonance imaging Xuechuan Gao a,b, Guanfeng Ji a, Ruixue Cui a, Zhiliang Liu a,⇑ a b
College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, PR China College of Chemical Engineering, Inner Mongolia University of Technology, Hohhot 010051, PR China
a r t i c l e
i n f o
Article history: Received 9 September 2018 Received in revised form 12 November 2018 Accepted 16 November 2018 Available online 17 November 2018
a b s t r a c t For the first time, this work designs and constructs a fascinating [email protected]
core–shell structure, in which the inner Prussian blue (PB) can be used to magnetic resonance imaging and the outer Ti-MIL-125 can serve as photosensitive reagent for photodynamic therapy (PDT). In vitro cell experiments confirm that [email protected]
can induce cancer cells apoptosis obviously under ultraviolet illumination. Ó 2018 Published by Elsevier B.V.
Keywords: Metal–organic framework Photodynamic therapy Magnetic resonance imaging Biomaterials Multilayer structure
1. Introduction Photodynamic therapy (PDT) has received widespread attentions and gone through extensive explorations for tumor therapy [1,2]. PDT is a minimally invasive medical process in which a photosensitizer is used to interact with the surrounding oxygen molecules under light irradiation, generating reactive oxygen species (ROS). The ROS can induce serious oxidative damage to cancer cells and inhibit the growth of tumor tissue [3–5]. Constructed from metal ions and organic ligands, metal–organic frameworks (MOFs) have shown great potential in various fields [6–8]. The key feature of MOFs is their superior design flexibility, which make them suitable for PDT. For instance, Zhou et al. prepared size-controlled Zr (IV)-based porphyrinic MOFs for targeted PDT . Lin et al. reduced the 3D dimensionality of MOFs to 2D metal–organic layers (MOLs) which allowed ROS to diffuse freely . Although several MOFs have been studied for PDT, they usually have simple function that limits their practical applications. No previous study has reported on the incorporation of bioimaging and PDT into one platform based on MOFs. In this study, a novel [email protected]
core–shell structure is achieved for combining bioimaging and PDT into one particle. Ti-MIL-125 is a highly porous MOFs, assembled by tetravalent Ti4+ and terephthalic acid. Ti-MIL-125 displays satisfying ⇑ Corresponding author. E-mail address: [email protected]
(Z. Liu). https://doi.org/10.1016/j.matlet.2018.11.097 0167-577X/Ó 2018 Published by Elsevier B.V.
photoredox properties and has been proved to be good photoactive materials because of the reduction of TiIV to TiIII under UV irradiation . Ti-MIL-125 has potential applications in catalysis and appears to be a very attractive candidate to PDT [12,13]. Prussian blue (PB) was proved to be an effective magnetic resonance imaging (MRI) contrast agent, which is assembled by Fe3+ and 2-aminoterephthalic acid . Based on the above background, we have synthesized a [email protected]
core–shell structure (Fig. S1). As expected, the inner PB can present the satisfying relaxation rates for MRI and the outer Ti-MIL-125 can serve as photosensitive reagent for PDT. In vitro cell experiments confirm that [email protected]
can induce cancer cells apoptosis obviously under ultraviolet illumination. This work firstly provides a powerful tool to construct versatile MOFs for PDT and bioimaging successfully.
2. Results and discussion The SEM images and TEM images of PB and [email protected]
were shown in Fig. 1. Apparently, the as-prepared PB, shown in Fig. 1A and C, exhibits a typical cubic morphology with good dispersion and the average diameter of PB is around 100 nm. After coating with Ti-MIL-125, [email protected]
displays an obvious core–shell structure as shown in Fig. 1B and D. The shell thickness of [email protected]
is around 10 nm. Meanwhile, EDX mapping for [email protected]
have been done (Fig. S2). Evidently, the Fe element of PB is mainly distributed in the core and the Ti element is homogenously distributed in the outer layer. The crystallinity
X. Gao et al. / Materials Letters 237 (2019) 197–199
Fig. 1. SEM images (A) and TEM images (C) of PB; SEM images (B) and TEM images (D) of [email protected]
and purity of [email protected]
are further investigated by XRD. As expected, the XRD pattern of [email protected]
contains characteristic peaks of PB and Ti-MIL-125 (Fig. S3). Additionally, the diffraction peaks are strong and no other impure peaks can be found, confirming that [email protected]
with high purity is achieved successfully. The FTIR spectrum of [email protected]
is shown in Fig. S4C, which contains the characteristic vibration absorptions of PB and Ti-MIL-125. The peak at 2087 cm 1 is attributed to the vibrations of C–N in the FTIR spectrum of PB (Fig. S4A). The peak at 1395 cm 1 corresponds to the vibration absorption of benzene in Ti-MIL-125 (Fig. S4B). Simultaneously, the solid UV–vis absorption spectrum of [email protected]
exhibits characteristic absorptions of PB and Ti-MIL-125, as shown in Fig. S5. In Fig. S6, TGA curve of [email protected]
exhibits two obvious weight losses originated from PB and Ti-MIL-125 while TGA curve of PB displays only one distinct weight loss.
Fig. 2. Relaxation rate 1/T2 versus concentrations of [email protected]
; T2-weighted MRI of [email protected]
with diverse Fe concentrations in vitro (the insert).
Fig. 2 shows the relaxation rates, 1/T2, of [email protected]
as a function of Fe concentration. Evidently, relaxation rates increases linearly with increasing concentration of Fe and the [email protected]
presents a relatively modest value of transverse (r2) relaxivities (r2 = 14.51 m M 1 s 1), which implies that [email protected]
can be used as promising T2 MRI contrast agents. Besides, in vitro T2-weighted MRI of [email protected]
is shown in the insert of Fig. 2. It is visible that the signal intensity decreases (darkening) with the increase of the iron concentrations. Thus, [email protected]
has the potential to be used as MRI reagent for bioimaging. In order to study the in vitro efficacy of [email protected]
, the cell toxicity of [email protected]
was tested in HePG-2 cancer cells and HL-7702 normal cells. As shown in Fig. S7A and Fig. 3aA, more than 80% of HePG-2 cells and HL-7702 cells survived at a concentration of 200 lg/mL, confirming [email protected]
exhibits good biocompatibility. To demonstrate the PDT efficacy of [email protected]
, the cell inhibition of UV irradiation and [email protected]
under UV irradiation were tested. As shown in Fig. S7B and Fig. 3aB, under UV light exposure for 30 min, the HL-7702 cell viability is 85% while the HePG-2 cell viability is 62%. When the concentration of [email protected]
is 200 lg/mL, the HL-7702 cell viability after exposure to UV light for 30 min is 73% while the HePG-2 cell viability is 47% (Fig. S7C and Fig. 3aC). These results indicate that [email protected]
generates significant toxicity to cancer cells with UV irradiation. However, [email protected]
exhibits minor toxicity to normal cells with UV irradiation. The higher HePG-2 cell inhibition may be mainly attributed to the higher uptake of [email protected]
by cancer cells due to the more irregular cancer cell surface topography. When enter into the cancer cells, [email protected]
can generate super-oxide radical anion (O2 ) under UV irradiation. The generated super-oxide radical anion can damage cells and induce cell apoptosis. Meanwhile, the electron paramagnetic resonance (EPR) spectra of [email protected]
prove that the signal of super-oxide radical anion (O2 ) can be detected with UV irradiation, as shown in Fig. 3b. The process of [email protected]
to produce super-oxide radical anion can be inferred as follows. Upon irradiations, an electron can be transferred from the excited ligand to Ti–O oxo-clusters to
X. Gao et al. / Materials Letters 237 (2019) 197–199
Fig. 3. (a) Viabilities of HepG-2 cancer cells after being cultured with [email protected]
(A), after UV-irradiation for 30 min (B), after being cultured with [email protected]
and UV-irradiation for 30 min (C); (b) EPR spectra of DMPO-O2 adducts of [email protected]
in darkness and under visible light irradiation with different irradiation times.
form Ti3+ moiety. The as-formed Ti3+ can react with molecular oxygen to generate O2 while Ti3+ is oxidized back to Ti4+ . Thus [email protected]
is an ideal candidate for PDT. 3. Conclusion In this study, an interesting [email protected]
core–shell structure was obtained successfully, which integrates bioimaging and PDT into one platform for the first time. [email protected]
exhibits high transverse relaxivity and can be used as a contrast agent for magnetic resonance imaging. Additionally, [email protected]
can generate super-oxide radical anion under UV irradiation and induce cancer cell apoptosis. [email protected]
provides an excellent platform for achieving efficient PDT and bioimaging, broadening the practical applications of MOFs. Acknowledgements This work was supported by the Natural Science Foundation of China (21361016) and Inner Mongolia Autonomous Region Fund for Natural Science (2013ZD09). Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.matlet.2018.11.097. References  S.S. Kelkar, T.M. Reineke, Theranostics: combining imaging and therapy, Bioconj. Chem. 22 (2011) 1879–1903.
 X.H. Gao, Q. Yue, Z.N. Liu, M.J. Ke, X.Y. Zhou, S.H. Li, J.P. Zhang, R. Zhang, L. Chen, Y. Mao, Guiding brain-tumor surgery via blood–brain–barrier permeable gold nanoprobes with acid-triggered MRI/SERRS signals, Adv. Mater. 29 (2017) 1603917.  K. Lu, C. He, W. Lin, Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer, J. Am. Chem. Soc. 136 (2014) 16712–16715.  K. Lu, C. He, W. Lin, A chlorin-based nanoscale metal–organic framework for photodynamic therapy of colon cancers, J. Am. Chem. Soc. 137 (2015) 7600– 7603.  K. Lu, C. He, N. Guo, C. Chan, K. Ni, R.R. Weichselbaum, W. Lin, Chlorin-based nanoscale metal–organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy, J. Am. Chem. Soc. 138 (2016) 12502–12510.  J. Park, Q. Jiang, D. Feng, L. Mao, H. Zhou, Size-controlled synthesis of porphyrinic metal–organic framework and functionalization for targeted photodynamic therapy, J. Am. Chem. Soc. 138 (2016) 3518–3525.  M. Lismont, L. Dreesen, S. Wuttke, Metal–organic framework nanoparticles in photodynamic therapy: current status and perspectives, Adv. Funct. Mater. 27 (2017) 1606314.  J.J. Deng, K. Wang, M. Wang, P. Yu, L.Q. Mao, Mitochondria targeted nanoscale zeolitic imidazole framework-90 for ATP imaging in live cells, J. Am. Chem. Soc. 139 (2017) 5877–5882.  J. Park, Q. Jiang, D.W. Feng, L.Q. Mao, H.C. Zhou, Size-controlled synthesis of porphyrinic metal–organic framework and functionalization for targeted photodynamic therapy, J. Am. Chem. Soc. 138 (2016) 3518–3525.  G.X. Lan, K.Y. Ni, R.Y. Xu, K.D. Lu, Z.K. Lin, C. Chan, W.B. Lin, Nanoscale metal– organic layers for deeply penetrating X-ray-induced photodynamic therapy, Angew. Chem. Int. Ed. 56 (2017) 12102–12106.  R.M. Abdelhameed, O.M.H.M. Kamel, A. Amr, J. Rocha, A.M.S. Silva, Antimosquito activity of a titanium–organic framework supported on fabrics, ACS Appl. Mater. Interfaces 9 (2017) 29093–29100.  R.M. Abdelhameed, M.M.Q. Simões, A.M.S. Silva, J. Rocha, Enhanced photocatalytic activity of MIL-125 by post-synthetic modification with CrIII and Ag nanoparticles, Chem. Eur. J. 21 (2015) 11072–11081.  R.M. Abdelhameed, D.M. Tobaldi, M. Karmaoui, Engineering highly effective and stable nanocomposite photocatalyst based on NH2-MIL-125 encirclement with Ag3PO4 nanoparticles, J. Photochem. Photobiol. A: Chem. 351 (2018) 50– 58.  G. Zhao, J.J. Feng, Q.L. Zhang, S.P. Li, H.Y. Chen, Synthesis and characterization of Prussian blue modified magnetite nanoparticles and its application to the electrocatalytic reduction of H2O2, Chem. Mater. 17 (2005) 3154–3159.