Mesoporous Manganese Dioxide Coated Gold Nanorods as a

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Materials and Interfaces

Mesoporous manganese dioxide coated gold nanorods as a multi-responsive nanoplatform for drug delivery Zheng Zhang, and Yuanhui Ji Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.8b05331 • Publication Date (Web): 01 Feb 2019 Downloaded from http://pubs.acs.org on February 3, 2019

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Industrial & Engineering Chemistry Research

Mesoporous manganese dioxide coated gold nanorods as a multi-responsive nanoplatform for drug delivery Zheng Zhang1, Yuanhui Ji1* 1 Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, School of Chemistry and

Chemical Engineering, Southeast University, Nanjing, 211189, People’s Republic of China *Authors for correspondence: E-mail: [email protected]; [email protected]

ABSTRACT: Nanomaterials can offer a chance to integrate many of excellent physical and chemical performances into a single carrier for smart responsive drug delivery. Herein, gold nanorods/mesoporous manganese dioxide (Au/MnO2) hybrid nanoparticles were prepared to combine the photothermal effect of gold nanorods (AuNRs) with glutathione (GSH)-responsive and pH-responsive performances of MnO2. The near-infrared (NIR) responsive constituent of Au/MnO2 nanoparticle was AuNRs. Doxorubicin hydrochloride (DOX), a widely used anticancer drug, was loaded into the Au/MnO2 hybrid nanoparticle via electrostatic force, hydrogen bond and physical absorption with a drug loading up to 99.1%. The results revealed that the mesoporous MnO2 was degraded in the media with high concentrations of GSH and acid microenvironment.

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The Au/MnO2 nanoparticles displayed satisfying drug release kinetics (ca. 47% of loaded drug released in 12 h) and showed excellent GSH-responsive, pH-responsive and NIR-responsive performances. This multi-responsive nanoplatform is expected to have wide biomedical application for cancer therapy such as photothermal therapy, drug delivery, and tumor microenvironment improvement.

Keywords: Core-shell nanoparticles, Gold nanorod, Mesoporous manganese dioxide, Degradation, GSH-/pH-/NIR-responsiveness, Drug delivery

1. INTRODUCTION Nanomaterials often exhibit excellent performances, which offers a chance in integrating many of unique physical and chemical properties into a single platform for smart responsive drug delivery.1-3 In particular, the multi-responsive drug delivery nanoplatform is one of the most promising ways to improve the therapeutic efficacy of cancer treatment due to its intelligent properties.4 Recently, a large number of nanoscale drug carriers have been prepared to improve the therapeutic efficacy of tumors, such as polymeric nanomaterials,5 inorganic nanomaterials,6 and gold nanoparticles.7,8 Among these drug delivery carriers, gold nanorods (AuNRs) have been proved to be a potentially valuable nanoplatform for tumor treatment 9,10 because of their excellent optical properties,11 tunable localized surface plasmon resonance (LSPR) and photothermal effects.12,13 It is well known that the LSPR maximum wavelength of the AuNRs is in the range from 650 nm to 950 nm, which is generally considered a desirable NIR window owing to the advantage of deep-tissue penetration and the harmless to the surrounding healthy tissues.14 More importantly, the lattice interaction of AuNRs will be changed when they absorb the photon energy of NIR, and then the AuNRs can transfer the absorbed light energy into thermal energy. Namely,


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the AuNRs show the photothermal effects that produce a large amount of heat when irradiated by the NIR laser. Therefore, as localized heat sources, the AuNRs have attracted much attention in various fields including drug delivery,15 photothermal therapy,16 and thermal imaging detection.17 However, the main limitation of AuNRs is their low drug loading because the structures of AuNRs are rod-like resulting in relatively low surface area. In addition, the AuNRs can be reshaped from rod to sphere under the sustained irradiation of NIR laser due to their poor stability.18 The photothermal transition effect of AuNRs often decreases under the NIR sustained irradiation. In order to overcome these two disadvantages, AuNRs were often coated with inorganic materials or organic materials as a novel cancer thermo-chemotherapeutic platform.19 The tumor microenvironment is an important influencing factor in many approaches of cancer treatment,20,21 which is often featured with low pH values, hypoxia, high concentration of H2O2 and glutathione (GSH).22-24 Experimental studies explained that GSH plays a pivotal role in the physiological processes of genetic material synthesis and immune.25,26 The intracellular level of GSH are much higher (100-1000 fold) than that in the extracellular fluids,27 and the concentration of GSH in cancer cells is at least four times higher than that in normal cells due to the hypoxia.28 Furthermore, MnO2 can react with GSH or H+ existing in the microenvironment of tumors. Thus, GSH has gotten great attention in constructing drug delivery platform in cancer cells and a series of GSH-responsive controlled-release nanoparticles have been reported.29-31 Even though MnO2 can be decomposed into Mn2+ ions, it excreted rapidly by kidney without long-term toxicity. In addition, MnO2 can also trigger the decomposition of hydrogen peroxide into water and oxygen to alleviate hypoxia of tumors, which is favorable to improve the therapeutic effect of some cancers such as radiotherapy and photodynamic therapy and so on.32–36 However, previously reported MnO2 nanostructures are mostly nanosheets or covering the surface of other types of nanoparticles.


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Currently, nanomaterials with mesoporous structures have been proven to be excellent drug delivery carriers to load drug agent.37,38 To the best of our knowledge, mesoporous MnO2 coated gold nanorods as a multi-responsive drug delivery nanoplatform have not been reported. Herein, this work developed a novel biodegradable nanoparticle to combine the photothermal effect of AuNRs with the GSH-responsive and pH-responsive performances of MnO2 in a single nanoplatform. The route to prepare Au/MnO2 nanoparticles with high drug loading, excellent GSH-responsive, pH-responsive and NIR-responsive performance is shown in Scheme 1. Firstly, Au/MnO2 nanoparticles were prepared by reaction between KMnO4 and ethanol on the surface of AuNRs. As a NIR-responsive component, the AuNRs can produce heat under the laser irradiation, and then it can be used as the power for the release of the anticancer drug. As a widely used anticancer drug, doxorubicin hydrochloride (DOX) with positive charge has been selected as a model drug. DOX was loaded into the mesoporous MnO2 via electrostatic force, hydrogen bond, and physical absorption. MnO2 was degraded and then released the loaded drug in the media with high concentrations of GSH and acid environment. In particular, we discussed the photothermal conversion efficiency and drug release kinetics of Au/MnO2 nanoparticles. In general, an intelligent drug delivery carrier has attracted much more attention due to its unique properties such as high drug loading efficiency, multi-responsiveness, and favourable degradability which is expected to have wide biomedical application for cancer therapy such as photothermal therapy, drug delivery, and tumor microenvironment improvement.


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Scheme 1. Scheme of preparation of Au/MnO2 nanoparticles. 2. EXPERIMENTAL SECTION 2.1. Materials Tetrachloroauric (III) acid tetrahydrate (HAuCl4•4H2O, Sinopharm Chemical Reagent Co., Ltd, China), cetyltrimethyl ammonium bromide (CTAB, Tianjin Kemio Reagent Co., Ltd, China), Lascorbic acid (VC, Tianjin Kemio Reagent Co., Ltd, China), silver nitrate (AgNO3, Aladdin Reagent Co., Ltd, China), sodium borohydride (NaBH4, Sinopharm Chemical Reagent Co., Ltd, China), doxorubicin hydrochloride (DOX, Aladdin Reagent Co., Ltd, China), potassium permanganate (KMnO4, Shanghai Lingfeng Chemical Reagent Co., Ltd, China), and ethyl alcohol absolute (CH3CH2OH, Tianjin Kemio Reagent Co., Ltd, China). All reagents were analytically pure without further depuration. Ultrapure water (18.25 MΩ) was obtained through thermo purification system. 2.2. Preparation of AuNRs Nanoparticles The AuNRs nanoparticle was synthesized according to a published procedure with some modifications.39 HAuCl4 (0.1 mL, 25 mM) and CTAB solution (10 mL, 1 mM) were mixed at 28


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oC.

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Frozen solution of NaBH4 (0.6 mL, 10 mM) was added into the mixture under stirring (800

rpm) for 2 min. Prepared seeds dispersion stayed at 28 oC for 2 h. CTAB solution (100 ml, 0.1 mM), AgNO3 solution (2.3 mL, 4 mM) and HAuCl4 aqueous solution (2 mL, 25 mM) were mixed in a round-bottomed flask. L-ascorbic acid solution (0.7 mL, 0.0788 mM) was added into the mixture with stirring. After the L-ascorbic acid was added, the solution became colorless quickly, the formed seeds dispersion (1 mL) was added immediately and the mixed solution stayed at 28 oC

at least 6 h.

2.3. Preparation of Au/MnO2 Nanoparticles The prepared AuNRs dispersion was treated with centrifugation. The volume of centrifuged AuNRs were up to 100 mL by adding water. NaOH solution (1 mL, 100 mM) and KMnO4 (40 mg) were added into the AuNRs suspension. CH3CH2OH was added into the mixture within 60 min. After that, the mixture was kept with general stirred at 30 oC for 24 h. The temperature increased to 50 oC and kept for another 6 h. The color of the solution became brown from purple-red. The reacted sample was centrifuged to remove the upper solution and retain the precipitate. 2.4. Characterization of Au/MnO2 Nanoparticles The UV-Vis-NIR spectrum of Au/MnO2 nanoparticles was achieved by spectrophotometer (Cary series, Agilent). The transmission electron microscopy (TEM) images were obtained by Tecnai G2 20 (FEI) with a maximum accelerating voltage of 200 kV. Field-emission scanning electron microscopy (FESEM) image was characterized by Quanta 250 FEG with the clean silica wafers. The surface potential of nanoparticles and statistic size of the nanoparticles were obtained by the zeta-sizer analyzer (NanoZS90, Malvern). Each sample was measured for 3 times to obtain an average value. The XRD pattern was determined using an X-ray diffractometer (D8Advance, Bruker). The Raman spectra of Au/MnO2 nanoparticles was measured using Raman imaging


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microscope (DXRxi, Thermo Fisher) and the excitation wavelength of the laser was 532 nm. The N2 adsorption/desorption isotherms of Au/MnO2 nanoparticle were observed on a gas adsorption instrument (ASAP2020, Micromeritics). Brunauer-Emmett-Teller (BET) and Barrett-JoynerHalenda (BJH) methods were applied to calculate the surface area, pore size, and pore volume of nanoparticles respectively. The temperature images of Au/MnO2 nanoparticles dispersion were characterized by IR camera (TG165, FLIR). 2.5. Photothermal Effect Evaluation and Drug Release Experiment For the photothermal effect evaluation, dispersing liquid of Au/MnO2 nanoparticles was irradiated by the NIR laser with different power density (808 nm, 1 Wcm-2, 2 Wcm-2, and 4 Wcm2).

The photothermal test was obtained by an IR camera and temperature variation of Au/MnO2

nanoparticles under the NIR laser irradiation. For the experiment of drug loading and release, the anticancer drug was loaded into the Au/MnO2 nanoparticles by mixing DOX solution (2.5 mL, 2.0 mg/mL) with centrifuged nanoparticles for 12 h. After drug loading, the DOX-loaded nanoparticles (Au/MnO2-DOX) were collected by centrifuging the dispersion. The collected sample was washed 3 times with water to remove the DOX which was not loaded into the Au/MnO2 nanoparticles. The absorption value of DOX (481 nm) was determined by UV-Vis-NIR spectrophotometer. The amount of dissociative DOX was calculated based on the standard curve of concentration-absorption value. The following equations were used to calculate the DOX content and drug loading efficiency of Au/MnO2 nanoparticle:40,41 Drug content (mg per 10 mg sample) = (DOX fed - supernatant DOX) / nanoparticles amount × 10 DOX loading efficiency (%) = (DOX fed - supernatant DOX) / DOX fed × 100%


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For the in vitro drug release experiments, GSH solution (1.0 mL), phosphate buffer solution (PBS, pH=7.4), and acetate buffer solution (ABS, pH=4.5) were added to the dialysis bag respectively. After that, the drug-loaded nanoparticles were dispersed in the dialysis bag with different solutions. GSH/PBS solution (12 mL) was added to external environment of the dialysis bag at 37℃. The experimental installation was wrapped with aluminium foil. The samples were irradiated by NIR laser (808 nm) with different power densities. The external liquid of the dialysis bag (3.5 mL) was taken out and added with the same volume of solution every 0.5 h. Each sample was tested for 3 times to obtain an average absorption value by UV-Vis-NIR spectrometer. 3. RESULTS AND DISCUSSION 3.1. Characterization of Au/MnO2 Nanoparticles The preparation processes of Au/MnO2 nanoparticles were investigated by UV-Vis-NIR spectrophotometer. The spectrum of AuNRs, Au/MnO2, and Au/MnO2-DOX was illustrated in Figure 1. The result showed that AuNRs had intensive LSPR peaks (ca. 780 nm) and weak transverse surface plasmon oscillation (ca. 510 nm). A slight red-shift (from 780 nm to 760 nm) appeared in the LPSR peak after AuNRs was encapsulated by mesoporous manganese dioxide shell. The small red-shift (ca. 20 nm) of LSPR peak could also be found after the loading of DOX. The difference in refractive index of each component leads to the red shift of LSPR peak in the preparation of Au/MnO2 nanoparticles.42,43 In addition, the UV-Vis-NIR peak of DOX loaded in the Au/MnO2 nanoparticles also increased significantly (ca. 481 nm). The high absorption value of DOX indicated that the Au/MnO2 nanoparticles have strong loading capacity. Remarkably, the LSPR peak of Au/MnO2-DOX nanoparticles indicated that the NIR responsibility had not subsided after AuNRs coated with mesoporous MnO2 shell and DOX. It is a great significance for the drug controlled release and photothermal therapy of tumors because photons can penetrate biological


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tissues and almost no harm in the NIR region. The Au/MnO2 suspension (Figure 1, inset) was black-brown and black powder after drying (see Figure S1 in the Supporting Materials). There was an obvious color change during the preparation of Au/MnO2 from AuNRs. During the coating process of AuNRs with MnO2, the color gradually changed from purple to yellow-brown and then to black-brown. The above results show that MnO2 was successfully coated on the surface of AuNRs.

Figure 1. UV-Vis-NIR spectrum of AuNRs (dash-dotted line), Au/MnO2 (dashed line) and Au/MnO2-DOX (dotted line) nanoparticles. Inset: photos of Au/MnO2 suspension. To further understand the 3D nanostructure and composition of AuNRs and Au/MnO2 nanoparticles, the results of TEM and FESEM were exhibited in Figure 2. As shown in Figure 2a, the average length of AuNRs was 30±1.0 nm and the average width was 8.0±0.5 nm, respectively. The AuNRs nanoparticles were rod-like and the core-shell structure nanoparticles were clearly observed after being coated with mesoporous manganese dioxide shell (Figure 2b, c). The mesoporous MnO2 was around the surface of AuNRs and the thickness of manganese dioxide shell was ca. 70 nm. The FESEM micrographs of Au/MnO2 nanoparticles (Figure 2d) show that the


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Au/MnO2 nanoparticles are spherical structures and the average diameter of Au/MnO2 nanoparticles are ca. 140 nm. The FESEM observations got the same information like that from TEM. The corresponding EDX spectra of Figure 2d (see Figure S2 in the Supporting Materials) confirmed the existence of Mn and O element which indicated the successful coating of MnO2 shell.

Figure 2. TEM images of AuNRs (a), Au/MnO2 (b, c), and FESEM images of Au/MnO2 (d). In order to study the changes of size and the surface zeta potential during the drug loading procedure preferably, the values of zeta potential and particle size of Au/MnO2 and Au/MnO2DOX were obtained and corresponding results were exhibited in Table 1. The value of zeta potential of Au/MnO2 was ca. -17.1 mV. It may be because the synthetic condition of the MnO2 is alkaline, the -OH was attracted to the surface instead of clean surfaces and a large number of hydroxyl groups were obtained on the surface of Au/MnO2 nanoparticles.44,45 The zeta potential of Au/MnO2 nanoparticles was ca. +13.6 mV after DOX was loaded (Au/MnO2-DOX). The


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change of zeta potential of Au/MnO2 nanoparticles indicated the successful load of positively charged DOX. Size distribution analyses of Au/MnO2 and Au/MnO2-DOX nanoparticles were performed and the corresponding results were exhibited in Figure 3a and Figure 3b. It was observed from Figures that the diameter of Au/MnO2 and Au/MnO2-DOX nanoparticle were ca. 90-170 nm and the size distributions were narrow and similar (Figure 3a, b). Such results were agreed well with the TEM and FESEM observations. Table 1. Zeta potential and nanoparticle size of Au/MnO2 and Au/MnO2-DOX nanoparticles.

Composition

Zeta potential (mV)

Nanoparticle size (d. nm)

Au/MnO2

-17.1

139

Au/MnO2-DOX

+13.6

146

Figure 3. Size distributions of Au/MnO2 (a) and Au/MnO2-DOX (b) nanoparticles. To further elucidate the crystalline structure of manganese dioxide inorganic shell, the Au/MnO2 nanoparticles were characterized by XRD and the results are shown in Figure 4a. As shown in Figure 4a, the sharp peaks in the region of 35°-85° were the characteristic peaks of AuNRs crystal


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structure, and the amorphous hump of manganese dioxide in the region between 15° and 30° was obvious, indicating that the manganese dioxide shell was disordered amorphous structure. It should be noted that the Raman imaging microscope was usually used to analyze the local structure of nanomaterials especially for the poor crystallinity.46 We performed Raman spectroscopy measurements to characterize the local structure of Au/MnO2 nanoparticles. The dispersion liquid of Au/MnO2 nanoparticles was dropped onto aluminum foil substrate, and the excitation wavelength of the laser was 532 nm. It can be obviously to be found from Figure 4b that the Au/MnO2 nanoparticles showed typical Mn-O peak.47 According to previous works, the peaks across the 500-700 cm−1 were suited for α-MnO248 and the above-mentioned sharp peaks belong to MnO stretching mode in [MnO6] octahedral. The [MnO6] octahedral shared edges with opposite octahedra and linked to neighboring [MnO6] octahedral in turn to form (2 × 2) or (1 × 1) tunnels.49 The existence of tunnel structure is not only conducive to the stability of manganese dioxide structure but also conducive to drug loading.

Figure 4. XRD images of Au/MnO2 nanoparticles (a) and Raman spectra of Au/MnO2 nanoparticles (b).


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The N2 adsorption/desorption isotherms of Au/MnO2 nanoparticles have been presented in Figure 5. The isotherms of the sample were classified as type IV (Figure 5a) according to IUPAC classification. The typical H1 hysteresis loop of type IV indicated that the existence of mesoporous structure.50-52 The mesoporous structure enabled Au/MnO2 nanoparticles play a vital role in the intelligent drug delivery carrier because it can improve the drug loading efficiency. The BET surface area of Au/MnO2 nanoparticles was calculated to be 24.84 m2g-1, the total pore volume was calculated to be 0.20 cm3g-1. The BJH pore diameter was calculated to be 31.11 nm and the pore size distribution curve of Au/MnO2 namoparticles was presented in Figure 5b. As we know, the nanomaterials with mesoporous structure provide a promising way to load drug agent.37,38 The mesoporous structure of Au/MnO2 nanoparticles is as important as its own tunnel structure for the loading of antitumor drugs. The unique structures provide the foundation for Au/MnO2 nanoparticles to provide excellent loading capacity for drugs.

Figure 5. N2 adsorption/desorption isotherm of Au/MnO2 nanoparticles (a) and corresponding pore size distribution curve (b). 3.2. Photothermal Effect of Au/MnO2 Nanoparticles In this work, the AuNRs and mesoporous MnO2 were combined as a smart drug carrier. AuNRs offered a serviceable mode to transfer the NIR light energy into heat. As we know, photothermal


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transition efficiency has a great effect on the theranostic therapy and drug release.53,54 To better understand the photothermal conversion efficiency of Au/MnO2 nanoparticles, the temperature images of Au/MnO2 nanoparticles were obtained by an IR camera when the suspension under NIR lasers irradiation with different power densities (808 nm, 1 Wcm-2, 2 Wcm-2, and 4 Wcm-2). As shown in Figure 6a, the temperature increased quickly and kept stable for the following 60 min when the Au/MnO2 nanoparticles suspension under the NIR laser irradiation. The result indicated that the Au/MnO2 nanoparticles possessed excellent photothermal conversion efficiency. It was worthy to note that the rising speed and the maximum temperature of Au/MnO2 dispersion were related to the power density of the NIR laser. Figure 6b showed the temperature variation of Au/MnO2 nanoparticles during the NIR laser irradiation. As we expected, the temperature of Au/MnO2 nanoparticles increased rapidly and reached a stable state within 10 min when the suspension was under NIR laser irradiation. Hence, it can be suggested that the absorbed energy of Au/MnO2 nanoparticles can be converted to heat energy quickly.

Figure 6. The IR images (a) and the temperature variation (b) of Au/MnO2 nanoparticles suspension under NIR laser irradiation with different power densities (808 nm, 1 Wcm-2, 2 Wcm2, and

4 Wcm-2).

3.3. Drug Loading and Sustained Release


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As a drug nanocarrier, Au/MnO2 nanoparticle has mesoporous and tunnel structure, excellent biodegradability and predominant drug loading. As an effective anticancer drug, DOX was loaded into Au/MnO2 nanoparticles through electrostatic, hydrogen bond and physical absorption with drug loading efficiency ca. 99.1%. The high drug loading efficiency is mainly attributed to the large mesoporous structure, tunnel structure and a large number of hydroxyl groups,39 and the excellent drug loading of Au/MnO2 nanoparticles was also add a great deal of value to the drug controlled release. As shown in scheme 2, the mesoporous MnO2 shell of Au/MnO2 nanoparticles can be reacted with GSH or H+ existing in the microenvironment of tumors. The MnO2 shell can be decomposed into biodegradable Mn2+ ions and drug release can also be achieved at the same time.55 The NIRresponsive drug release experiments were carried out by using a CW semiconductor laser (808 nm). The MnO2 shell can be degraded in the media with high concentrations of glutathione (GSH) and acid environment of tumor55,56 and also could improve the microenvironment of the tumor such as low pH values, hypoxia, high concentration of H2O2 and GSH.57,58

Scheme 2. Scheme of drug release of Au/MnO2 nanoparticles


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The drug release experimental studies were designed to further investigate the GSH-responsive, pH-responsive and NIR-responsive drug release effect of Au/MnO2 nanoparticles. Drug release curves of Au/MnO2 were illustrated in Figure 7. It was observed from Figure 7a that the cumulative release was ca. 25.0% in GSH solution with a concentration of 1 mM within 12 h at 4 W cm-2. The release profiles at 4 Wcm-2 of laser irradiation in GSH solution (5 mM and 10 mM) were also determined. It was found from Figure 7a that the cumulative release was 36.8% and 47.0% in turn. The release profiles of the Au/MnO2 nanoparticles in water was also obtained (water was the control sample). It was almost no measurable drug release from Au/MnO2 nanoparticles. The above results indicated that Au/MnO2 nanoparticles have obvious GSH-responsive performance. Figure 7b showed that the cumulative release of DOX was up to 13.3% in ABS solution (pH=4.5) within 12 h at 4 W cm-2. The release profiles at 4 Wcm-2 of laser irradiation in a PBS (pH=7.4) were also obtained. As expected, there was almost no DOX release. It showed that the drug carrier exhibited excellent pH-responsive performance. The mesoporous MnO2 can cause defects and collapse when it was corroded in GSH/acid media. The generated defects and collapse of MnO2 shell promoted the release performance of Au/MnO2 nanoparticle. The NIR-responsive release experiment was operated to explore the effect of laser intensity on the drug release of Au/MnO2 nanoparticles. It was observed from Figure 7c that cumulative release of DOX reached 35.2% in GSH solution with a concentration of 5 mM within 12 h at 4 W cm-2. The release profiles at 5 mM of GSH solution in different laser intensity (2 W cm-2, 1 W cm-2 and without NIR irradiation) were also determined, the cumulative release achieved maximum value at 32.1% and 27.5%, respectively, which was evidently higher than that without irradiation. The above results proved that Au/MnO2 nanoparticle exhibited a NIR-responsive performance.


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Figure 7. Drug release profiles of DOX from DOX-loaded Au/MnO2 under different GSH conditions (a); DOX release profiles from DOX-loaded Au/MnO2 under different pH conditions (b); Drug release profiles of DOX from DOX-loaded Au/MnO2 under different NIR laser intensity conditions (c). In this work, MnO2 shell has been coated on the surface of AuNRs nanoparticles. The environment of tumour was simulated and the biodegradability of Au/MnO2 nanoparticles in different concentrations of GSH solution and ABS solution was also studied. Mesoporous MnO2 can easily be eroded in GSH and media with low pH. The inorganic shell of Au/MnO2 generated many defects when MnO2 was decomposed in GSH and acid media, which leaded to the collapse of MnO2 and enhanced drugs release property. Figure 8a showed the TEM image of Au/MnO2 nanoparticle after corrosion in GSH (1 mM), revealing the confinement of MnO2 shell became blurred. Moreover, it was noted that the mesoporous MnO2 shell of Au/MnO2 nanoparticles was disappeared after 12 h (GSH=5 mM) as


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revealed in Figure 8b. The TEM image of Au/MnO2 after corrosion in GSH (10 mM) at 37 °C are shown in Figure 8c. It showed the same results as that in the solution with GSH concentration of =5 mM. Figure 8d showed the TEM image of degradative Au/MnO2 in ABS solutions. The result showed that the confinement of MnO2 became vague. The changed morphology of degraded Au/MnO2 nanoparticles showed that the mesoporous MnO2 could be easily dissolved in GSH solutions and ABS. In other words, the prepared Au/MnO2 nanoparticles were easy to be degraded in GSH solution and ABS solution and have potential application prospects in the field of multiresponsive carriers for drug delivery.

Figure 8. TEM images of Au/MnO2 nanoparticles in corresponding suspension solutions under NIR laser (808 nm, 4Wcm-2, 12 h) irradiation, GSH=1 mM (a), 5 mM (b), 10 mM (c), ABS (d). 3.4. Drug Release Kinetics


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The release kinetics of DOX from the multi-responsive Au/MnO2 nanoparticles has been investigated and the cumulative release kinetics were fitted to the empirical equation as shown in Eq. (1): 59,60 Mt/M=ktn

(1)

where Mt represents the cumulative release of the drug; t represents the time of drug release; M represents the total release of the drug from the matrix; n represents the diffusion index, which is often used to characterize the release mechanism; k represents the release constant, which is related to the structure and performance of materials. In this work, we further provided insight into the mechanism of drug release, and the diffusion index was obtained based on the slope of the ln(Mt/M) plot versus lnt. For spherical drug carriers, the drug release kinetics obeys the Fickian diffusion when the diffusion index n is smaller than 0.43. Otherwise, it obeys non-Fickian or anomalous diffusion when diffusion index is in the range from 0.43 to 0.85. When the diffusion index n equals 0.85, the release kinetics is regarded as the Case-II diffusion. The drug release kinetics is considered as the super Case-II diffusion when the diffusion index n is larger than 0.85.61 The values of k, n, and correlation coefficient (R2) of specific DOX release kinetics in different environments were analyzed as listed in Table S1. The correlation coefficients R2 of each data set showed that the experimental data were highly correlated with the fitting curve and had high reliability. The drug release kinetics curves of ln(Mt/M) versus ln t for Au/MnO2 nanoparticles at different GSH conditions were shown in Figure S3, the values of diffusion index n for Au/MnO2 nanoparticles have a sudden shift at the conditions of GSH=1 mM, 5 mM, and 10 mM. As shown in Figure S3, the value of n changed from 0.478 to 0.101 at GSH=1 mM, while the value of n was from 0.454 to 0.350 at GSH=5 mM and the corresponding value was from 0.505 to 0.388 at GSH=10 mM, respectively, illustrating


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that the anomalous diffusion was shifted to Fickian diffusion. Figure S4 showed the drug release kinetics curves of ln(Mt/M) versus ln t for Au/MnO2 at ABS solution (pH=4.5). The diffusion index of n changed from 0.440 to 0.295. It was obviously shown that the diffusion mechanism of Au/MnO2 has an analogous transition, suggesting that the anomalous diffusion was shifted to Fickian diffusion. Figure S5 was the drug release kinetics curve of ln(Mt/M) versus ln t for Au/MnO2 nanoparticles under different NIR laser intensity conditions. It was found that the nonFickian diffusion was transferred to Fickian diffusion, the values of n altered from 0.478 to 0.291 and changed from 0.458 to 0.354. The above results show that the photothermal conversion and anomalous diffusion play an important role in the initial state of MnO2 degrading. After that, MnO2 has been decomposed to water-soluble Mn2+ ions and Fickian diffusion dominated the drug release process. Such behavior may be responsible for the photothermal effect of AuNRs and degradation of mesoporous MnO2 shell. The results of drug release kinetics showed that the excellent photothermal properties and degradation of Au/MnO2 nanoparticles influence the drug release behavior significantly. 4. CONCLUSIONS In this work, a novel multi-responsive drug carrier was prepared by coating mesoporous MnO2 on the surface of AuNRs. The Au/MnO2 hybrid nanoparticles showed excellent GSH-responsive, pH-responsive and NIR-responsive properties. DOX was loaded into the Au/MnO2 hybrid nanoparticles via electrostatic force, hydrogen bond and physical absorption with a high drug loading up to 99.1%. In vitro drug release kinetics illustrated that the loaded DOX was released sustainedly and the mesoporous MnO2 was degraded in the media with high concentrations of GSH and acid microenvironment. The Au/MnO2 nanoparticles displayed satisfying drug release rates and showed excellent GSH-


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responsive, pH-responsive and NIR-responsive performance. The drug release kinetics indicated that the excellent photothermal effect and degradation of MnO2 influenced the drug release of Au/MnO2 nanoparticles significantly. The developed multi-responsive nanoplatform is expected to have potential application for cancer therapy such as photothermal therapy, drug delivery, and tumor microenvironment improvement. ASSOCIATED CONTENT Supporting Information Parameters k, n and R2 determined by Eq. (1) for the DOX release of Au/MnO2 under different GSH conditions, ABS (pH=4.5) solution and different NIR laser intensity. The photograph of Au/MnO2 aqueous dispersion and Au/MnO2 powder after drying. The corresponding EDX spectra of Figure 2d (FESEM) of Au/MnO2 nanoparticles. Plots of ln(Mt/M) versus lnt for the release profiles of Au/MnO2 under different GSH conditions. Plots of ln(Mt/M) versus lnt for the release profiles of Au/MnO2 under ABS (pH=4.5) solution. Plots of ln(Mt/M) versus lnt for the release profiles of Au/MnO2 under different NIR laser intensity conditions. AUTHOR INFORMATION Corresponding Author *Yuanhui Ji: E-mail: [email protected]; [email protected] ORCID Zheng Zhang: 0000-0002-6599-6852 Yuanhui Ji: 0000-0002-3039-4368 Notes The authors declare no competing financial interest.


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ACKNOWLEDGMENTS The authors gratefully acknowledge the financial support for this research from the National Natural Science Foundation of China (Grant No.: 21776046, 21606043), the Fundamental Research Funds for the Central Universities (Grant No.: 2242017R30002), the Six Talent Peaks Project in Jiangsu Province (Grant No.: XCL-079), and the Recruitment Program for Young Professionals (the Thousand Youth Talents Plan). REFERENCES (1) Chen. X.; Zhang. Q.; Li. J.; Yang. M.; Zhao. N.; Xu. F.; Rattle-structured rough nanocapsules

with

in-situ-formed

gold

nanorod

cores

for

complementary

gene/chemo/photothermal therapy. ACS Nano 2018, 12, 5646-5656. (2) Sun. L.; Liu. Z.; Wang. L.; Cun. D.; Tong. H. H. Y.; Yan. R.; Chen. X.; Wang. R.; Zheng. Y.; Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. J. Control. Release. 2017, 254, 44-54. (3) Wang. R.; Zhao. N.; Xu. F.; Hollow nanostars with photothermal gold caps and their controlled surface functionalization for complementary therapies. Adv. Funct. Mater. 2017, 27, 1700256. (4) Zhang. Z.; Wang. L.; Wang. J.; Jiang. X.; Li. X.; Hu. Z.; Ji. Y.; Wu. X.; Chen. C.; Mesoporous silica-coated gold nanorods as a light-mediated multifunctional theranostic platform for cancer treatment. Adv. Mater. 2012, 24, 1418-1423. (5) Chen. W.; Achazi. K.; Schade. B.; Haag. R.; Charge-conversional and reduction-sensitive poly (vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin


22

Page 23 of 31 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


release. J. Control. Release. 2015, 205, 15-24. (6) Yang. P.; Gai. S.; Lin. J.; Functionalized mesoporous silica materials for controlled drug delivery. Chem. Soc. Rev. 2012, 41, 3679-3698. (7) Alkilany. A. M.; Thompson. L. B., Boulos. S. P.; Sisco. P. N.; Murphy. C. J.; Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Adv. Drug Deliv. Rev. 2012, 64, 190-199. (8) 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. (9) Li. Y.; Jin. J.; Wang. D.; Lv. J.; Hou. K.; Liu. Y.; Chen. C.; Tang. Z.; Coordinationresponsive drug release inside gold nanorod@metal-organic framework core-shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy. Nano. Res. 2017, 11, 32943305. (10) Duan. S.; Yang. Y.; Zhang. C.; Zhao. N.; Xu. F.; NIR-responsive polycationic gatekeepercloaked hetero-nanoparticles for multimodal imaging-guided triple-combination therapy of cancer. Small 2017, 13, 1603133. (11) Zhang. L.; Xia. K.; Lu. Z.; Li. G.; Chen. J.; Deng. Y.; Li. S.; Zhou. F.; He. N.; Efficient and facile synthesis of gold nanorods with finely tunable plasmonic peaks from visible to near-IR range. Chem. Mater. 2014, 26, 1794-1798. (12) Aioub. M.; Panikkanvalappil. S. R.; El-Sayed. M. A.; Platinum-coated gold nanorods: efficient reactive oxygen scavengers that prevent oxidative damage toward healthy, untreated cells


23


Page 24 of 31

during plasmonic photothermal therapy. ACS Nano 2017, 11, 579-586. (13) Li. Z.; Huang. H.; Tang. S.; Li. Y.; Yu. X.; Wang. H.; Li. P.; Sun. Z.; Zhang. H.; Liu. C.; Chu. P.; Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy. Biomaterial 2016, 74, 144-154. (14) Wang. X.; Ma. Y.; Sheng. X.; Wang. Y.; Xu. H.; Ultrathin polypyrrole nanosheets via space-confined synthesis for efficient photothermal therapy in the second near-infrared window. Nano. Lett. 2018, 18, 2217-2225. (15) Wang. S.; Zhao. X.; Wang. S.; Qian. J.; He. S.; Biologically inspired polydopamine capped gold nanorods for drug delivery and light-mediated cancer therapy. ACS. Appl. Mater. Inter. 2016, 8, 24368-24384. (16) Wang. X.; Gao. S.; Qin. Z.; Tian. R.; Wang. G.; Zhang. X.; Zhu. L.; Chen. X.; Evans blue derivative-functionalized gold nanorods for photothermal therapy-enhanced tumor chemotherapy. ACS. Appl. Mater. Inter. 2018, 10, 15140-15149. (17) Wang. C.; Xu. C.; Xu. L.; Sun. C.; Yang. D.; Xu. J.; He. F.; A novel core-shell structured upconversion nanorod as multimodal bioimaging and photothermal ablation agent for cancer theranostics. J. Mater. Chem. B. 2018, 6, 2597-2607. (18) Taylor. A. B.; Siddiquee. A. M.; Chon. J. W. M.; Below melting point photothermal reshaping of single gold nanorods driven by surface diffusion. ACS Nano. 2014, 8, 12071-12079. (19) Wang. Y.; Ji. X.; Pang. P.; Shi. Y.; Dai. J.; Xu. J.; Wu. J.; Thomas. B. K.; Xue. W.; Synthesis of Janus Au nanorods/polydivinylbenzene hybrid nanoparticles for chemo-photothermal therapy. J. Mater. Chem. B. 2018, 6, 2481-2488.


24

Page 25 of 31 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


(20) Chen. W.; Lecaros. R. L.; Tseng. Y. C.; Huang. L.; Hsu. Y. C.; Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for headand-neck cancer. Cancer. Lett. 2015, 359, 65-74. (21) Quail. D. F.; Joyce. J. A.; Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013, 19, 1423-1437. (22) Chang. C.; Qiu. J.; O'Sullivan. D.; Buck. M. D.; Noguchi. T., Curtis. J. D.; Chen. Q.; Gindin. M.; Gubin. M. M.; van der Windt. G. J.; Tonc. E.; Schreiber. R. D.; Pearce. E. J.; Pearce. E. L.; Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015, 162, 1229-1241. (23) Swartz. M. A.; Iida. N.; Roberts. E. W.; Sangaletti. S.; Wong. M. H.; Yull. F. E.; Coussens. L. M.; DeClerck. Y. A.; Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer. Res. 2012, 72, 2473-2480. (24) Chung. M.; Liu. H.; Lin. K.; Chia. W. T.; Sung. H.; A pH-responsive carrier system that generates NO bubbles to trigger drug release and reverse P-glycoprotein-mediated multidrug resistance. Angew. Chem. Int. Ed. 2015, 54, 9890-9893. (25) Mortera. R.; Vivero-Escoto. J.; Slowing. II.; Garrone. E.; Onida. B.; Lin. V. S.; Cellinduced intracellular controlled release of membrane impermeable cysteine from a mesoporous silica nanoparticle-based drug delivery system. Chem. Commun. 2009, 14, 3219-3221. (26) Hong. R.; Han. G.; Fernández. J. M.; Kim. B. J.; Forbes. N. S.; Rotello. V. M.; Glutathionemediated delivery and release using monolayer protected nanoparticle carriers. J. Am. Chem. Soc. 2006, 128, 1078-1079.


25


Page 26 of 31

(27) Cheng. R.; Feng. F.; Meng. F.; Deng. C.; Feijen. J.; Zhong. Z.; Glutathione-responsive nanovehicles as a promising platform for targeted intracellular drug and gene delivery. J. Control. Release. 2011, 152, 2-12. (28) Wang. J.; Sun. X.; Mao. W.; Sun. W.; Tang. J.; Sui. M.; Shen. Y.; Gu. Z.; Tumor redox heterogeneity-responsive prodrug nanocapsules for cancer chemotherapy. Adv. Mater. 2013, 25, 3670-3676. (29) Zhang. Q.; Liu. F.; Nguyen. K. T.; Ma. X.; Wang. X.; Xing. B.; Zhao. Y.; Tumor redox heterogeneity-responsive prodrug nanocapsules for cancer chemotherapy. Adv. Funct. Mater. 2012, 22, 5144-5156. (30) Wang. Y.; Nie. J.; Chang. B.; Sun. Y.; Yang. W.; Poly(vinylcaprolactam)-based biodegradable multiresponsive microgels for drug delivery. Biomacromolecules 2013, 14, 30343046. (31) Park. K. M.; Lee. D. W.; Sarkar. B.; Jung. H.; Kim. J.; Ko. Y. H.; Lee. K. E.; Jeon. H.; Kim. K.; Reduction-sensitive, robust vesicles with a non-covalently modifiable surface as a multifunctional drug-delivery platform. Small 2010, 6, 1430-1441. (32) Zhu. W.; Dong. Z.; Fu. T.; Liu. J.; Chen. Q.; Li. Y.; Zhu. R.; Xu. L.; Liu. Z.; Modulation of hypoxia in solid tumor microenvironment with MnO2 nanoparticles to enhance photodynamic therapy. Adv. Funct. Mater. 2016, 26, 5490-5498. (33) Chen. Q.; Feng. L.; Liu. J.; Zhu. W.; Dong. Z.; Wu. Y.; Liu. Z.; Intelligent albumin-MnO2 nanoparticles as pH-/H2O2-responsive dissociable nanocarriers to modulate tumor hypoxia for effective combination therapy. Adv. Mater. 2016, 28, 7129-7136.


26

Page 27 of 31 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


(34) Gordijo. C. R.; Abbasi. A. Z.; Amini. M. A.; Lip. H. Y.; Maeda. A.; Cai. P.; O’Brien. P. J.; DaCosta. R. S.; Rauth. A. M.; Wu. X.; Design of hybrid MnO2-polymer-lipid nanoparticles with tunable oxygen generation rates and tumor accumulation for cancer treatment. Adv. Funct. Mater. 2015, 25, 1858-1872. (35) Prasad. P.; Gordijo. C. R.; Abbasi. A. Z.; Maeda. A.; Ip. A.; Rauth. A. M.; DaCosta. R. S.; Wu. X. Y.; Multifunctional albumin-MnO2 nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response. ACS Nano 2014, 8, 3202-3212. (36) Song. M.; Liu. T.; Shi. C.; Zhang. X.; Chen. X.; Bioconjugated manganese dioxide nanoparticles enhance chemotherapy response by priming tumor-associated macrophages toward M1-like phenotype and attenuating tumor hypoxia. ACS Nano 2015, 10, 633-647. (37) Chen. Y.; Q. Meng.; Wu. M.; Wang. S.; Xu. P.; Chen. H.; Li. Y.; Zhang. L.; Wang. L.; Shi. J.; Hollow mesoporous organosilica nanoparticles: a generic intelligent framework-hybridization approach for biomedicine. J. Am. Chem. Soc. 2014, 136, 16326-16334. (38) Li. Y.; Shi. J.; Hollow-structured mesoporous materials: chemical synthesis, functionalization and applications. Adv. Mater. 2014, 26, 3176-3205. (39) Gorelikov. I.; Matsuura. N.; Single-step coating of mesoporous silica on cetyltrimethyl ammonium bromide-capped nanoparticles. Nano. Lett. 2008, 8, 369-373. (40) Wei. J.; Shi. J.; Wu. Q.; Yang. L.; Cao. S.; Hollow hydroxyapatite/polyelectrolyte hybrid microparticles with controllable size, wall thickness and drug delivery properties. J. Mater. Chem. B. 2015, 3, 8162-8169.


27


Page 28 of 31

(41) Zhang. Z.; Shi. J.; Song. Z.; Zhu. X.; Zhu. Y.; Cao. S.; A synergistically enhanced photothermal transition effect from mesoporous silica nanoparticles with gold nanorods wrapped in reduced graphene oxide. J. Mater. Sci. 2018, 53, 1810-1823. (42) Wu. C. L.; Xu. Q. H.; Stable and functionable mesoporous silica-coated gold nanorods as sensitive localized surface plasmon resonance (LSPR) nanosensors. Langmuir 2009, 25, 94419446. (43) Wang. G.; Chen. Z.; Chen. L.; Mesoporous silica-coated gold nanorods: towards sensitive colorimetric sensing of ascorbic acid via target-induced silver overcoating. Nanoscale 2011, 3, 1756-1759. (44) Yamamoto. S.; Matsuoka. O.; Fukada. I.; Ashida. Y.; Honda. T.; Yamamoto. N.; Using atomic force microscopy to image the surface of the powdered catalyst KMn8O16. J. Catal. 1996, 159, 401-409. (45) Malloy. A. P.; Donne. S. W.; Surface characterisation of chemically reduced electrolytic manganese dioxide. J. Colloid. Interf. Sci. 2008, 320, 210-218. (46) Juliena. C.; Massotb. M.; Baddour-Hadjeanc. R.; Frangerd. S.; Bachd. S.; Pereira-Ramos. J. P.; Raman spectra of birnessite manganese dioxides. Solid. State. Ionics. 2003, 159, 345-356. (47) Huang. N.; Qu. Z.; Dong. C.; Qin. Y.; Duan. X.; Superior performance of α@β-MnO2 for the toluene oxidation: active interface and oxygen vacancy. Appl. Catal. A-Gen. 2018, 560, 195205. (48) Dong. Y.; Li. K.; Jiang. P.; Wang. G.; Miao. H.; Zhang. J.; Zhang. C.; Simple hydrothermal preparation of α-, β-, and γ-MnO2 and phase sensitivity in catalytic ozonation. RSC Adv 2014, 4,


28

Page 29 of 31 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


39167-39173. (49) Julien. C. M.; Massot. M.; Poinsignon. C.; lattice vibrations of manganese oxides part I. periodic structures. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 2004, 60, 689-700. (50) Zhang. S.; Fan. Q.; Gao. H.; Huang. Y.; Liu. X.; Li. J.; Xu. X.; Wang. X.; Formation of Fe3O4@MnO2 ball-in-ball hollow spheres as a high performance catalyst with enhanced catalytic performances. J. Mater. Chem. A. 2016, 4, 1414-1422. (51) Zhang. S.; Gao. H.; Li. J.; Huang. Y.; Alsaedi. A.; Hayat. T.; Xu. X.; Wang. X.; Rice husks as a sustainable silica source for hierarchical flower-like metal silicate architectures assembled into ultrathin nanosheets for adsorption and catalysis. J. Hazard. Mater. 2017, 321, 92-102. (52) Chen. H.; Li. J.; Wu. X.; Wang. X.; Synthesis of alumina-modified cigarette soot carbon as an adsorbent for efficient arsenate removal. Ind. Eng. Chem. Res. 2014, 53, 16051-16060. (53) Liu. J.; Liang. H.; Li. M.; Luo. Z.; Zhang. J.; Guo. X.; Cai. K.; Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy. Biomaterials 2018, 157, 107-124. (54) Doane. T. L.; Burda. C.; The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chem. Soc. Rev. 2012, 41, 2885-2911. (55) Yang. X.; He. D.; He. X.; Wang. K.; Zou. Z.; Li. X.; Shi. H.; Luo. J.; Yang. X.; Glutathionemediated degradation of surface-capped MnO2 for drug release from mesoporous silica nanoparticles to cancer cells. Part & Par. Syst. Char. 2015, 32, 205-212. (56) Zhao. L.; Ge. X.; Zhao. H.; Shi. L.; Capobianco. J. A.; Jin. D.; Sun. L.; Double-sensitive drug release system based on MnO2 assembled upconversion nanoconstruct for double-model


29


Page 30 of 31

guided chemotherapy. ACS. Appl. Nano. Mater. 2018, 1, 1648-1656. (57) Gong. F.; Chen. J.; Han. X.; Zhao. J.; Wang. M.; Feng. L.; Li. Y.; Liu. Z.; Cheng. L.; Coreshell TaOx@MnO2 nanoparticles as a nano-radiosensitizer for effective cancer radiotherapy. J. Mater. Chem. B. 2018, 6, 2250-2257. (58) Tao. Y.; Zhu. L.; Zhao. Y.; Yi. X.; Zhu. L.; Ge. F.; Mou. X.; Chen. L.; Sun. L.; Yang. K.; Nano-graphene oxide-manganese dioxide nanocomposites for overcoming tumor hypoxia and enhancing cancer radioisotope therapy. Nanoscale 2018, 10, 5114-5123. (59) Ritger. P. L.; Peppas. N. A.; A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J. Control. Release. 1987, 5, 37-42. (60) Xu. S.; Shi. J.; Feng. D.; Yang. L.; Cao. S.; Hollow hierarchical hydroxyapatite/Au/ polyelectrolyte hybrid microparticles for multi-responsive drug delivery. J. Mater. Chem. B. 2014, 2, 6500-6507. (61) Omari. D. M.; Sallam. A.; Abd-Elbary. A.; El-Samaligy. M.; Lactic acid-induced modifications in films of eudragit RL and RS aqueous dispersions. Int. J. Pharm. 2004, 274, 8596.


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Graphic for Manuscript：

Mesoporous manganese dioxide coated gold nanorods with excellent photothermal transition efficiency, GSH-/pH-/NIR-responsive properties and degradability.


Mesoporous Manganese Dioxide Coated Gold Nanorods as a

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