MetalâOrganic Frameworks-Derived Carbon Nanoparticles for

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Biological and Medical Applications of Materials and Interfaces

Metal-Organic Frameworks Derived Carbon Nanoparticles for Photoacoustic Imaging-Guided Photothermal/Photodynamic Combined Therapy Peng Yang, Ye Tian, Yongzhi Men, Ranran Guo, Haibao Peng, Qin Jiang, and Wuli Yang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b15828 • Publication Date (Web): 14 Nov 2018 Downloaded from http://pubs.acs.org on November 15, 2018

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ACS Applied Materials & Interfaces

Metal-Organic Frameworks Derived Carbon Nanoparticles for Photoacoustic Imaging-Guided Photothermal/Photodynamic Combined Therapy Peng Yang,† Ye Tian,‡ Yongzhi Men,§ Ranran Guo,† Haibao Peng,† Qin Jiang† and Wuli Yang*,† iD

†State

Key Laboratory of Molecular Engineering of Polymers and Department of

Macromolecular Science, Fudan University, Shanghai, 200433, China ‡Department

§Shanghai

of Chemistry, Stanford University, Stanford, CA 94305, United States

General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China

KEYWORDS:

metal-organic

framework,

carbon

nanoparticle,

photodynamic therapy, photoacoustic imaging

ACS Paragon Plus Environment

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photothermal

therapy,

ACS Applied Materials & Interfaces 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ABSTRACT: Combination of photothermal therapy (PTT) and photodynamic therapy (PDT) is a promising cancer treatment in recent years. However, their applications are limited by complex synthetic protocols and low-efficacy. Hence, optimizing experimental approach and improving efficiency of phototherapy is current research focus. In this work, various pyrolysis temperatures and sizes of zeolitic imidazolate framework-8 (ZIF-8) derived carbon nanoparticles (ZCNs) are obtained by a simply direct pyrolysis of ZIF-8 nanoparticles. Meanwhile, the ZCNs can be used as photothermal agents and photosensitizers to produce heat and reactive oxygen species simultaneously upon near infrared laser irradiation. Moreover, it is found out that the phototherapy effects and photoacoustic (PA) signal of ZCNs could be enhanced with the increase of nanoparticle size. Subsequently, guided by PA imaging, the therapeutic effect of ZCNs are investigated on a small animal model, where tumors are entirely eliminated with minimal side effect, demonstrating the high efficacy of larger size of ZCNs through combination of PTT and PDT. Therefore, it is expected that the ZCN is a simple and highly-effective phototherapeutic platform for oncotherapy, and the concept of size dependent enhanced behavior of phototherapy and PA imaging will be very useful in the development of nanomaterials for cancer therapy.


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1. INTRODUCTION Cancer is a highly complex disease and has become a major threat to human health for many years.1-2 In the clinic, the mainstream therapeutic options for cancer include surgical operation of tumor, chemotherapy, radiotherapy or their combined treatment. However, in many cases, these therapeutic regimens are not effective and have associated notorious side effects. Nowadays, many combined therapeutic methods are developed to improve the efficiency of cancer therapy. In these methods, phototherapy is an attractive way because of its minimally invasion, easy applicability, and low systemic toxicity and side effects.3-6 A major phototherapy system includes photothermal therapy (PTT) and photodynamic therapy (PDT), which employs photothermal conversion agents to transform optical energy to heat7 or utilizes photosensitizers to generate reactive oxygen species (ROS)8 to kill cancer cells under near infrared (NIR) laser irradiation. In recent years, several photothermal agents, including gold nanostructures,9-11 carbon nanomaterials,12-14 WS2,15 and MoS2 nanosheets,16 have been jointed with typical photosensitizer (PS) through surface modification and encapsulation to construct PTT and PDT combined therapies. While these systems have exhibited some advantages for cancer therapy, however their applications are limited by complex synthetic protocols and low-efficacy. Therefore, the types of cancer theranostics capable of simply, safely and efficiently simultaneous PTT and PDT are needed to expand the practical application of phototherapy. Metal-organic framework (MOF) nanomaterials have received tremendous attentions in many applications, such as gas separation and storage,17-19 catalysis,20-21 sensing,22 and drug delivery,2325

as their metal ions and organic linkers can be highly tailorable. Especially due to their

permanent nano-scale channels and cavities, MOFs exhibit a great potential as precursors for preparing carbon nanomaterials for lithium-ion batteries and catalytic applications.26-29 Most


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recently, carbon nanomaterials for photothermal therapy through pyrolysis of MOFs have attracted researcher's attentions,30 which are because of the distinct advantages of carbon nanomaterials.31-32 Meanwhile, many factors influence the efficiency of photothermal effects, such as size33-35 and morphology36-37 of nanoparticles. However, to the best of our knowledge, not only the enhanced photothermal effects, but also the improved combinated phototherapy effects induced by the increase of nanoparticle size have raraly been reported for carbon nanomaterials, which is very important to the blossom of carbon nanomaterials for phototherapy. Herein, we develop ZIF-8 derived carbon nanoparticles (ZCNs) through an economical onestep method to realize photoacoustic (PA) imaging guided cancer therapy, and the relationship between the nanoparticle size with the phototherapy effect and PA capability is investigated. The fabrication of ZCNs is elucidated in Scheme 1. Through a simply direct pyrolysis of ZIF-8 nanoparticles, the monodisperse ZCNs keep similar morphology with ZIF-8 nanoparticles. And the ZCNs can be used as photothermal agents and photosensitizers to realize combined photothermal and photodynamic therapy under NIR laser irradiation. Interestingly, we find that such ZCNs exhibit an enhanced phototherapy effects and PA signal with the increase of nanoparticle size. Meanwhile, the combined PDT and PTT effects with the increase of nanoparticle are also confirmed in vitro experiments. Furthermore, owing to the property of carbon nanomaterials,32, 38 the ZCNs can serve for photoacoustic imaging, which proves efficient tumor accumulation of ZCNS after intravenous injection. Importantly, the ZCNs can be used to ablate tumor under NIR laser irradiation and show low systemic toxicity and side effects. Our finding highlights that the nanoparticle size of ZCNs affect the phototherapy effect and PA signal intensity, which will open an avenue of structure-function relationship to design and develop novel materials with higher performances for cancer therapy.


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Scheme 1. Schematic diagram of preparation of ZIF-8 derived carbon nanoparticles (ZCNs) and their applications for in vivo PA imaging guided photothermal/photodynamic combined therapy.

2. EXPERIMENTAL SECTION 2.1 Chemicals and reagents. Zinc nitrate hexahydrate, 2-methylimidazole were ordered from Aladdin Company (Shanghai, China). Indocyanine green (ICG) and 1, 3-diphenylisobenzofuran (DPBF) were purchased from TCI Company (Shanghai, China). The biological reagents were purchased from Sigma Company (St. Louis, USA). All reagents used in this work were analytical grade (A.R.). A549 cells obtained from Chinese Academy of Sciences Cells Bank (Shanghai, China). Male Balb/c nude mice aged 4-5 weeks were purchased from BK Laboratory Animal Co. Ltd. All animal experiments were performed and approved under the Animal Ethics of Fudan University. To construct mice bearing A549 tumors models, approximately 1×106 A549 cells in 0.1 mL of PBS solution were injected subcutaneously into the right buttock of each male Balb/c nude


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mouse. The tumor volume was obtained by the following formula: V =d2 × D/2, where d, D is the width of tumor and the length of tumor, respectively. 2.2 Synthesis of ZIF-8 nanoparticles. ZIF-8 nanoparticles (200 nm) were prepared according to the published method with slight modification.39 Briefly, zinc nitrate hexahydrate (4 mmol) was dissolved in 20 mL methanol, to which 40 mL of methanol containing 40 mmol 2methylimidazole was dropped in, the mixture was stirred for 2 h at 40 oC. The white products were collected through centrifugation (9000 rpm, 15 min) and washed with methanol for several times. The 60 and 110 nm ZIF-8 nanoparticles were synthesized by the same method with the molar ratios of zinc nitrate hexahydrate and 2-methylimidazole are 2 : 20 and 3 : 30. 2.3 Synthesis of ZIF-8 derived carbon nanoparticles. ZIF-8 derived carbon nanoparticles (ZCNs) were prepared by direct pyrolysis (900 oC) of the ZIF-8 nanoparticles under a flow of nitrogen gas.28 Briefly, the ZIF-8 sample was homodispersed in ceramic boat. After exposed to nitrogen atmosphere (400 mL min-1) at room temperature for 30 min, the tube furnace was heated to 130 oC for 45 min to remove residual water. Then the furnace was heated to 900 oC with a temperature rate of 5 oC min-1 and pyrolysis for 3 h, and cooled slowly to room temperature. ZCNs were modified by mixing with monomethoxy poly(ethylene oxide)-distearoyl phosphatidyl ethanolamin (mPEG-DSPE, 5 kD) in CHCl3 solution and concentrated in vacuo to remove CHCl3 solution, followed by centrifugation (11000 rpm, 10 min) and washed with deionized water for several times. 2.4 Measurement of photothermal effects of ZCNs. To evaluate the photothermal effects, 200 μL (50 μg mL−1) ZCNs dispersion were dropped into a 96-well plate. Under illuminated 808 nm continuous-wave NIR laser, the temperature was obtained by an infrared camera.


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2.5 Measurement of singlet oxygen quantum-yield of ZCNs. The DPBF was used as 1O2 trapping probe and ICG was used as reference (1O2 quantum yield ΦICG 0.0020).30 In order to avoid inner-filter effects, the UV absorbance at 808 nm of ZCNs and ICG was adjusted to about 0.5 OD. Then, 50 µL 1O2 trapping probe DPBF was added into the ZCNs dispersion (1.5 mL) under NIR laser irradiation for different times. The photo-decomposition rate of DPBF was quantified by the change of UV absorbance at 419 nm. The detailed measurement of is descried in the Supporting Information. 2.6 Cytotoxicity assay. 293T cells and A549 cells were plated in 96-well culture plates for 24 h incubation. Subsequently, cells were treated with different concentrations of ZCNs dispersion and

incubated

for

24h.

Finally,

standard

the

3-(4,

5-dimethylthiazol-2-yl)-2,

5-

diphenyltetrazolium bromide (MTT) assay were used to measure the viability of cells. 2.7 In vitro PTT and PDT assay. A549 cells were seeded in 96-well plates for 24 h incubation, and the cells were treated with the ZCNs dispersion for 4 h to allow cellular uptake. Then, the cells in each plate were irradiated to a NIR laser (808 nm, 3 W cm−2, and 5 min). After 24 h incubation, standard MTT assay were used to measure the viability of cells. For the measurement of the efficacy of PDT, the in vitro phototherapy was conducted with the 96-well plates half-immersed in a 4 oC water bath to maintain a constant temperature. And for the measurement of PTT efficacy, the in vitro phototherapy was conducted in the presence of 100 mM NaN3 to scavenge the ROS generated in the therapeutic process. 2.8 In vitro and vivo PA imaging. For in vitro PA imaging, different concentrations of ZCNs are filled in the polyethylene tube, and then measured by the high resolution pre-clinical PA imaging system. ImageJ software are utilized to process the images.


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For in vivo PA imaging, mice bearing A549 tumors were injected 100 μL (2 mg mL-1) of ZCNs dispersion by intravenously. Subsequently, the PA signal at different time of ZCNs was captured by the high resolution pre-clinical PA imaging system. 2.9 In vivo phototherapy. A549 tumor-bearing mice were randomly separated into four groups, with 6 mice for each group: PBS with laser treated (Group 1), ZCN-110 (3 W cm-2, 5 min) with laser treated (Group 2), ZCN-200 (3 W cm-2, 5 min) with laser treated (Group 3), ZCN-200 (1 W cm-2, 10 min) with laser treated (Group 4). For group 2 and 3, 100 μL of nanoparticles (3 mg mL−1) were injected into mice by tail intravenous, then irradiated by 808 nm NIR laser (3 W cm−2, 5 min) after 4 and 6 h injection. And for group 4, after 6 h injection of ZCNs by tail intravenous (6 mg mL-1), the tumors were treated with an 808 nm NIR laser (1 W cm−2, 10 min). At 14th day, all of the mice were euthanized and the tumors and major organs (heart, liver, spleen, lung, and kidney) of mice were dissected and fixed in 4% formalin solution for tissue slices. 2.10 Statistical analysis. All data reported are mean result ± SD. The statistical analysis was conducted by unpaired student’s t-test, p < 0.05 was considered as statistical significance, and p < 0.01 was considered as very statistical significance. 3. RESULTS AND DISCUSSION 3.1 Preparation of ZIF-8 derived carbon nanoparticles ZIF-8 nanoparticles are prepared by directly mixing different molar radios of 2methylimidazole (2-MIM) with zinc nitrate hexahydrate in methanol at 40 oC for 2 h.39 The ZIF8 nanoparticles exhibit polyhedron-like morphology with TEM diameters of approximately 60, 110 and 200 nm, respectively (Figure 1a i-iii). The hydrodynamic sizes of the nanoparticles from


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dynamic light scattering are a little bigger than those observed under TEM (Figure S1 and Table S1, Supporting Information), which is because of the hydration of the nanoparticles. The X-ray diffraction (XRD) pattern of the ZIF-8 nanoparticles (Figure S2, Supporting Information) is identical with the previous work,40 which proves that the ZIF-8 nanomaterials have been successfully prepared. The thermogravimetric analysis (TGA) results show that ZIF-8 nanoparticles have a superior thermal stability and the beginning of weight loss is at 500 oC (Figure S3, Supporting Information), which provide a minimum pyrolysis temperature for preparation of ZCNs. Nitrogen adsorption-desorption isotherms experiments testify the pore characteristics of ZIF-8 (110 nm), with a specific surface area of 1394 m3 g-1, a cumulative pore volume of 1.2 cm3 g-1, and pore size of 3.5 nm (Figure S4, Supporting Information).

Figure 1. Characterization of ZCNs. (a) TEM images of ZIF-8 nanoparticles: (i) 60, (ii) 110, and (iii) 200 nm, and ZIF-8 derived carbon nanoparticles: (iv) ZCN-60, (v) ZCN-110, and (vi) ZCN-


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200. The scale bars are 100 nm. Raman spectrum (b), high-resolution N1s XPS spectrum (c) and power XRD pattern (d) of ZCN-110.

Subsequently, ZCNs are fabricated via thermal-annealing (900 oC) of ZIF-8 nanoparticles under a N2 atmosphere. Figure 1a iv-vi are the TEM images of ZCNs, which show that there are little influence on the morphology of ZCNs compared with ZIF-8 precursor nanoparticles. In the Raman spectrum of ZCNs (Figure 1b and Figure S5, Supporting Information), the D band (1341 cm-1) corresponds to disordered carbon or defective graphitic structures and the G band (1582 cm-1) is a typical feature of graphitic28. The ID / IG ratio of ≈1.08 reveals large amounts of heteroatom doped graphitic defects are generated. The heteroatom doping is also confirmed by X-ray photoelectron spectroscopy (XPS) spectra (Figure S6, Supporting Information), which confirms the presence of C, N, O and Zn element. Meanwhile, the high-resolution N1s XPS spectrum of ZCNs (Figure 1c and Figure S7, Supporting Information) can be deconvoluted into three peaks:28 pyridinic N (398.4 eV), pyrrolic N (400.3 eV) and quaternary N (402.8 eV). The XRD pattern of ZCNs is shown in Figure 1d (and Figure S8, Supporting Information), and the nanoparticles reveal a similar broad peak at ≈ 26o, which is consistent with the carbon peak (002) that is a characteristic of graphitic carbon materials41 and without signals of Zn and ZnO. Nitrogen adsorption-desorption isotherms experiments prove the pore characteristics of the ZCN110 (the size of the ZIF-8 precusor nanoparticles is 110 nm), with a specific surface area of 850.2 m3 g-1, a cumulative pore volume of 0.645 cm3 g-1, and pore size of 3.0 nm (Figure S9, Supporting Information). Compared with the ZIF-8 nanoparticles, the ZCNs retain much of the internal porosity, this phenomenon also proves that directly pyrolysis of ZIF-8 to prepare ZCNs is simple and effective method. Finally, to obtain a good physiological stability, mPEG-DSPE (5


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kD) is utilized to modify ZCNs. The ζ-potential of PEGylated ZCN-110 changes from -19.6 mV to -3.6 mV (Figure S10 and Table S2, Supporting Information), which proves that successful modification of mPEG-DSPE, and DLS data illustrate the hydrodynamic size of PEGylated ZCNs (Figure S11 and Table S1, S2 and S3, Supporting Information). Compared to the previous work,30 which employ SiO2 as template to avoid aggregation of carbon nanoparticles, our method via directly thermal-annealing is simple and convenient. 3.2 Photothermal effects of ZCNs The application of nanomaterials with a high NIR absorption and photothermal conversion efficiency for PTT is highly desirable since these can produce a larger temperature variation upon NIR irradiation.37,

42

Notable, due to the constitution of graphite-like carbon from the

ZCNs, these nanomaterials are generally regarded as good photothermal agents for PTT. The results show that original ZIF-8 nanoparticles have rarely photothermal effects (Figure 2a). However, after the carbonization, all the ZCNs have a potential as photothermal agents. Meanwhile, with the increase of carbonized temperature, the photothermal effects improve and ZCN-110 (900 oC) shows the best photothermal effects with the temperature elevated ≈ 40 oC, further increase in temperature reduces the photothermal effect of ZCN-110 (1000 oC). To reveal the rule of the photothermal effects, UV-Vis spectra are measured (Figure S12, Supporting Information), the UV-Vis absorption at 808 nm enhanced with the increase of carbonized temperature. The relationship between photothermal effects and absorbance at 808 nm are shown in Figure 2b, the results indicate that the improvement of photothermal effects can be contribute to the increase of absorbance at 808 nm. Hence, 900 oC is an ideal carbonization temperature for photothermal effects and selected for the following research.


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Figure 2. Photothermal effects of ZCNs. (a) Photothermal effects of ZCN-110 with different pyrolysis temperatures under NIR laser irradiation (50 μg mL-1, 808 nm, 3 W cm-2). (b) A relationship between the maximum temperature change with different nanoparticles suspensions, together with the relevant UV absorbance at 808 nm. (c) The photothermal effects of ZCN-60, ZCN-110, and ZCN-200 dispersion (50 μg mL−1, 808 nm, 3 W cm−2). (d) UV-Vis absorbance spectra of ZCN-60, ZCN-110 and ZCN-200 aqueous dispersions (50 μg mL−1).

Meanwhile, according to our knowledge, many nanoparticles own an enhanced photothermal effects with the increase of nanoparticle size.33-35 Hence, three sizes of ZCNs (60, 110 and 200 nm) are utilized to demonstrate whether the size of nanoparticles do influence on the photothermal performance. The results show an enhanced photothermal effects with the increase of size of ZCNs (Figure 2c). The ZCN-200 can elevate the temperature to 70 oC after NIR laser


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irradiation (808 nm, 3 W cm-2), however, the temperatures raise to 64.5 oC and 60 oC for ZCN110 and ZCN-60. To find the reason for this phenomenon, two factors are considered: the absorbance at 808 nm and photothermal conversion efficiency (η). As shown in the Figure 2d, the absorbance of ZCNs show an increase behavior with the increase of nanoparticles size at 808 nm. Meanwhile, the η values of ZCN-60, ZCN-110 and ZCN-200 are calculated as 36.5%, 42.7% and 41.6%, respectively (Figure S13, Supporting Information). The photothermal conversion efficiency of ZCN-200 and ZCN-110 are higher than other kind of photothermal agents, such as carbon nanospheres,30 carbon dots43 and gold nanoshells44. Therefore, owing to the enhanced NIR absorbance and photothermal conversion efficiency, the ZCNs own an enhanced photothermal effects with the increase of size. 3.3 ROS generation of ZCNs With a porphyrin-like structure of carbon nanoparticles, which has been proved that porphyrin -like structure45-46 is constructed from a divacancy and a four pyridinic N’s, and strong NIR absorbance, these materials also have the prerequisites as PDT photosensitizer.30 To confirm the ROS generation of ZCNs upon NIR laser irradiation, free indocyanine green (ICG) is selected as the reference to calculate the ROS quantum yield of different sizes of ZCNs. In the experiment, the absorptions at 808 nm of ZCNs and ICG-phosphate-buffered saline (PBS) solution are adjusted to about 0.5 OD to avoid inner-filter effects. As shown in Figure 3a-d, the UV-Vis absorbance at 419 nm of both ICG and ZCNs systems have a decline after NIR laser irradiation, which is the characteristic absorption of 1,3-diphenylisobenzofuran (DPBF) as the ROS trapping agent,47 indicating that DPBF is photo-bleached by ROS generated by ZCNs and ICG. The rate constant for DPBF decomposition by ZCNs is little faster than that of ICG (Figure S14, Supporting Information). Moreover, compared with ICG (ΦICG=0.0020), the ROS quantum


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yields of ZCN-60, ZCN-110 and ZCN-200 are calculated to be ≈ 0.0022, 0.0023 and 0.0024, respectively. The results also show the generation of ROS enhanced with the increase of nanoparticle size. Meanwhile, we find out that Zn element is not the key factor for ZCNs to generate ROS. After HCl solution treatment, ZCN-110 (non-Zn) is utilized to confirm the ROS generation upon NIR laser irradiation. As the results shown (Figure S15, Supporting Information), DPBF is also photo-bleached by ZCN-110 (non-Zn) and the ROS quantum yield is ≈ 0.0019, which is slightly lower than the value of ZCN-110. The results prove that non-Zn ZCN-110 can also generate ROS and Zn element in the ZCNs only slightly affect the efficiency of generation of ROS. To visually observe the generation of ROS, we also investigate the intracellular ROS generation via the fluorescent probe, dichlorofluorescein diacetate (DCFH-DA).48 As a representative, ZCN-110 is selected to incubate with A549 cells (a human alveolar basal epithelial cell line) for confocal laser scanning microscopy (CLSM) experiments. In Figure 3e, the control group and ZCN-110 group both show relatively shallow fluorescence signal which suggest less ROS is produced, however, the experiment group (ZCN-110 + NIR) emits much brighter fluorescence than that shown in other groups, suggesting ZCNs can produce ROS in live cells with NIR laser irradiation.


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Figure 3. Photo-degradation of DPBF by ICG (a), ZCN-60 (b), ZCN-110 (c) and ZCN-200 (d) under NIR laser irradiation (808 nm, 3 W cm−2, 5 min). (e) CLSM images to visualize the intracellular ROS generation in ZCN-110 group (12.5 μg mL−1) and ZCN-110+NIR group, respectively. The scale bars are 50 μm in the images.

3.4 In vitro phototherapy Encouraged by the excellent phototherapy results, we further investigate its bioapplication in vitro. Standard MTT assay is employed to reveal the phototherapy efficacy of ZCNs in vitro. First, the biocompatibility of ZCNs (60, 110 and 200 nm) are measured with 293T cell lines (Figure 4a), indicating the ZCNs have a good biocompatibility with normal cells, meanwhile, the dark toxicity of ZCNs are measured with A549 cell lines for 24 h. As shown in Figure 4b, all A549 cell viabilities are over 90%, even at the highest concentration (200 μg mL-1), indicating the excellent biocompatibility of ZCNs. Subsequently, in order to test the phototherapy effect in vitro, cellular uptake experiments are taken to verify the suitable treatment point, the results (Figure S16, Supporting Information) show that 4 h is enough for ZCNs to uptake, then the ZCNs are cultured with A549 cancer cells and irradiated with the 808 nm laser (3 W cm-2, 5 min). As shown in Figure 4c, A549 cells are killed in a dosage-dependent behavior after 808 nm laser treated with ZCNs, and the IC50 of ZCN-60, ZCN-110 and ZCN-200 for phototherapy are 37.6, 36.1 and 33.7 μg mL-1, respectively. Noteworthy, when the concentration of ZCNs is 50 μg mL-1, the MTT results reveal that ZCN-110 and ZCN-200 hold a significant better phototherapy effects to kill cancer cells compared with ZCN-60 group, meanwhile, a much significant results appear when the concentration rises up to 100 μg mL-1. This phenomenon can attribute to the enhanced phototherapy effects with the increase of nanoparticle size, which is because of the


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photothermal effects and ROS generation enhanced with the increase of nanoparticle size, respectively, and the combination of PTT and PDT can kill much more cancer cells. Meanwhile, as a representative, the respective PDT and PTT therapeutic effects of ZCN-110 are further measured (Figure 4d). For the 4 oC+NIR group, which eliminate the heating effect of photothermal effects, and the results predominate to a PDT effect. The cell viability is about 45% when the concentration is 50 μg mL-1. Meanwhile, NaN3, which is a well-known ROS scavenger to avoid ROS generation and the 25 oC+NIR+NaN3 group reveal the PTT effect, and the cell viability is about 38%. However, the cell viability of 25 oC+NIR group is about 18% when the concentration is 50 μg mL-1, this result illustrates that the generated heat and ROS by the ZCNs can effective kill cancer cells by the combination of PTT and PDT. Meanwhile, confocal fluorescence imaging of calcein acetoxymethyl ester (calcein-AM) and propodium (PI) costained with A549 cells also reveal the phototherapy efficacy of ZCN-110. From the CLSM pictures (Figure 4e), the results show that the cells are barely alive, which illustrates the ZCNs could kill cancer cells under NIR laser irradiation. Hemolysis experiments are measured to detect the biocompatibility of ZCNs (Figure S17, Supporting Information), the distilled water group shown obvious color change, however, the PBS group and of ZCNs group (200 μg mL-1) show clear supernatant, indicating a good biocompatibility and biosafety for injection.


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Figure 4. Cell viability of 293T cells (a) and A549 cells (b) incubated with ZCN-60, ZCN-110 and ZCN-200 for 24 h with different concentrations. (c) In vitro phototherapy efficacy of ZCN60, ZCN-110 and ZCN-200 of various concentrations on A549 cells upon NIR laser irradiation (808 nm, 3 W cm-2, irradiation time = 300 s). (d) Cell viability of A549 cells following PDT group (4 oC+NIR), PTT group (25 oC+NIR+NaN3), and simultaneous PDT/PTT group (25 oC+NIR)

of ZCN-110. (e) CLSM images of Calcein AM (green, live cells) and PI (Propidium

iodide) (red, dead cells) co-stained A549 cells treated by blank group and ZCN-110 group with NIR laser irradiation (50 μg mL-1, 808 nm, 3 W cm-2) for 300 s. White bars stand for 50 μm in the images. 3.5 Photoacoustic imaging Because of the strong NIR absorption, carbon nanomaterials have been extensively utilized in photoacoustic imaging (PAI) technique,32, 38 which provides not only good spatial resolution but also high imaging depth compared to conventional optical imaging technique. The PA imaging capacity of ZCNs are evaluated, as shown in Figure 5a, the PA signal intensity of ZCNs reach


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the highest at the excitation wavelength of 718 nm, which could reduce the interference of hemoglobin (760 nm) and oxygenated homolobin (850 nm).49 Meanwhile, the PA signal enhanced with the increase of the concentration of ZCNs (Figure 5b), demonstrating that ZCNs can be a good contrast agent for PA imaging. Interestingly, the PA signal intensity at 718 nm also enhanced with the increase of the nanoparticle size. This behavior is attributed to the enhanced photothermal effects with the increase size of ZCNs, meanwhile thermal effect generates different thermal expansion and leading to enhanced PA signal with the increase of nanoparticle size.50 Subsequently, Mice bearing A549 tumors nude mice are selected to investigate the accumulation of nanoparticles in vivo. ZCNs dispersion (2 mg mL-1, 100 μL) are administered to mice by tail vein injection, meanwhile, the PA signals at tumor region are measured at different time points (0, 2, 4, 6, 8 and 24 h). Subsequently, in order to eliminate the interference from hemoglobin and oxygerated homolobin, the obtained PA signals are processed with the unmixing spectra module. As shown in Figure 5c (and Figure S18, Supporting Information) the PA signals of tumor region reach maximum at 4 h for ZCN-60 and ZCN-110, and at 6 h for ZCN-200, indicating highest nanoparticles accumulation in tumor is around 4 h or 6 h post injection. Meanwhile, the quantification value of PA signal of ZCNs at tumor region are obtained (Figure S19, Supporting Information). For example to ZCN-110 group, before injection and 4 h post injection, the PA intensity of tumor region is calculated as 0.019 ± 0.03 and 0.98 ± 0.03, which indicating a good accumulation in tumor site at 4 h. In brief, the PA imaging in vivo fully prove that ZCNs are suitable as PA imaging agents, meanwhile, 4 or 6 h after intravenous injection is the best time point for tumor phototherapy time for ZCN-60, ZCN-110 and ZCN-200, respectively.


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Figure 5. In vitro/vivo PA imaging of ZCNs. (a) PA signal intensity of ZCNs in vitro at various excitation wavelength. (b) Linear relation between PA signal in vitro versus various concentration of ZCNs nanoparticles. (c) PA imaging profiles (top row: ZCN-60; middle row: ZCN-110; bottom row: ZCN-200) of tumor region at different intravenous injection time in A549 tumor-bearing mice. (d) Infrared thermal images of mice treated with PBS, ZCN-60, ZCN-


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110 and ZCN-200 (100 μL, 3 mg mL−1) under NIR laser irradiation (808 nm, 3 W cm−2) for 300 s. To further verify the PA imaging results of ZCNs in vivo, then we study the biodistribution and pharmacokinetics by measuring the fluorescent signal of ZCNs in different organs and the blood. The biodistribution experiments (Figure S20, Supporting Information) verify the ZCN-60, ZCN-110 and ZCN-200 are accumulated in tumors by the enhanced penetration and retention effect of NPs, the accumulation amounts of ZCNs in tumors are calculated as 6.78 ± 2.07, 7.65 ± 2.16 and 8.61 ± 2.05% ID/g, respectively. Then with time prolong to 24 h, the nanoparticles are metabolized from the mice. Meanwhile, the blood levels of ZCNs reduced gradually with time prolongs, and the half-lives for those nanoparticles in vivo are determined to be 4.12 ± 1.36 h, 4.02 ± 1.28 h and 3.89 ± 1.08 h for ZCN-60, ZCN-110 and ZCN-200, respectively (Figure S21, Supporting Information). 3.6 In vivo phototherapy Being aware of the excellent phototherapy effect of ZCNs in vitro, the antitumor phototherapy efficacy in vivo are firstly pre-evaluated with A549 tumor-bearing mice. After an intravenous injection of 100 μL of nanomaterials suspension (3 mg mL-1), laser irradiation are performed with an 808 nm laser (3 W cm-2) for 5 min at 4 h for ZCN-60 and ZCN-100 and 6 h for ZCN-200 post-injection, respectively. IR thermal camera is used to monitor the photothermal performance in vivo. As shown in Figure 5d, after 5 min laser irradiation, the tumor temperature of mice for ZCN-200 group rapidly increased from 31.1 oC to 55.1 oC (ΔT=24 oC), while the ZCN-110 and ZCN-60 can only raise up to 48.2 oC and 42.8 oC respectively. These results reveal that ZCN-200 have a better photothermal performance in vivo than ZCN-110 and ZCN-60, which is likely attributed to the size-dependent photothermal behavior of ZCNs. In contrast, the tumor


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temperature of mice with PBS treatment only increase 9.1 oC, indicating that NIR laser at such power intensity could not induce sufficient heating effect. Meanwhile, considering the minimum damage to the skin, different conditions are used to test the phototherapy in vitro (Figure S22 and Figure S23, Supporting Information), finally, we find out that 1 W cm-2, 10 min is also an suitable condition for phototherapy (Figure S24, Supporting Information). Based on the above results and analysis, we perform the oncotherapy experiments in vivo. A549 tumor-bearing BALB/c nude mice with tumor volume of ≈ 80 mm3 are randomly divided into four groups (6 mice per group), then the nanoparticles dispersion are injected through tail vein. As shown in Figure 6b and 6c, the tumor in PBS+NIR group grow rapidly, while the tumors in ZCN-110 (3 W cm-2, 5 min) group are re-growing, and the antitumor rate calculated from tumor weight are 50%, revealing inefficient tumor ablation effect of ZCN-110, which probably own to their relatively lower phototherapy effects. However, the tumors in ZCN-200 (3 W cm-2, 5 min) group are completely eliminated within 14 days with no recrudescence. These results are in accordance with the IR thermal imaging experiments shown in Figure 5d. To confirm the biocompatibility of ZCNs, the body weights of mice are supervised, and the weights in each groups keep growing, indicating the ZCNs don’t induce systemic toxicity. And after 14th day therapy, all mice are euthanized and the major organ are excised for hematoxylin and eosin (H&E) test. As shown in Figure 6d, there are no obvious organ damage and inflammatory compared to PBS+NIR group. Meanwhile, biosafety in vivo is also evaluated by the blood chemistry and the results (Figure S25, supporting Information) show negligible differences between ZCNs group and control group, indicating the good biosafety of ZCNs in vivo. Furthermore, high antitumor capability (97 %) are also observed on ZCN-200 (1 W cm-2, 10 min) treated mice (Figure 6a-d and Figure S24, Supporting Information), suggesting that


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excellent phototherapy effect of ZCNs could be realized even at a lower power density. Hence, there data indicate that ZCNs are promising phototherapy agent in oncotherapy and with relatively low systemic toxicity.


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Figure 6. In vivo phototherapy. (a) Body weight curves after different treatments during a period of time. (b) Growth curves of A549 tumors on mice of different groups after corresponding treatments as indicated. (c) Photographs of tumors dissected for each groups at the 14th day after phototherapy treatment and comparison of tumor weight of each groups. (d) H&E staining images of major organs dissected from each experiment group. (40×). **, p < 0.01; ***, p < 0.001.

4. CONCLUSIONS In summary, we investigate the pyrolysis temperature and size of ZIF-8 derived carbon nanoparticles as theranostic agents for PA imaging-guided phototherapy. Meanwhile, when the pyrolysis temperature is 900 oC, the ZCNs show the best photothermal effects. Moreover, we find out an enhanced phototherapy effect and PA imaging capability of ZCNs is accompanied with the increasement of size, which have been proved in vitro anticancer experiments. In vitro and in vivo experiments confirm the PA imaging guided ZCNs can completely inhibit tumor growth with minimal side effect, even if the NIR laser power is 1 W cm-2, the anti-tumor effectively is also 97%. Our research proves that the ZIF-8 derived carbon nanoparticles are expected to have wide applications in the phototherapy of cancer, and the concept of sizedependent enhanced behavior of phototherapy and PA imaging capability can be very useful in the design and development of novel materials with higher performances for cancer therapy.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.


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Characterization, live/dead cell viability assay, ROS measurements of ZCNs in vitro, calculation of the photothermal conversion efficiency and singlet oxygen quantum-yield. Further information relating to the DLS, XRD, TGA and BET data about ZIF-8 nanoparticles and DLS, Zeta potential, Raman, XPS, high-resolution N1s XPS, XRD, BET and UV data about ZCNs, PAI images of ZCNs, quantitative analysis of PAI signal and infrared thermal images. AUTHOR INFORMATION Corresponding Author *Telephone: +86-21-31242385. Fax: +86-21-31248888. Email: [email protected]

ORCID Wuli Yang: 0000-0003-0384-9213

Notes The authors declare no competing financial interest.

Acknowledgments This work was supported by the National Key R&D Program of China (Grant No. 2016YFC1100300) and National Science Foundation of China (Grant Nos. 51473037 and 51873041).


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References (1) Ferrari, M. Cancer Nanotechnology: Opportunities and Challenges. Nat. Rev. Cancer 2005, 5, 161-171. (2) Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin. 2017, 67, 7-30. (3) Wang, S.; Huang, P.; Nie, L.; Xing, R.; Liu, D.; Wang, Z.; Lin, J.; Chen, S.; Niu, G.; Lu, G.; Chen, X. Single Continuous Wave Laser Induced Photodynamic/Plasmonic Photothermal Therapy Using Photosensitizer-Functionalized Gold Nanostars. Adv. Mater. 2013, 25, 30553061. (4) Lin, J.; Wang, S.; Huang, P.; Wang, Z.; Chen, S.; Niu, G.; Li, W.; He, J.; Cui, D.; Lu, G.; Chen, X.; Nie, Z. Photosensitizer-Loaded Gold Vesicles with Strong Plasmonic Coupling Effect for Imaging-Guided Photothermal/Photodynamic Therapy. ACS Nano 2013, 7, 5320-5329. (5) Cheng, L.; Wang, C.; Feng, L.; Yang, K.; Liu, Z. Functional Nanomaterials for Phototherapies of Cancer. Chem. Rev. 2014, 114, 10869-10939. (6) Xie, L.; Wang, G.; Zhou, H.; Zhang, F.; Guo, Z.; Liu, C.; Zhang, X.; Zhu, L. Functional Long Circulating Single Walled Carbon Nanotubes for Fluorescent/Photoacoustic ImagingGuided Enhanced Phototherapy. Biomaterials 2016, 103, 219-228. (7) Yang, Y.; Zhu, W.; Dong, Z.; Chao, Y.; Xu, L.; Chen, M.; Liu, Z. 1D Coordination Polymer Nanofibers for Low-Temperature Photothermal Therapy. Adv. Mater. 2017, 29,1703588. (8) Park, J.; Jiang, Q.; Feng, D.; Mao, L.; Zhou, H. C. Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy. J. Am. Chem. Soc. 2016, 138, 3518-3525.


25


(9) Kuo, W. S.; Chang, C. N.; Chang, Y. T.; Yang, M. H.; Chien, Y. H.; Chen, S. J.; Yeh, C. S. Gold Nanorods in Photodynamic Therapy, as Hyperthermia Agents, and in Near-Infrared Optical Imaging. Angew. Chem. Int. Ed. 2010, 49, 2711-2715. (10) Jang, B.; Park, J. Y.; Tung, C. H.; Kim, I. H.; Choi, Y. Gold Nanorod-Photosensitizer Complex for Near-Infrared Fluorescence Imaging and Photodynamic/Photothermal Therapy in Vivo. ACS Nano 2011, 5, 1086-1094. (11) Vankayala, R.; Lin, C. C.; Kalluru, P.; Chiang, C. S.; Hwang, K. C. Gold NanoshellsMediated Bimodal Photodynamic and Photothermal Cancer Treatment Using Ultra-Low Doses of Near Infra-Red Light. Biomaterials 2014, 35, 5527-5538. (12) Robinson, J. T.; Tabakman, S. M.; Liang, Y.; Wang, H.; Casalongue, H. S.; Vinh, D.; Dai, H. Ultrasmall Reduced Graphene Oxide with High Near-Infrared Absorbance for Photothermal Therapy. J. Am. Chem. Soc. 2011, 133, 6825-6831. (13) Sahu, A.; Choi, W. I.; Lee, J. H.; Tae, G. Graphene Oxide Mediated Delivery of Methylene Blue for Combined Photodynamic and Photothermal Therapy. Biomaterials 2013, 34, 6239-6248. (14) Hong, G.; Diao, S.; Antaris, A. L.; Dai, H. Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy. Chem. Rev. 2015, 115, 10816-10906. (15) Yong, Y.; Zhou, L.; Gu, Z.; Yan, L.; Tian, G.; Zheng, X.; Liu, X.; Zhang, X.; Shi, J.; Cong, W.; Yin, W.; Zhao, Y. WS2 Nanosheet as A New Photosensitizer Carrier for Combined Photodynamic and Photothermal Therapy of Cancer Cells. Nanoscale 2014, 6, 10394-10403. (16) Liu, T.; Wang, C.; Cui, W.; Gong, H.; Liang, C.; Shi, X.; Li, Z.; Sun, B.; Liu, Z. Combined Photothermal and Photodynamic Therapy Delivered by PEGylated MoS2 Nanosheets. Nanoscale 2015, 7, 9945.


26

Page 26 of 32

Page 27 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(17) Rosi, N. L.; Eckert, J.; Eddaoudi, M.; Vodak, D. T.; Kim, J.; O'Keeffe, M.; Yaghi, O. M. Hydrogen Storage in Microporous Metal-Organic Frameworks. Science 2003, 300, 1127-1129. (18) Farha, O. K.; Özgür Yazaydın, A.; Eryazici, I.; Malliakas, C. D.; Hauser, B. G.; Kanatzidis, M. G.; Nguyen, S. T.; Snurr, R. Q.; Hupp, J. T. De Novo Synthesis of a Metal– Organic Framework Material Featuring Ultrahigh Surface Area and Gas Storage Capacities. Nat. Chem. 2010, 2, 944. (19) Inukai, M.; Tamura, M.; Horike, S.; Higuchi, M.; Kitagawa, S.; Nakamura, K. Storage of CO2 Into Porous Coordination Polymer Controlled by Molecular Rotor Dynamics. Angew. Chem. Int. Ed. 2018, 57, 8687-8690. (20) Zhao, M.; Yuan, K.; Wang, Y.; Li, G.; Guo, J.; Gu, L.; Hu, W.; Zhao, H.; Tang, Z. MetalOrganic Frameworks as Selectivity Regulators for Hydrogenation Reactions. Nature 2016, 539, 76-80. (21) Huang, N.; Drake, H.; Li, J.; Pang, J.; Wang, Y.; Yuan, S.; Wang, Q.; Cai, P.; Qin, J.; Zhou, H.-C. Flexible and Hierarchical Metal-Organic Framework Composites for HighPerformance Catalysis. Angew. Chem. Int. Ed. 2018, 57, 8916-8920. (22) Tao, W.; Zhu, X.; Yu, X.; Zeng, X.; Xiao, Q.; Zhang, X.; Ji, X.; Wang, X.; Shi, J.; Zhang, H.; Mei, L. Black Phosphorus Nanosheets as a Robust Delivery Platform for Cancer Theranostics. Adv. Mater. 2017, 29, 1603276. (23) Horcajada, P.; Chalati, T.; Serre, C.; Gillet, B.; Sebrie, C.; Baati, T.; Eubank, J. F.; Heurtaux, D.; Clayette, P.; Kreuz, C.; Chang, J. S.; Hwang, Y. K.; Marsaud, V.; Bories, P. N.; Cynober, L.; Gil, S.; Ferey, G.; Couvreur, P.; Gref, R. Porous Metal-Organic-Framework Nanoscale Carriers as a Potential Platform for Drug Delivery and Imaging. Nat. Mater. 2010, 9, 172-178.


27


(24) Horcajada, P.; Gref, R.; Baati, T.; Allan, P. K.; Maurin, G.; Couvreur, P.; Ferey, G.; Morris, R. E.; Serre, C. Metal-Organic Frameworks in Biomedicine. Chem. Rev. 2012, 112, 1232-1268. (25) Zhang, Y.; Wang, F. M.; Ju, E. G.; Liu, Z.; Chen, Z. W.; Ren, J. S.; Qu, X. G. MetalOrganic-Framework-Based Vaccine Platforms for Enhanced Systemic Immune and Memory Response. Adv. Funct. Mater. 2016, 26, 6454-6461. (26) Liu, B.; Shioyama, H.; Akita, T.; Xu, Q. Metal-Organic Framework as a Template for Porous Carbon Synthesis. J. Am. Chem. Soc. 2008, 130, 5390-5391. (27) Torad, N. L.; Hu, M.; Kamachi, Y.; Takai, K.; Imura, M.; Naito, M.; Yamauchi, Y. Facile Synthesis of Nanoporous Carbons with Controlled Particle Sizes by Direct Carbonization of Monodispersed ZIF-8 crystals. Chem. Commun. 2013, 49, 2521-2523. (28) Zheng, F.; Yang, Y.; Chen, Q. High Lithium Anodic Performance of Highly NitrogenDoped Porous Carbon Prepared from a Metal-Organic Framework. Nat. Commun. 2014, 5, 5261. (29) Yang, H.; Bradley, S. J.; Chan, A.; Waterhouse, G. I. N.; Nann, T.; Kruger, P. E.; Telfer, S. G. Catalytically Active Bimetallic Nanoparticles Supported on Porous Carbon Capsules Derived From Metal–Organic Framework Composites. J. Am. Chem. Soc. 2016, 138, 1187211881. (30) Wang, S.; Shang, L.; Li, L.; Yu, Y.; Chi, C.; Wang, K.; Zhang, J.; Shi, R.; Shen, H.; Waterhouse, G. I.; Liu, S.; Tian, J.; Zhang, T.; Liu, H. Metal-Organic-Framework-Derived Mesoporous Carbon Nanospheres Containing Porphyrin-Like Metal Centers for Conformal Phototherapy. Adv. Mater. 2016, 28, 8379-8387. (31) Yang, K.; Zhang, S.; Zhang, G.; Sun, X.; Lee, S. T.; Liu, Z. Graphene in Mice: Ultrahigh in Vivo Tumor Uptake and Efficient Photothermal Therapy. Nano Lett. 2010, 10, 3318-3323.


28

Page 28 of 32

Page 29 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(32) Chen, D. Q.; Wang, C.; Nie, X.; Li, S. M.; Li, R. M.; Guan, M. R.; Liu, Z.; Chen, C. Y.; Wang, C. R.; Shu, C. Y.; Wan, L. J. Photoacoustic Imaging Guided Near-Infrared Photothermal Therapy Using Highly Water-Dispersible Single-Walled Carbon Nanohorns as Theranostic Agents. Adv. Funct. Mater. 2014, 24, 6621-6628. (33) Shen, S.; Wang, S.; Zheng, R.; Zhu, X.; Jiang, X.; Fu, D.; Yang, W. Magnetic Nanoparticle Clusters for Photothermal Therapy with Near-Infrared Irradiation. Biomaterials 2015, 39, 67-74. (34) Peng, H. B.; Tang, S. W.; Tian, Y.; Zheng, R.; Zhou, L.; Yang, W. L. Highly LigandDirected and Size-Dependent Photothermal Properties of Magnetite Particles. Part. Part. Syst. Charact. 2016, 33, 332-340. (35) Peng, H.; Tang, J.; Zheng, R.; Guo, G.; Dong, A.; Wang, Y.; Yang, W. Nuclear-Targeted Multifunctional Magnetic Nanoparticles for Photothermal Therapy. Adv. Healthcare Mater. 2017, 6, 1601289. (36) Zhang, Z.; Wang, J.; Nie, X.; Wen, T.; Ji, Y.; Wu, X.; Zhao, Y.; Chen, C. Near Infrared Laser-Induced Targeted Cancer Therapy Using Thermoresponsive Polymer Encapsulated Gold Nanorods. J. Am. Chem. Soc. 2014, 136, 7317-7326. (37) Tian, Y.; Zhang, J.; Tang, S.; Zhou, L.; Yang, W. Polypyrrole Composite Nanoparticles with Morphology-Dependent Photothermal Effect and Immunological Responses. Small 2016, 12, 721-726. (38) Ge, J.; Jia, Q.; Liu, W.; Guo, L.; Liu, Q.; Lan, M.; Zhang, H.; Meng, X.; Wang, P. RedEmissive Carbon Dots for Fluorescent, Photoacoustic, and Thermal Theranostics in Living Mice. Adv. Mater. 2015, 27, 4169-4177.


29


(39) Venna, S. R.; Jasinski, J. B.; Carreon, M. A. Structural Evolution of Zeolitic Imidazolate Framework-8. J. Am. Chem. Soc. 2010, 132, 18030-18033. (40) Park, K. S.; Ni, Z.; Cote, A. P.; Choi, J. Y.; Huang, R.; Uribe-Romo, F. J.; Chae, H. K.; O'Keeffe, M.; Yaghi, O. M. Exceptional Chemical and Thermal Stability of Zeolitic Imidazolate Frameworks. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 10186-10191. (41) Zhang, L.; Su, Z.; Jiang, F.; Yang, L.; Qian, J.; Zhou, Y.; Li, W.; Hong, M. Highly Graphitized Nitrogen-Doped Porous Carbon Nanopolyhedra Derived from ZIF-8 Nanocrystals as Efficient Electrocatalysts for Oxygen Reduction Reactions. Nanoscale 2014, 6, 6590-6602. (42) de Melo-Diogo, D.; Pais-Silva, C.; Dias, D. R.; Moreira, A. F.; Correia, I. J. Strategies to Improve Cancer Photothermal Therapy Mediated by Nanomaterials. Adv. Healthcare Mater. 2017, 6, 1700073. (43) Geng, B.; Yang, D.; Pan, D.; Wang, L.; Zheng, F.; Shen, W.; Zhang, C.; Li, X. NIRResponsive Carbon Dots for Efficient Photothermal Cancer Therapy at Low Power Densities. Carbon 2018, 134, 153-162. (44) Hessel, C. M.; Pattani, V. P.; Rasch, M.; Panthani, M. G.; Koo, B.; Tunnell, J. W.; Korgel, B. A. Copper Selenide Nanocrystals for Photothermal Therapy. Nano Lett. 2011, 11, 2560-2566. (45) Lee, D. H.; Lee, W. J.; Lee, W. J.; Kim, S. O.; Kim, Y. H. Theory, Synthesis, and Oxygen Reduction Catalysis of Fe-Porphyrin-Like Carbon Nanotube. Phys. Rev. Lett. 2011, 106, 175502. (46) Zhu, Y.; Zhang, B.; Liu, X.; Wang, D. W.; Su, D. S. Unravelling the Structure of Electrocatalytically Active Fe-N Complexes in Carbon for the Oxygen Reduction Reaction. Angew. Chem. Int. Ed. 2014, 53, 10673-10677.


30

Page 30 of 32

Page 31 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(47) Wang, L.; Sun, Q.; Wang, X.; Wen, T.; Yin, J. J.; Wang, P.; Bai, R.; Zhang, X. Q.; Zhang, L. H.; Lu, A. H.; Chen, C. Using Hollow Carbon Nanospheres as a Light-Induced Free Radical Generator to Overcome Chemotherapy Resistance. J. Am. Chem. Soc. 2015, 137, 1947-1955. (48) Lucky, S. S.; Muhammad Idris, N.; Li, Z.; Huang, K.; Soo, K. C.; Zhang, Y. Titania Coated Upconversion Nanoparticles for Near-Infrared Light Triggered Photodynamic Therapy. ACS Nano 2015, 9, 191-205. (49) Vogel, A.; Venugopalan, V. Mechanisms of Pulsed Laser Ablation of Biological Tissues. Chem. Rev. 2003, 103, 577-644. (50) Pu, K.; Shuhendler, A. J.; Jokerst, J. V.; Mei, J.; Gambhir, S. S.; Bao, Z.; Rao, J. Semiconducting Polymer Nanoparticles as Photoacoustic Molecular Imaging Probes in Living Mice. Nat. Nanotechnol. 2014, 9, 233-239.


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