原位產氫系統調控氧化壓力｜國立清華大學博碩士論文庫

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研究生：	萬瑋琳 Wan, Wei-Lin
論文名稱：	原位產氫系統調控氧化壓力 In Situ H2-Evolving Systems for Mitigating Oxidative Stress
指導教授：	宋信文 Sung, Hsing-Wen
口試委員:	葉晨聖 Yeh, Chen-Sheng 何佳安 Ho, Ja-an Annie 張燕 Chang, Yen 林滄城呂瑞梅蘇慕寰 Su, Muh-Hwan
學位類別：	博士 Doctor
系所名稱：	工學院 - 化學工程學系 Department of Chemical Engineering
論文出版年：	2018
畢業學年度：	107
語文別：	英文
論文頁數：	68
中文關鍵詞：	氫氣、活性氧化物質、光合作用、奈米反應器、上轉換奈米粒子、金奈米粒子、診療、鎂、骨關節炎
外文關鍵詞：	hydrogen gas, reactive oxygen species, photosynthesis, nanoreactor, upconversion nanoparticle, gold nanoparticle, theranostics, magnesium, osteoarthritis
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發炎反應在人類許多疾病中起著關鍵作用，這些疾病都涉及活性氧化物質的過量產生。氫氣是一種治療性醫療氣體，安全且無副作用。氫氣可以選擇性的清除具細胞毒性的活性氧化物質，而不影響其他活性氧化物質，保有其正常生理訊號調節，重建活性氧化物質的恆定。然而，透過傳統遞送氫氣的方式，氫氣的量可能不足以清除在發炎組織中過量產生的活性氧化物質。因此，透過局部遞送氫氣可以克服上述困難。在第一部分研究中，受自然界光合作用的啟發，光合奈米反應器鑲嵌有葉綠素a，包覆著L-抗壞血酸和金奈米粒子，光照下可以產生具有生物治療性的氫氣用以減輕局部發炎反應。以光合產氫的奈米反應器降低了巨噬細胞內活性氧化物質和促炎細胞因子的過量表現，降低小鼠發炎組織的氧化壓力。為了增加治療深度並降低生物組織中的光毒性，在第二部份研究中，結合上轉換奈米粒子製備出具有偵測及降低氧化壓力的奈米平台。通過具有活性氧化物質響應的化合物將上轉換奈米粒子與金奈米粒子結合形成奈米複合物，將其包覆於鑲嵌有葉綠素a的奈米平台中。奈米平台作為光捕獲之天線，集診斷、治療和評估治療效果，可同時成像和原位治療。然而，為了治療如骨關節炎的慢性疾病，需要一種能夠在患部中連續提供高治療濃度的氫氣系統，在第三部分研究中提出的遞送系統為包覆有鎂粉的聚乳酸乙醇酸微粒。在小鼠骨關節炎模型中以肌肉注射方式注射包覆有鎂粉的聚乳酸乙醇酸微粒於患部附近，其可以透過在體液中鎂的鈍化/活化循環而連續地釋放氫氣，結果顯示，包覆有鎂粉的聚乳酸乙醇酸微粒可有效緩解組織發炎並防止軟骨降解，減緩骨關節炎的進程。這些分析結果證明了以上三種氫氣遞送系統提供多功能治療診斷平台用以治療疾病的可行性。

Inﬂammation has a critical role in the onset of many human diseases, all of which involve the disturbance of reactive oxygen species (ROS) homeostasis. Hydrogen (H2) is a therapeutic medical gas, regarding to be safe and no side-effects. H2 can selectively scavenge highly cytotoxic ROS while preserve other essential ROS for normal signaling regulation, reestablishing ROS homeostasis. However, the amount of H2 that is absorbed by the body through the traditional approaches may not suffice to scavenge the ROS that is overproduced in inflamed tissues. Thus, local delivery of H2 gas may overcome the above difficulty. Inspired by natural photosynthesis, the photo-driven nanoreactor (NR) that comprises chlorophyll a (Chla), L-ascorbic acid, and gold nanoparticles (AuNPs) that are encapsulated in a liposomal (Lip) system that can produce H2 gas with therapeutic concentration in situ upon photon absorption to mitigate inflammatory responses is proposed in the first study. This photo-driven NR system reduces the degrees of overproduction of ROS and pro-inflammatory cytokines both in vitro in RAW264.7 cells and in vivo in mice with paw inflammation that is induced by lipopolysaccharide. Experimental results indicate that the Lip NR system that can photosynthesize H2 gas has great potential for mitigating oxidative stress in tissue inflammation. To increase the therapeutic depth and minimize the phototoxicity in biological tissues, an NIR-to-vis-driven H2-evolving Lip nanoplatform (Lip NP) is proposed in the second study. An upconversion nanoparticle that is conjugated with AuNPs via an ROS-responsive linker, which is encapsulated inside the liposomal system in whose lipid bilayer is embedded Chla. Functioning as light-harvesting antennas, Lip NP integrates diagnosis, therapy, and the monitoring of therapeutic effects, for simultaneous imaging and therapy in situ. To treat chronic diseases such as osteoarthritis (OA), a system that can continuously provide a high therapeutic concentration of gaseous H2 in diseased tissues is needed. The delivery system proposed in the third study comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids. The proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes. These analytical results demonstrate the feasibility of using H2-generating systems to provide the multifunctional theranostic platform in the treatment of inflamed tissue.

中文摘要 ------------------------------------I
Abstract ----------------------------------II
Table of Contents -------------------------IV
List of Figures ---------------------------IX
List of Tables ---------------------------XII

Chapter 1. Introduction -------------------------------------------1

Chapter 2. In Situ Nanoreactor for Photosynthesizing H2 Gas to Mitigate Oxidative Stress in Tissue Inflammation ------------------5

2.1. Introduction -------------------------------------------------6
2.2. Results and discussion ---------------------------------------8
2.2.1. Preparation and characterization of test Lips --------------8
2.2.2. Cytotoxicity of the Lip NRs -------------------------------12
2.2.3. Inhibition of ROS in LPS-induced RAW264.7 cells -----------13
2.2.4. Inhibition of pro-inflammatory cytokines in LPS-stimulated RAW264.7 cells ---------------------------------------------------15
2.2.5. Animal model ----------------------------------------------16
2.2.6. In vivo efficacy study ------------------------------------17
2.3. Conclusions -------------------------------------------------18
2.4. Materials and methods ---------------------------------------19
2.4.1. Materials--------------------------------------------------19
2.4.2. Preparation of test Lips ----------------------------------19
2.4.3. Characterization of test Lips -----------------------------19
2.4.4. SAXS measurements -----------------------------------------20
2.4.5. Ultrasound imaging ----------------------------------------20
2.4.6. Measurements of cumulated H2 concentrations ---------------20
2.4.7. Hydroxyl radical scavenging capacity ----------------------21
2.4.8. Cell viability --------------------------------------------21
2.4.9. Measurement and visualization of cellular ROS -------------21
2.4.10.Determination of cytokine production ----------------------21
2.4.11.Animal study ----------------------------------------------22
2.4.12.Statistical analysis --------------------------------------23

Chapter 3.    An NIR-to-Vis-Driven H2 Evolution Nanoplatform that Can Detect Concentration of ROS In Situ and Restore Their Homeostasis ------------------------------------------------------24

3.1. Introduction ------------------------------------------------25
3.2. Results and discussion --------------------------------------27
3.2.1. Preparation and characterization of Lip NP ----------------27
3.2.2. FRET effect -----------------------------------------------31
3.2.3. Kinetics of nanocomplex to H2O2 ---------------------------32
3.2.4. Sensitivity of nanocomplex to H2O2 ------------------------32
3.2.5. Evolution of gaseous H2------------------------------------34
3.2.6. Cytotoxicity of the Lip NPs -------------------------------34
3.2.7. Anti-inflammation in LPS-stimulated macrophages -----------35
3.2.8. Light propagation in porcine skin tissues -----------------37
3.2.9. Lip NP for H2O2 detection and H2 evolution in porcine skin tissues ----------------------------------------------------------37
3.3. Conclusions -------------------------------------------------38
3.4. Materials and methods ---------------------------------------38
3.4.1. Materials -------------------------------------------------38
3.4.2. Syntheses of OA-UCNPs and Cit-UCNPs -----------------------39
3.4.3. Synthesis of ROS-responsive TK-based linker ---------------39
3.4.4. Preparation and characterization of Cit-UCNP-TK-AuNPs and Lip NP----------------------------------------------------------------39
3.4.5. Sensitivity of Cit-UCNP-TK-AuNPs to H2O2 ------------------40
3.4.6. Evolution of gaseous H2 -----------------------------------41
3.4.7. Cytotoxicity of Lip NPs -----------------------------------41
3.4.8. Levels of cellular ROS ------------------------------------41
3.4.9. Evaluation of cellular pro-Inflammatory cytokines ---------42
3.4.10.Determination of NIR penetration depth --------------------42
3.4.11.Statistical analysis --------------------------------------43

Chapter 4. In Situ Depot for Continuous Evolution of Gaseous H2 Mediated by Magnesium Passivation/Activation Cycle for Treating Osteoarthritis ---------------------------------------------------44

4.1. Introduction ------------------------------------------------45
4.2. Results and discussion --------------------------------------47
4.2.1. Preparation and characterization of Mg@PLGA MPs -----------47
4.2.2. Cytotoxicity of free Mg and Mg@PLGA MPs -------------------48
4.2.3. Evolution of gaseous H2------------------------------------50
4.2.4. Inhibition of cellular ROS and pro-inflammatory cytokines in LPS-stimulated RAW264.7 cells ------------------------------------50
4.2.5. Animal model ----------------------------------------------52
4.2.6. In vivo efficacy of Mg@PLGA MPs in tissue inflammation ----53
4.2.7. In vivo efficacy of Mg@PLGA MPs in cartilage protection ---54
4.3. Conclusions -------------------------------------------------56
4.4. Materials and methods----------------------------------------56
4.4.1. Materials -------------------------------------------------56
4.4.2. Preparation and characterization of Mg@PLGA MPs -----------57
4.4.3. Measurements of concentrations of evolved gaseous H2 ------57
4.4.4. Assessment of cytotoxicity --------------------------------57
4.4.5. Analysis of cellular ROS levels ---------------------------58
4.4.6. Evaluation of cytokine production -------------------------58
4.4.7. Animal study ----------------------------------------------59
4.4.8. Measurement of tissue ROS levels --------------------------60
4.4.9. Analysis of biochemical markers ---------------------------60
4.4.10.Histological examinations ---------------------------------60
4.4.11.Statistical analysis --------------------------------------60

Chapter 5. References --------------------------------------------61

List of Figures
Figure 2-1. Composition/structure of photo-driven NR and mechanisms of its photosynthesis of H2 gas in situ to reduce overproduction of oxidative stress in LPS-induced inflamed paw created in a mouse model. ------------------------------------------------------------8
Figure 2-2. Size distribution of as-prepared NR. ------------------9
Figure 2-3. (a) SAXS profiles and (b) electron density distributions of plain Lips and NR. --------------------------------------------10
Figure 2-4. (a) Fluorescence images of Chla embedded in Lip membrane of NR. (b) TEM images of AuNPs encapsulated in NR. (c) Spectral changes of AA encapsulated in NR following various periods of laser irradiation. (d) Bright field images of H2 bubble generation in an NR following laser irradiation. (e) Ultrasound images of H2 bubble generation in BS and NR following laser irradiation. (f) Cumulative H2 concentrations generated in BS and NR following laser irradiation. (g) Hydroxyl radical scavenging activities of BS and NR without/with laser irradiation. *P < 0.05. -----------------------11
Figure 2-5. (a) Cell viability of RAW264.7 cells co-cultured with various concentrations of NR without/with laser irradiation. (b) Time-dependent effects of LPS-induced ROS production in RAW264.7 cells. -----------------------------------------------------------13
Figure 2-6. DCF intensities of intracellular ROS levels in LPS-stimulated RAW264.7 cells following treatment with various concentrations of NR without/with laser irradiation. Concentrations of Chla/AA/AuNPs that were used in BS were equivalent to those encapsulated in NR. *P < 0.05; n.s.: not significant. ------------14
Figure 2-7. (a) DCF intensities and (b) CLSM images of LPS-induced ROS production in RAW264.7 cells following various treatments. (c) Levels of inflammatory cytokines IL-6 and IL-1β and (d) corresponding fluorescence images in RAW264.7 cells following various treatments. *P < 0.05; n.s.: not significant. ------------16
Figure 2-8. IVIS images and corresponding L-012 luminescence intensities of ROS in LPS-induced inflamed paws following treatment with various volumes of NR (2.5 mg/mL) under laser irradiation. --17
Figure 2-9. (a) IVIS images and (b) corresponding L-012 luminescence intensities of ROS in LPS-induced inflamed paws following treatment with BS and NR without/with laser irradiation. (c) Levels of inflammatory cytokines IL-6 and IL-1β and (d) corresponding fluorescence images and (e) H&E staining images of inflamed paws following various treatments without/with laser irradiation. *P < 0.05. ------------------------------------------------------------18
Figure 3-1. Composition/structure of an as-proposed Lip NP, whose aqueous core encapsulates Cit-UCNP-TK-AuNPs nanocomplex and in whose lipid membrane is embedded Chla. NIR laser penetrates biological tissue and is converted to green and red UCL by Cit-UCNP in nanocomplex. Green UCL is used to measure local ROS concentration for FRET imaging, and red UCL induces photosynthesis of gaseous H2 to scavenge excess ROS. ------------------------------------------28
Figure 3-2. (A) TEM images of OA-UCNPs and Cit-UCNPs, and their corresponding emission images under NIR laser irradiation. (B) FT-IR spectra of OA-UCNPs and Cit-UCNPs. (C) 1H NMR spectrum of TK-based linker. (D) TGA thermograms of Cit-UCNPs and lipoic acid-capped AuNPs. (E) Zeta potentials of Cit-UCNPs, AuNPs, Cit-UCNP-TK, and nanocomplex. (F) STEM images and elemental composition of nanocomplex. (G) STEM images and (H) CLSM image of Lip NPs. Owing to limited optical resolution in CLSM, Lip NPs with diameters (1−3 m) were observed. ---------------------------------------------------31
Figure 3-3. (A) Fluorescence spectrum of Cit-UCNPs irradiated at 980 nm and UV/vis absorbance of AuNPs. Fluorescence excitation spectra of nanocomplexes following (B) incubation with 50 M H2O2 for various periods and (C) incubation with various concentrations of H2O2 for 30 min. (D) Linear correlation curve of green UCL (F/F0) intensity against concentration of H2O2. (E) Cumulative amount of gaseous H2 generated from BS or Lip NPs under NIR laser irradiation. (F) Cell viability of RAW264.7 cells incubated with various concentrations of Lip NPs. (G) DCF intensities of intracellular ROS levels in LPS-stimulated RAW264.7 cells following treatment with various concentrations of Lip NP−NIR or Lip NP+NIR. n.s.: not significant; *P < 0.05. ------------------------------------------33
Figure 3-4. (A) CLSM images of cellular ROS, IL-1 and IL-6 in LPS-stimulated RAW264.7 cells and (B) their corresponding intensities after various treatments. (C) Concentrations of remaining H2O2 following various treatments, estimated from linear correlation curve of green UCL (F/F0) intensity against concentration of H2O2. (D) Fluorescence images and intensities of tissue autofluorescence and NIR light propagation in porcine skin tissue injected with Cit-UCNPs. (E) Fluorescence images and intensities of NIR light propagation in porcine skin tissues injected with Lip NPs in absence/presence of H2O2 and their H2 evolution profiles. *P < 0.05. ------------------------------------------------------------------36
Figure 4-1. Composition/structure of as-proposed Mg@PLGA MPs and mechanism of their evolution of H2 gas in situ, suppressing tissue inflammation and preventing degradation of cartilage in mice with OA. --------------------------------------------------------------47
Figure 4-2. (a) SEM images of Mg@PLGA MPs fabricated with various water-to-oil volumetric ratios and (b) their effects on pH of culture-medium when co-cultured with RAW264.7 cells. (c) Bright field and (d) SEM images of Mg@PLGA MPs before and after solvent evaporation, respectively. (e) Changes in pH of culture-medium and cell viability for RAW264.7 cells that were incubated with free Mg or Mg@PLGA MPs. *P < 0.05. ---------------------------------------49
Figure 4-3. (a) Bright field images of H2 bubbles evolved from free Mg or Mg@PLGA MPs in DI water or PBS. (b) Profiles of gaseous H2 evolved from free Mg or Mg@PLGA MPs in PBS. (c) CLSM images of cellular ROS, IL-1β, and TNF- and (d) their corresponding intensities in LPS-stimulated RAW264.7 cells following various treatments. *P < 0.05; n.s.: not significant. --------------------51
Figure 4-4. (a) CLSM images of cellular IL-6 and (b) their corresponding intensities in LPS-stimulated RAW264.7 cells following various treatments. *P < 0.05; n.s.: not significant. ------------52
Figure 4-5. (a) IVIS images and corresponding L-012 intensities of ROS and (b) levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF- in MIA-stimulated knee joints following various treatments and (c) photomicrographs of their synovial tissue sections stained by H&E or TUNEL. *P < 0.05; n.s.: not significant. --------------54
Figure 4-6. (a) Levels of MMP-9 and MMP-13 in MIA-stimulated knee joints following various treatments and (b) photomicrographs of their cartilage sections stained by H&E, safranin O, collagen type II, or TUNEL. *P < 0.05; n.s.: not significant. ------------------56
List of Tables
Table 4-1. Loading efficiency and loading content of Mg powder in PLGA MPs fabricated with various water-to-oil volumetric ratios (n = 6). --------------------------------------------------------------48

                                

[1] D. Trachootham, J. Alexandre, P. Huang, Nat. Rev. Drug Discov. 2009, 8, 579.
[2] T. Finkel, J. Cell Biol. 2011, 194, 7.
[3] M. Nita, A.Grzybowski, Oxid. Med. Cell. Longev. 2016, 2016, 3164734.
[4] A. P. West, I. E. Brodsky, C. Rahner, D. K. Woo, H. Erdjument-Bromage, P. Tempst, M. C. Walsh, Y. Choi, G. S. Shadel, S. Ghosh, Nature 2011, 472, 476.
[5] B. Kalyanaraman, Redox Biol. 2013, 1, 244.
[6] P. D. Ray, B. W. Huang, Y. Tsuji, Cell. Signal. 2012, 24, 981.
[7] S. Di Meo, T. T. Reed, P. Venditti, V. M. Victor, Oxid. Med. Cell. Longev. 2016, 2016, 1245049.
[8] M. Hultqvist, L. M. Olsson, K. A. Gelderman, R. Holmdahl, Trends Immunol. 2009, 30, 201.
[9] Y. Yang, A. V. Bazhin, J. Werner, S. Karakhanova, Int. Rev. Immunol. 2013, 23, 249.
[10]H. Dumond, N. Presle, P. Pottie, S. Pacquelet, B. Terlain, P. Netter, A. Gepstein, E. Livne, J. Y. Jouzeau, Osteoarthritis Cartilage 2004, 12, 284.
[11]P. Lepetsos, A. G. Papavassiliou, Biochim. Biophys. Acta 2016, 1862, 576.
[12]J. Bondeson, A. B. Blom, S. Wainwright, C. Hughes, B. Caterson, W. B. van den Berg, Arthritis Rheum. 2010, 62, 647.
[13]A. Courties, O. Gualillo, F. Berenbaum, J. Sellam, Osteoarthritis Cartilage, 2015, 23, 1955.
[14]C. Liu, R. Kurokawa, M. Fujino, S. Hirano, B. Sato, X. K. Li, Sci. Rep. 2014, 4, 5485.
[15]I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K. Katsura, Y. Katayama, S. Asoh, S. Ohta, Nat. Med. 2007, 13, 688.
[16]M. Shen, H. Zhang, C. Yu, F. Wang, X. Sun, Med. Gas Res. 2014, 4, 17.
[17]M. Ichihara, S. Sobue, M. Ito, M. Ito, M. Hirayama, K. Ohno, Med. Gas Res. 2015, 5, 12.
[18]S. Zhao, Y. Yang, W. Liu, Z. Xuan, S. Wu, S. Yu, K. Mei, Y. Huang, P. Zhang, J. Cai, J. Ni, Y. Zhao, J. Cell. Mol. Med. 2014, 18, 938.
[19]S. Ohta, Pharmacol. Ther. 2014, 144, 1.
[20]Y. Wang, H. Suzuki, J. Xie, O. Tomita, D. J. Martin, M. Higashi, D. Kong, R. Abe, J. Tang, Chem. Rev. 2018, 118, 5201.
[21]B. Zheng, R. P. Sabatini, W. F. Fu, M. S. Eum, W. W. Brennessel, L. Wang, D. W. McCamant, R. Eisenberg, Proc. Natl. Acad. Sci. U. S. A. 2015, 112, E3987.
[22]D. Eguchi, M. Sakamoto, T. Teranishi, Chem. Sci. 2017, 9, 261.
[23]L. Liang, Y. Lu, R. Zhang, A. Care, T. A. Ortega, S. M. Deyev, Y. Qian, A. V. Zvyagin, Acta Biomater. 2017, 51, 461.
[24]W. Stopyra, J. Kurzac, K. Gruber, T. Kurzynowski, E. Chlebus, Proc. SPIE Int. Soc. Opt. Eng. 2016, 10159, 101590R-1.
[25]Y. Zhang, X. Zhan, J. Xiong, S. Peng, W. Huang, R. Joshi, Y. Cai, Y. Liu, R. Li, K. Yuan, N. Zhou, W. Min, Sci. Rep. 2018, 8, 8720.
[26]J. Peng, W. Xu, C. L. Teoh, S. Han, B. Kim, A. Samanta, J. C. Er, L. Wang, L. Yuan, X. Liu, Y. T. Chang, J. Am. Chem. Soc. 2015, 137, 2336.
[27]M. Wu, X. Wang, K. Wang, Z. Guo, Chem. Commun. 2016, 52, 8377.
[28]L. Mao, L. Shen, J. Chen, X. Zhang, M. Kwak, Y. Wu, R. Fan, L. Zhang, J. Pei, G. Yuan, C. Song, J. Ge, W. Ding, Sci. Rep. 2017, 7, 46343.
[29]R. Ambat, N. N. Aung, W. Zhou, J. Appl. Electrochem. 2014, 44, 411.
[30]Y. K. Kim, K. B. Lee, S. Y. Kim, K. Bode, Y. S. Jang, T. Y. Kwon, M. H. Jeon, M. H. Lee, Sci. Technol. Adv. Mater. 2018, 19, 324.
[31]M. Sheikhpour, L. Barani, A. Kasaeian, J. Control. Release 2017, 253, 97.
[32]X. Li, X. Jiang, Adv. Drug Deliv. Rev. 2018, 128, 101.
[33]C. Chen, J. Geng, F. Pu, X. Yang, J. Ren, X. Qu, Angew. Chem. Int. Ed. 2011, 50, 882.
[34]K. Liang, G. Such, A. Johnston, Z. Zhu, H. Ejima, J. Richardson, J. Cui, F. Caruso, Adv. Mater. 2014, 26, 1901.
[35]D. Schmaljohann, Adv. Drug Delivery Rev. 2006, 58, 1655.
[36]H. L. Pu, W. L. Chiang, B. Maiti, Z. X. Liao, Y. C. Ho, M. S. Shim, E. Y. Chuang, Y. Xia, H. W. Sung, ACS Nano 2014, 8, 1213.
[37]Y. S. Bae, J. H. Lee, S. H. Choi, S. Kim, F. Almazan, J. L. Witztum, Y. I. Miller, Circ. Res. 2009, 104, 210.
[38]T. Kurioka, T. Matsunobu, Y. Satoh, K. Niwa, A. Shiotani, Neurosci. Res. 2014, 89, 69.
[39]S. X. Guo, Q. Fang, C. G. You, Y. Y. Jin, X. G. Wang, X. L. Hu, C. M. Han, J. Transl. Med. 2015, 13, 183.
[40]A. Shimouchi, K. Nose, T. Mizukami, D. C. Che, M. Shirai, Adv. Exp. Med. Biol. 2013, 789, 315.
[41]S. Berardi, S. Drouet, L. Francàs, C. Gimbert-Suriñach, M. Guttentag, C. Richmond, T. Stoll, A. Llobet, Chem. Soc. Rev. 2014, 43, 7501.
[42]S. T. Jones, Z. Walsh-Korb, S. J. Barrow, S. L. Henderson, J. del Barrio, O. A. Scherman, ACS Nano 2016, 10, 3158.
[43]P. Y. Bolinger, D. Stamou, H. Vogel, J. Am. Chem. Soc. 2004, 126, 8594.
[44]L. Nováková, P. Solich, D. Solichová, Trends Analyt. Chem. 2008, 10, 942.
[45]Q. Zhang, K. Zhao, Q. Shen, Y. Han, Y. Gu, X. Li, D. Zhao, Y. Liu, C. Wang, X. Zhang, X. Su, J. Liu, W. Ge, R. L. Levine, N. Li, X. Cao, Nature 2015, 525, 389.
[46]Y. Takemura, M. Satoh, K. Satoh, H. Hamada, Y. Sekido, S. Kubota, Biochem. Biophys. Res. Commun. 2010, 394, 249.
[47]E. Wang, M. Wink, PeerJ 2016, 4, e1879.
[48]P. Wang, X. Wang, L. Wang, X. Hou, W. Liu, C. Chen, Sci. Technol. Adv. Mater. 2015, 16, 034610.
[49]H. Y. Ahn, K. E. Fairfull-Smith, B. J. Morrow, V. Lussini, B. Kim, M. V. Bondar, S. E. Bottle, K. D. Belfield, J. Am. Chem. Soc. 2012, 134, 4721.
[50]C. J. Su, S. S. Wu, U. Jeng, M. T. Lee, A. C. Su, K. F. Liao, W. Y. Lin, Y. S. Huang, C. Y. Chen, Biochim. Biophys. Acta. 2013, 1828, 528.
[51]A. W. Gardner, P. S. Montgomery, Y. D. Zhao, F. Silva-Palacios, Z. Ungvari, A. Csiszar, W. E. Sonntag, J. Vasc. Surg. 2017, 65, 1762.
[52]C. Tapeinos, A. Pandit, Adv. Mater. 2016, 28, 5553.
[53]G. Saravanakumar, J. Kim, W. J. Kim, Adv. Sci. 2017, 4, 1600124.
[54]E. Albers, V. S. Okreglak, C. J. Chang, J. Am. Chem. Soc. 2006, 128, 9640.
[55]K. M. Kang, Y. N. Kang, I. B. Choi, Y. Gu, T. Kawamura, Y. Toyoda, A. Nakao, Med. Gas Res. 2011, 1, 11.
[56]Y. He, B. Zhang, Y. Chen, Q. Jin, J. Wu, F. Yan, H. Zheng, ACS Appl. Mater. Interfaces 2017, 9, 21190.
[57]L. Huang, Med. Gas Res. 2016, 6, 219.
[58]W. L. Wan, Y. J. Lin, H. L. Chen, C. C. Huang, P. C. Shih, Y. R. Bow, W. T. Chia, H. W. Sung, J. Am. Chem. Soc. 2017, 139, 12923.
[59]T. Yang, Z. Jin, Z. Wang, P. Zhao, B. Zhao, M. Fan, L. Chen, T. Wang, B. L. Sub, Q. Hea, Applied Materials Today 2018, 11, 136.
[60]S. Han, B. W. Hwang, E. Y. Jeon, D. Jung, G. H. Lee, D. H. Keum, K. S. Kim, S. H. Yun, H. J. Cha, S. K. Hahn, ACS Nano 2017, 11, 9979.
[61]Z. Li, T. Liang, S. Lv, Q. Zhuang, Z. Liu, J. Am. Chem. Soc. 2015, 137, 11179.
[62]S. Wu, N. Duan, Z. Shi, C. Fang, Z. Wang, Talanta 2014, 128, 327.
[63]J. Tang, B. Kong, H. Wu, M. Xu, Y. Wang, Y. Wang, D. Zhao, G. Zheng, Adv. Mater. 2013, 25, 6569.
[64]A. M. Speers, G. Reguera, Appl. Environ. Microbiol. 2012, 78, 437.
[65]Q. Zou, K. Liu, M. Abbas, X. Yan, Adv. Mater. 2016, 28, 1031.
[66]H. X. Mai, Y. W. Zhang, R. Si, Z. G. Yan, L. D. Sun, L. P. You, C. H. Yan, J. Am. Chem. Soc. 2006, 128, 6426.
[67]A. Dong, X. Ye, J. Chen, Y. Kang, T. Gordon, J. M. Kikkawa, C. B. Murray, J. Am. Chem. Soc. 2011, 133, 998.
[68]M. S. Shim, Y. Xia, Angew. Chem. Int. Ed. 2013, 52, 6926.
[69]B. Dong, X. Song, X. Kong, C. Wang, Y. Tang, Y. Liu, W. Lin, Adv. Mater. 2016, 28, 8755.
[70]R. Weinstain, E. N. Savariar, C. N. Felsen, R. Y. Tsien, J. Am. Chem. Soc. 2014, 136, 874.
[71]S. Lee, A. Stubelius, N. Hamelmann, V. Tran, A. Almutairi, ACS Appl. Mater. Interfaces., DOI: 10.1021/acsami.8b08254.
[72]N. Su, Q. Wu, Y. Liu, J. Cai, W. Shen, K. Xia, J. Cui, J. Agric. Food Chem. 2014, 62, 6454.
[73]Q. Li, Y. Wen, X. You, F. Zhang, V. Shah, X. Chen, D. Tong, X. Wei, L. Yin, J. Wu, X. Xu, J. Mater. Chem. B 2016, 4, 4675.
[74]J. Li, C. Guo, F. Feng, A. Fan, Y. Dai, N. Li, D. Zhao, X. Chen, Y. Lu, Sci. Rep. 2016, 6, 38787.
[75]N. Davidovich, B. C. DiPaolo, G. G. Lawrence, P. Chhour, N. Yehya, S. S. Margulies, Am. J. Respir. Cell Mol. Biol. 2013, 49, 156.
[76]F. Berenbaum, Osteoarthritis Cartilage 2013, 21, 16.
[77]F. J. Blanco, A. M. Valdes, I. Rego-Pérez, Nat. Rev. Rheumatol. 2018, 14, 327.
[78]P. G. Mitchell, H. A. Magna, L. M. Reeves, L. L. Lopresti-Morrow, S. A. Yocum, P. J. Rosner, K. F. Geoghegan, J. E. Hambor, J. Clin. Invest. 1996, 97, 761.
[79]N. Gerwin, C. Hops, A. Lucke, Adv. Drug Deliv. Rev. 2006, 58, 226–242.
[80]T. Hanaoka, N. Kamimura, T. Yokota, S. Takai, S. Ohta, Med. Gas Res. 2011, 1, 18.
[81]Y. Xin, T. Hu, P. Chu, Acta Biomater. 2011, 7, 1452.
[82]C. Chen, E. Karshalev, J. Guan, J. Wang, Small 2018, 14, e1704252.
[83]F. Mou, C. Chen, H. Ma, Y. Yin, Q. Wu, J. Guan, Angew. Chem. Int. Ed. 2013, 52, 7208.
[84]F. Witte, H. Ulrich, M. Rudert, E. Willbold, J. Biomed. Mater. Res. A 2007, 81, 748.
[85]Z. Zhen, X. Liu, T. Huang, T. Xi, Y. Zheng, Mater. Sci. Eng. C Mater. Biol. Appl. 2015, 46, 202.
[86]D. Zhao, F. Witte, F. Lu, J. Wang, J. Li, L. Qin, Biomaterials 2017, 112, 287.
[87]S. C. Cifuentes, R. Gavilán, M. Lieblich, R. Benavente, J. L. González-Carrasco, Acta Biomater. 2016, 32, 348.
[88]M. M. Pakulska, I. Elliott Donaghue, J. M. Obermeyer, A. Tuladhar, C. K. McLaughlin, T. N. Shendruk, M. S. Shoichet, Sci. Adv. 2016, 2, e1600519.
[89]L. Jin, J. Wu, G. Yuan, T. Chen, PLoS One 2018, 13, e0193276.
[90]J. Li, P. Angsantikul, W. Liu, B. E.-F. de Ávila, S. Thamphiwatana, M. Xu, E. Sandraz, X. Wang, J. Delezuk, W. Gao, L. F. Zhang, J. Wang, Angew. Chem. Int. Ed. 2017, 56, 2156.
[91]L. Yu, P. Hu, Y. Chen, Adv. Mater., DOI: 10.1002/adma.201801964.
[92]R. X. Zhang, K. Ren, R. Dubner, Osteoarthritis Cartilage 2013, 21, 1308.
[93]A. Sarmanova, M. Hall, J. Moses, M. Doherty, W. Zhang, Osteoarthritis Cartilage 2016, 24, 1376.
[94]P. Maudens, C. A. Seemayer, C. Thauvin, C. Gabay, O. Jordan, E. Allémann, Small 2018, 14, 1703108.
[95]S. E. Bove, S. L. Calcaterra, R. M. Brooker, C. M. Huber, R. E. Guzman, P. L. Juneau, D. J. Schrier, K. S. Kilgore, Osteoarthritis Cartilage 2003, 11, 821.
[96]M. F. Chung, W. T. Chia, W. L. Y. J. Wan, Lin, H. W. Sung, J. Am. Chem. Soc. 2015, 137, 12462.
[97]G. X. Ni, Z. Li, Y. Z. Zhou, Osteoarthritis Cartilage 2014, 22, 896.
[98]A. M. Valdes, I. Meulenbelt, E. Chassaing, N. K. Arden, S. Bierma-Zeinstra, D. Hart, A. Hofman, M. Karsdal, M. Kloppenburg, H. M. Kroon, E. P. Slagboom, T. D. Spector, A. G. Uitterlinden, J. B. van Meurs, A. C. Bay-Jensen, Osteoarthritis Cartilage 2014, 22, 683.

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