Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by

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Functional Inorganic Materials and Devices

Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by Ultrathin MnO2 Nanosheet Li Wang, Shanyue Guan, Yangziwan Weng, Simin Xu, Heng Lu, Xiang-Min Meng, and shuyun zhou ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b20639 • Publication Date (Web): 23 Jan 2019 Downloaded from http://pubs.acs.org on January 25, 2019

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ACS Applied Materials & Interfaces

Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by Ultrathin MnO2 Nanosheet Li Wang,a,b Shanyue Guan,*a Yangziwan Weng,a,b Si-Min Xu,c Heng Lu,a Xiangmin Menga and Shuyun Zhou*a

aKey

Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of

Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. bUniversity cState

of Chinese Academy of Sciences, Beijing 100190, P. R. China.

Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology,

Beijing 100029, P. R. China.

ABSTRACT: In the medical applications, two-dimensional nanomaterials have been widely studied, on account of its intriguing properties such as good biocompatibility, stability and multifunctionality. Herein, an ultrathin MnO2 nanosheet has been fabricated by a simplistic hydrothermal process. The high photothermal conversion performance (62.4%) can be attributed to the vacancy in ultrathin MnO2 nanosheet, as confirmed by the extended X-ray absorption fine structure (EXAFS) results and the density functional theory (DFT) calculation, benefiting photoacoustic imaging-guided cancer therapy. This high efficient vacancy-induced photothermal therapy has been reported for the first time. As a result, this work demonstrates that this ultrathin MnO2 nanosheet has potential to construct a nanosystem for imagingguided cancer therapy.

KEYWORDS: ultrathin, MnO2, vacancy, PTT.

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INTRODUCTION Cancer has continuously threatened the public health over the decades. For the cancer therapy, it usually suffers from a few challenges, especially the non-specificity which frequently do harm to the normal organs. Whilst marvellous attempts have been devoted to search for more effective cancer treatments. As a developing specific cancer therapy, an emerging cancer therapy with developable potentialphotothermal therapy (PTT) has drawn considerable attention, mainly relying on the irradiation of PTT reagents to switch light energy into hyperthermia and induce apoptosis of cancer cells.1-3 Among the variety of the PPT reagents, two-dimensional (2D) nanomaterials have drawn remarkable attentions owing to their ultrathin structure and outstanding physicochemical properties, which have given rise to numerous potential applications.4 Especially, the 2D materials can be regarded as the efficient nanocarriers for the cancer therapy, for instance, layered double hydroxides,5-7MoS2,8 MXenes,9-10 graphene,11 etc. Among which, the manganese dioxide (MnO2) has attracted the attention by its exclusive characteristics, which is responsive to H+ or glutathione (GSH) to generate Mn2+ ions, extensively improving the performance of T1-magnetic resonance imaging (MRI) for tumor detection.12 Therefore, manganese dioxide has been widely applied for the cancer therapy as a nanocarrier (e.g. such as MnO2 nanosheets,13 hollow MnO2 spheres14). However, the capability of MnO2 as a competent agent for cancer therapy has been disregarded. Recently, oxygen vacancy (OV) has been proved to be able to work as the trapping site for photogenerated electron and tends to induce the occurrence of intermediate energy level, which leads to the enhancement of the performance.15-17 This theory has been receiving much attention in various fields,18-19 but its potential in biomedical area has been rarely reported.20 Inspired by this, as a paradigm, manganese dioxide with abundant OV and good biocompatibility was selected. Herein, we delicate design and construct an intelligent platform based on the ultrathin MnO2 nanosheet with abundant OV (denoted simply as MnO2) for highly efficient photothermal therapy and photoacoustic imaging under the near infrared irradiation. This ACS Paragon Plus Environment

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outstanding performance is attributed to the vacancy on the MnO2 verified by both extended Xray absorption fine structure (EXAFS) data and density functional theory (DFT) calculation result. The DFT calculations reveal that the direct band gap semiconductor MnO2 can be changed into indirect band gap semiconductor with intermediate energy levels resulted from the OV, which is beneficial for facilitating the photothermal conversion performance. Meanwhile, owing to the performance of acidic H2O2-responsive, the ultrathin nanosheet can be reduced into Mn2+ as a MRI contrast agent, while MnO2 can also be regarded as an agent for the photoacoustic imaging agent so as to achieve the dual-modal imaging. Therefore, this work extends the tactic for this unique NIR-mediated ultrathin MnO2 nanosheet for highly efficient PTT.


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Experimental Part Production of the ultrathin MnO2 nanosheets The ultrathin MnO2 nanosheets (denoted simply as MnO2) were fabricated by one-step hydrothermal reaction method. Briefly, 2 mmol KMnO4 was added to 40 mL solvent (DI water) under mechanical stirring. Subsequently, the above solution was moved into a Teflon-lined autoclave (100 mL). After that, we elevated the temperature to 180 °C for 2 h. Then, the sample of MnO2 can be obtained and further washed with deionized water for a few times. Finally, the samples were dried under vacuum at 60 °C. Production of ML-MnO2 The multi-layered MnO2 (denoted as ML-MnO2) was produced by a moderate method. Briefly, commercial manganese dioxide powder (10 mg) was supplemented into 10 mL solvent, followed by sonication (200 w) in ice water for 10 h. The solid ML-MnO2 would be gathered via centrifugation and dried under vacuum at 60 °C. The cytotoxicity of samples experiments The cytotoxicity of MnO2 and ML-MnO2 were evaluated using cancer cell (HeLa). Briefly, cells were cultured with diverse concentration of MnO2 or ML-MnO2 for 24 h in the 96-well plate and then were added the mixture solution (CCK-8: DMEM =1:10). The viability of HeLa cell was analyzed as the fraction of wells absorbance which was measured using a Thermo Multiskan FC mulitplate photometer. The H&E apoptosis staining of tumors and various organs were investigated in the Wuhan Google Biological Corporation and their pictures were obtained using a fluorescence microscope. In vivo experiments All animal procedures comply with institutional animal regulations. The subcutaneously of each mouse were seeded tumor via injection 200 μL suspension solution of HeLa cells (2106). After two weeks, the animals were randomly divided into three teams (n = 5) with different treatment (dose: 10 mg/kg) until the size of tumor grow equal to 100 mm3: (1) PBS; (2) MnO2; (3) MnO2 +NIR (irradiation the tumor sites with 808 nm for 10 min at 3 h after intravenous injection, only one time). Subsequently, ACS Paragon Plus Environment

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the size of tumor (V) and mass of mice were gauged every 2 days. The size of a tumor was estimated by operating a caliper and assessed by the equation of V = (a  b2)/2 (a stands for the length, b stands for the width). Twenty days after the therapy, the organs and tumor were gathered and fixed in the solution of 4% formaldehyde. The organs slices were stained via dyeing agent (hematoxylin and eosin).


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RESULTS AND DISCUSSION Scheme 1. A schematic illustration for the fabrication of MnO2 toward dual-modal imaging and PTT.

The MnO2 was manufactured via an easy one-step hydrothermal reaction approach. The commercial manganese dioxide powder with multi-layered regarded as the comparison (denoted as ML-MnO2). Detailed information is illustrated in the experimental section. As indicated in the Figures 1a, the XRD pattern of MnO2 reveals its good crystallization, corresponding to the standard PDF card (86-0666).19 As a comparison , all diffraction peaks of the ML-MnO2 are well indication to MnO2 crystallites (PDF card 50-0866) (Figure S1). Whilst, compared with ML-MnO2, the MnO2 nanosheet exhibited good water dispersibility (Figure S2).


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Figure 1. (a) XRD pattern. (b) TEM image (the inset displays the HR-TEM image). (c) EDX maps. (d) Mn 2p XPS spectra for MnO2 sample. The morphology of MnO2 and ML-MnO2 were first investigated by transmission electron microscopy (TEM) images. The geometry of the MnO2 nanosheet is a kind of irregular flower-like structures. This morphology of MnO2 with the size of around 200 nm was constructed with fold ultrathin nanosheets2122(Figure

1b and S3), while the ML-MnO2 sample reveals the relatively similar size of 200 nm (Figure

S4). To confirm the stability of the MnO2, we incubated the MnO2 with H2O2 for 3 h, and the TEM results revels no significant change of the nanosheet morphology (Figure S5). Subsequently, the high-resolution TEM (HRTEM) image evidently monitored the spacing of lattice (d=0.253 nm), matching to the (101) facet in MnO2 (inset of Figure 1b). Whilst, the homogeneous spatial scattering of O, Mn, and K elements for MnO2 by the quantitative energy dispersive X-ray (EDX) maps was convinced (Figure 1c). To further


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explore the thickness of the sample, atomic force microscopy (AFM) was utilized. As indicated in Figures S6, the thickness of MnO2 was about 1.2 nm, in fine accord with the TEM findings. In contrast, it can be found that the thickness of ML-MnO2 was over 60 nm (Figure S7), which is 50 times higher than that of MnO2. The AFM result can verify that the MnO2 we fabricated is an ultrathin nanosheet. To attest chemical elements and the corresponding valence states of MnO2, the X-ray photoelectron spectroscopy (XPS) was engaged. For the survey XPS spectrum (Figure S8a), the strong Mn, O and K signals indicate the presence of Mn, O and K elements, which is consistent with the EDX mapping. As exhibited in Figure S8b, two peaks were viewed (from 635 to 660 eV), which can be accredited to Mn 2p3/2 and Mn 2p1/2. Compared with ML-MnO2, the two prominent peaks of the MnO2 are shifted to lower energy with approximately 0.7 and 0.5 eV, respectively, which may be the appearance of lower valence state. This is usually caused by the OVs.23 More details illustrated by a peak-fitting for this main two peaks of MnO2 (Figure 1d). Especially, two peaks (654.61 eV, 643.21 eV) are ascribed to Mn4+. The other peaks centered at 653.58 and 642.16 eV are assigned to Mn4+ near the OV.24 The ratio of Mn4+ near oxygen vacancies: Mn4+ was around 0.41: 0.59. Whilst, in the O 1s spectra (Figure S9a), the peak (529.90 eV) is ascribed to the lattice oxygen. Another peak (531.58 eV) is appointed to the oxygen species of surface-adsorbed.18 In addition, in the K 2p spectra (Figure S9b), two peaks at 295.4 and 292.6 eV are appointed to K (2p1/2 and 2p3/2, respectively).19 In addition, to confirm that degradation of MnO2 has no significant effect on the oxygen vacancy (incubation with H2O2 for 3h), the XPS was further applied. It can be found that the ratio of Mn4+ near oxygen vacancies: Mn4+ was around 0.407: 0.593 (the ratio value 0.686). Compared with pristine MnO2 sample (0.41:0.59  0.695), this MnO2 after incubation with acidic H2O2 reveals no considerable decrease (Figure S9c and S9d). Specifically, two small peaks (641.09 and 652.6 eV) were observed, which are appointed to Mn2+ 2p3/2 and Mn2+ 2p1/2, respectively25 (Figure S9c). This can verify that the generation of Mn2+ in this system, which can be applied as the MRI contrast. Moreover, X-ray absorption fine structure (XAFS) and Raman spectroscopy were further utilized to analyze the atomic structure and OV for the MnO2 and ML-MnO2 samples.19, 26 The Mn K-edge XANES data and the EXAFS k-space result of ML-MnO2 are similar with the MnO2 ACS Paragon Plus Environment

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(Figure S10). It is obvious that the peak of MnO2 has lower energy than that of ML-MnO2, indicating Mn with lower average oxidation state caused by the defect, which can further verify the existence of OV of MnO2.19 This can also supported the XPS data (Figure 1d). In addition, compared with ML-MnO2 sample, the MnO2 has different arrays of local atomic around Mn atoms (Figure 2a and 2b). For MnO2 sample, the EXAFS spectra of Mn display double peaks in R-space spectra, which can be ascribed to the Mn-O and Mn-Mn shells, respectively.19, 27 Compared with ML-MnO2, MnO2 exhibits lower the two peaks shift (Mn-O and Mn-Mn). In addition, the Raman spectra of MnO2 and ML-MnO2 samples are presented (Figure 3a and S11). The peak (650 cm−1) can be appointed to the symmetric stretching vibrations of Mn−O.17 Interestingly, the MnO2 sample exhibits lower Raman shifts (637 cm–1), which ascribes to the influence of OV.18, 26 These results can vividly confirm the MnO2 sample with OV.

Figure 2. (a) Mn K-edge oscillation and b) EXAFS spectra of ML-MnO2 and MnO2, respectively.

The optical absorption nature was analysed with the UV-vis-NIR absorption spectra. Compared with the ML-MnO2, the absorption of MnO2 at 808 nm has been obviously enhanced, which is greatly favourable for biomedical applications (Figure S12). Furthermore, as shown in Figure S13, it can be found that the Zeta potential value of MnO2 is around –20 mV in various pH environment. In addition, the Zeta potential of ML-MnO2 and MnO2 are –43.7 mV and –24.3 mV in the water solution. Moreover, N2 physisorption analysis (Figure S14) revealed the BET high ACS Paragon Plus Environment

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surface area of 127.9 ± 5.5 m²·g–1 for MnO2. In comparison, the ML-MnO2 sample showed a low BET surface area of 6.3 ± 0.4 m²·g–1. The larger surface area indicated that MnO2 has huge potential as a nanocarrier.

Figure 3. (a) Raman spectrum for MnO2. (b) The concentration of dissolved O2 in H2O2 solutions (100 µm) with various concentrations of MnO2. (c) Δ1/T1 and (d) T1-weighted versus Mn concentration MR images for MnO2 in different pH solution. (e) Temperature elevation of the H2O and MnO2 with different concentrations (1.0 W/cm2, 10 min). (f) The photothermal heating curve of the MnO2 for three lasers on/off cycles.


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As far as we are concerned, the environment inside the solid tumors is acid (pH  6.5)28 and hypoxia, which is attributed to insufficient blood supplement, leading to the obvious rise of H2O2 level within tumors.29-30 Under the acid circumstance, H2O2 can be oxidized to O2, while MnO2 will be degraded to Mn2+. As the enhancement concentration of MnO2, the volume of the generated O2 increased obviously (Figure 3b), strikingly verifying the outstanding performance of MnO2 to catalyze H2O2 into O2. These results strongly indicated that the MnO2 can effective modulate the hypoxic tumor microenvironment. Moreover, since MnO2 can be degraded into Mn2+ in tumor microenvironment (acid solution of H2O2), MnO2 may be regarded as a T1 agent of magnetic resonance imaging (MRI). Therefore, MRI was further utilized to analysis the potential of MnO2 as an MRI agent. A remarkably enhanced pH-dependent brightening effect of MnO2 sample was observed with the decrease of pH (from 7.4 to 5.5) (Figure 3c and 3d). The relaxivity of MnO2 sample at various pH value were estimated to be 0, 5.48 and 9.81 mM−1 s−1, respectively. The rather low relaxivity (r1) of MnO2 (pH 7.4) attribute to the high valence (Mn4+) and is shielded paramagnetic centers inaccessible to H2O molecules.31 Importantly, under pH 6.0 and 5.5, the r1 value measured increased intensely from 5.48 to 9.81 mM−1 s−1, because of the MnO2 reduced into Mn2+ (Figure 3c).32 These results reveal that the MnO2 can be served as a superb agent of MRI for pHresponsive cancer diagnosis system. Recently, MnO2 has been studied in relation to nanocarriers of drug molecule for cancer therapy,14 but rarely and directly as PTT agent. On account of the good absorbance of MnO2 in the NIR region, we assume that it has potentials to induce the photothermal activity. To investigate their photothermal performance, MnO2 and ML-MnO2 at varied concentrations (from 25 to 1000 μg/mL) were irradiated with NIR laser (Figure 3e and S15). It can be found that the solution of MnO2 (1 mg/mL) temperature reached 74.5 oC under irradiation. However, the temperature of ML- MnO2 (1 mg/mL) and H2O show moderate change (48.8 oC and 30.5 oC). Whilst, to verify the photothermal capacity of MnO2 after the incubation of H2O2, the photothermal curves of MnO2 with different incubation time were measured. As shown in Figure S16, it can be found that the photothermal temperature shows no significant change. To estimate the MnO2 photothermal ACS Paragon Plus Environment

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stability, the recycling temperature alterations were measured. The photothermal capability of the MnO2 shows negligible change during the recycling (Figure 3f). To precisely evaluate the photothermal performance of the MnO2 and ML-MnO2, the photothermal conversion efficiency (η) of these samples were estimated (Figures S17-S19, more detailed in SI), revealing a remarkably high η of 62.4% for MnO2, which is much higher than that of the ML-MnO2 (16.5%). Moreover, this result is also higher than most reported photothermal agents (table S1), such as MnO2 nanosheets33 MHPCNs−SS−PGA−FA,34 PEG-MoOx NPs,35 WO2.9,36 AuNR@G37 and SPNI-II.38

Figure 4. (a) Optimized geometry of model MnO2. The color for each element is labeled. (b) Band structure of model ML-MnO2 (Eg = 1.374 eV). The valence band maximum and conduction band minimum are highlighted, and the band gap energy is listed in the bracket. (c) Band structure of model MnO2 (Eg = 0.235 eV). (d) Density of states for model MnO2.


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To further scrutinize the enhancement of photothermal conversion for MnO2 deriving from the OV, DFT calculations were performed on MnO2, taking ML-MnO2 as a comparison. Detailed information for the model construction and computational method are listed in the SI. The optimized geometries for model MnO2 and ML-MnO2 are displayed in Figure 4a and Figure S20, respectively. Thus, the band structures for both ML-MnO2 and MnO2 are calculated (Figure 4b and Figure 4c), respectively. The band gap energy of ML-MnO2 is evaluated to be 1.374 eV, suitable for the 808 nm laser used in this work. Moreover, both valence band maximum and conduction band minimum of ML-MnO2 locate at the G-point, indicating that ML-MnO2 is a direct band gap semiconductor. Alternatively, the introduction of OV in MnO2 results to a series of intermediate energy levels in the forbidden zone, which can decrease the activation energy for photogenerated electron-hole recombination from 1.374 eV to 0.235 eV. According to the Arrhenius equation, the nonradioactive rate has an inverse exponential relation with the activation energy.39-40 Therefore, the intermediate energy levels deriving from the OV facilitate the photothermal conversion by increasing the nonradiative rate. Moreover, the valence band maximum of MnO2 locates at the F-point while the conduction band minimum locates at the G-point, revealing that the MnO2 is an indirect band gap semiconductor. In indirect band gap semiconductor, a photon is absorbed after the electron gose through an intermediate state and transfer momentum to the crystal lattice, in other words, phonon, which is a form of heat.41 Therefore, the indirect band gap of MnO2 benefits the photothermal conversion, the density of states for both MnO2 and ML-MnO2 are displayed in Figure 4d and Figure S21, respectively. The intermediate energy levels of MnO2 are composed of Mn-3d and O-2p orbitals, indicating that the intermediate energy levels derive from the breaking of Mn-O bond, which is resulted from the OV.


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Figure 5. The viabilities of HeLa cells cultured with (a) MnO2 and (b) ML-MnO2 with various concentrations. (c) Fluorescence imaging of control, MnO2 and ML-MnO2 (50 μg/mL) without or with NIR therapy. Live HeLa cells are stained with Calcein AM/PI, while dead are stained with PI. Motivated by good photothermal conversion performance of MnO2, we further examined the photothermal therapy effect of these samples in vitro. To investigate the internalization behavior of MnO2, a photosensitizer (red fluorescence) DOX42 was selected to label MnO2, rendering the nanosheet can be facilely spoted via a confocal laser scanning microscopy (CLSM). The strong red fluorescence intensity can be detected inside the HeLa cell and mainly accumulated in the cytoplasm (Figure S22). In addition, we exaimed the efficiency of MnO2 and ML-MnO2, respectively. HeLa cells were incubated with the ACS Paragon Plus Environment

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MnO2 and ML-MnO2 at concentrations range from 5–50 μg/mL after the incubation of 24 h, and then treated with NIR for 10 min. Without irradiation, MnO2 was found to have minimal effect on cell viability (Figure 5a). As a comparison, the ML-MnO2 was observed to have appearent effects on cell viability (Figure 5b). After the irradiation treatment, the efficacy of MnO2 was shown to be considerably enhanced. In contrast, the ML-MnO2 exhibited negatively efficacy at same condition (Figure 5a and 5b). Moreover, to visualize anticancer efficacy, HeLa cells were stained via both calcein-AM and propidium iodide (Calcein-AM/PI).43 There is strong green fluorescence observed in living cell with MnO2 (Figure 5c). As a comparison, only a few living cells can be found with ML-MnO2, which fiercely demonstrated the outstanding biocompatibility of MnO2. Whilst, the strong red fluorescence of cells treated with both samples can be observed with irradiation for 10 min. These results are consonant with the CCK-8 results, which strongly proved the good therapy efficacy of MnO2 toward cancer cells. Given the exciting in vitro results, the anticancer effect of MnO2 was further examined in vivo. To observed the accumulate behaviour of MnO2, a photosensitizer indocyannie green (ICG) was selected to label MnO2 and the small-animal imaging system was utilized to image HeLa-tumor-bearing mice with an intravenous injection of the ICG-labeled MnO2. There is strong ﬂuorescence signal of ICG-labeled MnO2 accumulated in the tumor sites after the 3 h of post-injection (Figure S23 and S24). There is still strong fluorescence intensity in the tumor site after the i.v.injection from 3 h to 48 h, which could be assigned to the EPR effect of nanomaterials.44 Recently, photoacoustic imaging has become one of the most promising diagnostic tools, as a result of its plenty advantages such as deep detection, high sensitivity and spatial resolution.22 Since MnO2 can exhibit outstanding photothermal performance, the potential of MnO2 as an in vivo photoacoustic imaging agent was further estimated. The picture reveals that a strong PA signal can be discovered at the tumor site after the injection of MnO2 (Figure 6b). In contrast, there is no obvious PA signal without the injection of MnO2 (Figure 6a).


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Figure 6. (a-b) The PAI of the HeLa tumor-bearing mice before and after i.v. injection of MnO2 (10 mg/kg). (c) Infrared thermal images of HeLa tumor-bearing mice after i.v. injection with PBS and MnO2 with NIR therapy (1.0 W/cm2, 10 min). (d) Relative tumor growth, (e) body weight curves, and (f) the representative images after indicated treatments (n = 5, ***P < 0.001). (g) Histopathological analysis of organs and tumors from three groups treated with Control, MnO2 and MnO2 +NIR, respectively.

Furthermore, we probed the in vivo PTT tests by the i.v. injection of MnO2. HeLa tumorbearing mice have been separated into two groups: Control with NIR laser and MnO2 with NIR


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laser (dose of 10 mg/kg). It is easy to find that the surface temperature of the MnO2 + NIR laser group was elevated from 14 to 60 °C with the continuous NIR therapy of 10 min, which was adequate to kill the cancer cells. As a comparison, the tumor temperature of mice group under the same irradiation reveals negligible temperature variation (Figure 6c). Furthermore, we measured the tumor volumes of the mice every 2 days via a digital calliper. As expected, the tumors of MnO2 + NIR treatment group were entirely vanished, and without reoccurrence under the 20 th observation (Figure 6d). In contrast, the tumor volumes in the Control, and MnO2 group grow fast after the treatments. Furthermore, all the mice reveal insignificant weight variations, proving no obvious effects of these therapies (Figure 6e). These results of therapy efficacy can be further validated by representative tumor images at the 20 th day (Figure 6f). To further realize the therapeutic effect of PBS, MnO2 and MnO2+NIR groups, the main organs (heart, lung, liver, spleen, kidney) and the tumor tissues were scrutinized via hematoxylin and eosin (H&E) staining. It is not hard to find that there is no apparent impairment to the main organs, while there was serious necrosis in the tumor tissue after the MnO2 +NIR treatment. These data exhibit the outstanding therapeutic potential of MnO2 nanosheet for imaging-guided cancer therapy.

CONCLUSIONS In summary, a novel dual-responsive (H2O2 and pH value) MnO2 with oxygen vacancy mediated dual-modal imaging-guided cancer therapy has been developed. Compared with the ML-MnO2, the MnO2 demonstrate an outstanding photothermal conversion performance. The remarkable PTT performance can be attributed to the abundant vacancy of MnO2, which was confirmed by the EXAFS results and the density functional theory (DFT) calculation. As a result, this study presents a promising platform for the biomedical applications.

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Supporting Information. Supplementary Figures and Table. Figure S1-24, Table S1. This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]; [email protected]. Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT The authors are very appreciative for the financial support from National Natural Science Foundation of China (21805293 and 31701215). We further thankful for the financial support from the Joint NSFC-ISF Research Program by National Natural Science Foundation of China and Israel Science Foundation (51561145004). We also appreciate the support from Director Foundation of the Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (Grant No. 2018-GSY).


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Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by Ultrathin MnO2 Nanosheet Li Wang,a,b Shanyue Guan,*a Yangziwan Weng,a,b Si-Min Xu,c Heng Lu,a Xiangmin Menga and Shuyun Zhou*a aKey

Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of

Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China bUniversity cState

of Chinese Academy of Sciences, Beijing 100190, P. R. China

Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology,

Beijing 100029, P. R. China.

The table of contents entry

An MnO2 with abundant oxygen vacancy is synthesized via a facile hydrothermal method, which have superior photothermal conversion performance, can be potentially applied in dual-modal imaging and photothermal therapy.


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Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by

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