Abstract
Osteoarthritis (OA) treatment mainly relies on developing new drugs or nanocarriers, while little attention is paid to building novel remedial mode and improving drug loading efficiency. This work reports an integrated nanosystem that not only realizes visual drug loading and release, but also achieves enhanced lubrication and effective joint inflammation therapy based on fluorinated graphene quantum dots (FGQDs). Oxygen introduction promotes FGQDs outstanding water-stability for months, and layered nano-sized structure further guarantees excellent lubricating properties in biomimetic synovial fluid. The special design of chemistry and structure endows FGQDs robust fluorescence in a wide range of pH conditions. Also, the excitation spectrum of FGQDs well overlaps the absorption spectrum of drugs, which further constructs a new concept of internal filtering system to visually monitor drug loading by naked eyes. More importantly, extraordinary long-term lubrication performance is reported, which is the first experimental demonstration of concentration-dependent mutations of coefficient of friction (COF). Cell incubation experiments indicate that drug-loaded FGQDs have good biocompatibility, tracking property of cellular uptake and drug release, which show efficient anti-inflammation potential for H2O2-induced chondrocyte degradation by up-regulated cartilage anabolic genes. This study establishes a promising OA treatment strategy that enables to monitor drug loading and release, to enhance long-time lubricating property, and to show effective anti-inflammatory potential for cartilage protection.
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References
Yan X, Yang B, Chen Y R, Song Y F, Ye J, Pan Y F, Zhou B N, Wang Y Q, Mao F B, Dong Y C, et al. Anti-friction MSCs delivery system improves the therapy for severe osteoarthritis. Adv Mater 33(52): 2104758 (2021)
Xie R, Yao H, Mao A S, Zhu Y, Qi D, Jia Y, Gao M, Chen Y, Wang L, Wang D A, et al. Biomimetic cartilage-lubricating polymers regenerate cartilage in rats with early osteoarthritis. Nat Biomed Eng 5(10): 1189–1201 (2021)
Lei Y T, Wang Y D, Shen J L, Cai Z W, Zhao C, Chen H, Luo X J, Hu N, Cui W G, Huang W. Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis. Sci Adv 8(5): eabl6449 (2022)
Rahimi M, Charmi G, Matyjaszewski K, Banquy X, Pietrasik J. Recent developments in natural and synthetic polymeric drug delivery systems used for the treatment of osteoarthritis. Acta Biomater 123: 31–50 (2021)
Bryk M, Chwastek J, Mlost J, Kostrzewa M, Starowicz K. Sodium monoiodoacetate dose-dependent changes in matrix metalloproteinases and inflammatory components as prognostic factors for the progression of osteoarthritis. Front Pharmacol 12: 643605 (2021)
Zhao B S, Li Y P, Wang Q N, Ren Y, Zheng Z L, Bai M H, Lv J C, Li K, Xu J Z, Li Z M, et al. Ultra-slippery, nonirritating, and anti-inflammatory hyaluronic acid-based coating to mitigate intubation injury. Chem Eng J 427: 130911 (2022)
Felson D T. Osteoarthritis: Virtual joint replacement as an outcome measure in OA. Nat Rev Rheumatol 8(4): 187–188 (2012)
Wan L, Wang Y, Tan X L, Sun Y L, Luo J, Zhang H Y. Biodegradable lubricating mesoporous silica nanoparticles for osteoarthritis therapy. Friction 10(1): 68–79 (2022)
Zhang W, Ouyang H W, Dass C R, Xu J K. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4: 15040 (2016)
Lin X J, Tsao C T, Kyomoto M, Zhang M Q. Injectable natural polymer hydrogels for treatment of knee osteoarthritis. Adv Healthc Mater 11(9): e2101479 (2022)
Feng W, Long P, Feng Y Y, Li Y. Two-dimensional fluorinated graphene: Synthesis, structures, properties and applications. Adv Sci 3(7): 1500413 (2016)
Kansara V, Shukla R, Flora S J S, Bahadur P, Tiwari S. Graphene quantum dots: Synthesis, optical properties and navigational applications against cancer. Mater Today Commun 31: 103359 (2022)
Wang Z D, Hu T T, Liang R Z, Wei M. Application of zero-dimensional nanomaterials in biosensing. Front Chem 8: 320 (2020)
Cardoso V F, Correia D M, Ribeiro C, Fernandes M M, Lanceros-Méndez S. Fluorinated polymers as smart materials for advanced biomedical applications. Polymers 10(2): 161 (2018)
Yu M N, Liu M M, Zhang D D, Fu S H. Lubricant-grafted omniphobic surfaces with anti-biofouling and drag-reduction performances constructed by reactive organic—inorganic hybrid microspheres. Chem Eng J 422: 130113 (2021)
Wang L, Gong P W, Li W, Luo T, Cao B Q. Mono-dispersed Ag/graphene nanocomposite as lubricant additive to reduce friction and wear. Tribol Int 146: 106228 (2020)
Tian R, Jia X H, Yang J, Li Y, Song H J. Large-scale, green, and high-efficiency exfoliation and noncovalent functionalization of fluorinated graphene by ionic liquid crystal. Chem Eng J 395: 125104 (2020)
Tang W W, Zhang Z, Li Y F. Applications of carbon quantum dots in lubricant additives: A review. J Mater Sci 56(21): 12061–12092 (2021)
He C, E S, Yan H H, Li X J. Structural engineering design of carbon dots for lubrication. Chinese Chem Lett 32(9): 2693–2714 (2021)
Chung S, Revia R A, Zhang M Q. Graphene quantum dots and their applications in bioimaging, biosensing, and therapy. Adv Mater 33(22): e1904362 (2021)
Gong P W, Zhao Q, Dai D J, Zhang S M, Tian Z Z, Sun L, Ren J S, Liu Z. Functionalized ultrasmall fluorinated graphene with high NIR absorbance for controlled delivery of mixed anticancer drugs. Chemistry 23(69): 17531–17541 (2017)
Gong P W, Wang J Q, Hou K M, Yang Z G, Wang Z F, Liu Z, Han X X, Yang S R. Small but strong: The influence of fluorine atoms on formation and performance of graphene quantum dots using a gradient F-sacrifice strategy. Carbon 112: 63–71 (2017)
Ettefaghi E, Rashidi A, Ghobadian B, Najafi G, Ghasemy E, Khoshtaghaza M H, Delavarizadeh S, Mazlan M. Bio-nano emulsion fuel based on graphene quantum dot nanoparticles for reducing energy consumption and pollutants emission. Energy 218: 119551 (2021)
Gong J, Zhang Z Y, Zeng Z P, Wang W J, Kong L X, Liu J Y, Chen P. Graphene quantum dots assisted exfoliation of atomically-thin 2D materials and as-formed 0D/2D van der Waals heterojunction for HER. Carbon 184: 554–561 (2021)
Song S H, Wang D D, Zhao K, Wu Y T, Zhang P, Liu J F, Yang G, Gong P W, Liu Z. Donor—acceptor structured photothermal COFs for enhanced starvation therapy. Chem Eng J 442: 135963 (2022)
Yousaf M, Huang H, Li P, Wang C, Yang Y L. Fluorine functionalized graphene quantum dots as inhibitor against hIAPP amyloid aggregation. ACS Chem Neurosci 8(6): 1368–1377 (2017)
Chua C K, Sofer Z, Šimek P, Jankovský O, Klímová K, Bakardjieva S, Hrdličková Kučková Š, Pumera M. Synthesis of strongly fluorescent graphene quantum dots by cage-opening buckminsterfullerene. ACS Nano 9(3): 2548–2555 (2015)
Yang L K, Li Y W, Wang L Y, Pei Y X, Wang Z Y, Zhang Y, Lin H, Li X. Exfoliated fluorographene quantum dots as outstanding passivants for improved flexible perovskite solar cells. ACS Appl Mater Inter 12(20): 22992–23001 (2020)
Gong P W, Wang Z F, Wang J Q, Wang H G, Li Z P, Fan Z J, Xu Y, Han X X, Yang S R. One-pot sonochemical preparation of fluorographene and selective tuning of its fluorine coverage. J Mater Chem 22(33): 16950–16956 (2012)
Mathkar A, Narayanan T N, Alemany L B, Cox P, Nguyen P, Gao G H, Chang P, Romero-Aburto R, Mani S A, Ajayan P M. Synthesis of fluorinated graphene oxide and its amphiphobic properties. Part Part Syst Char 30(3): 266–272 (2013)
Yan Y F, Sun T, Zhang H B, Ji X L, Sun Y L, Zhao X, Deng L F, Qi J, Cui W G, Santos H A, et al. Euryale Ferox seed-inspired superlubricated nanoparticles for treatment of osteoarthritis. Adv Funct Mater 29(4): 1807559 (2019)
Zhang J Y, Zhou R H, Tang D D, Hou X D, Wu P. Optically-active nanocrystals for inner filter effect-based fluorescence sensing: Achieving better spectral overlap. Trac-Trend Anal Chem 110: 183–190 (2019)
Peng J Y, Gong P W, Li S H, Kong F, Ge X X, Wang B, Guo L H, Liu Z, You J M. A smart bioresponsive nanosystem with dual-modal imaging for drug visual loading and targeted delivery. Chem Eng J 391: 123619 (2020)
Chen S, Yu Y L, Wang J H. Inner filter effect-based fluorescent sensing systems: A review. Anal Chim Acta 999: 13–26 (2018)
Lin M, Zou H Y, Yang T, Liu Z X, Liu H, Huang C Z. An inner filter effect based sensor of tetracycline hydrochloride as developed by loading photoluminescent carbon nanodots in the electrospun nanofibers. Nanoscale 8(5): 2999–3007 (2016)
Gong P W, Zhao K, Liu X C, Li C, Liu B, Hu L Y, Shen D Y, Wang D D, Liu Z. Fluorescent COFs with a highly conjugated structure for combined starvation and gas therapy. ACS Appl Mater Inter 14(41): 46201–46211 (2022)
Shin K R, Kim Y S, Kim G W, Ko Y G, Shin D H. Development of titanium oxide layer containing nanocrystalline zirconia particles with tetragonal structure: Structural and biological characteristics. Colloid Surface B 131: 47–53 (2015)
Wu W, Liu J X, Gong P W, Li Z H, Ke C, Qian Y, Luo H W, Xiao L S, Zhou F, Liu W M. Construction of core—shell nanoMOFs@microgel for aqueous lubrication and thermal-responsive drug release. Small 18(28): 2202510 (2022)
Kong S, Wang J B, Hu W J, Li J S. Effects of thickness and particle size on tribological properties of graphene as lubricant additive. Tribol Lett 68(4): 112 (2020)
Mou Z H, Yang Q B, Zhao B, Li X Q, Xu Y X, Gao T T, Zheng H, Zhou K, Xiao D. Scalable and sustainable synthesis of carbon dots from biomass as efficient friction modifiers for polyethylene glycol synthetic oil. ACS Sustain Chem Eng 9(44): 14997–15007 (2021)
Ren K X, Yu G M, Zhang Z X, Wu W C, Tian P, Chhattal M, Gong Z B, Li Y, Zhang J Y. Self-organized transfer film-induced ultralow friction of graphene/MoWS4 heterostructure nanocomposite. Appl Surf Sci 572: 151443 (2022)
Tang G B, Su F H, Xu X, Chu P K. 2D black phosphorus dotted with silver nanoparticles: An excellent lubricant additive for tribological applications. Chem Eng J 392: 123631 (2020)
Ji X L, Yan Y F, Sun T, Zhang Q, Wang Y X, Zhang M, Zhang H Y, Zhao X. Glucosamine sulphate-loaded distearoyl phosphocholine liposomes for osteoarthritis treatment: Combination of sustained drug release and improved lubrication. Biomater Sci 7(7): 2716–2728 (2019)
Chen H, Sun T, Yan Y F, Ji X L, Sun Y L, Zhao X, Qi J, Cui W G, Deng L F, Zhang H Y. Cartilage matrix-inspired biomimetic superlubricated nanospheres for treatment of osteoarthritis. Biomaterials 242: 119931 (2020)
Ahmed M R, Mehmood A, Bhatti F U R, Khan S N, Riazuddin S. Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage. Osteoarthr Cartilage 22(11): 1894–1901 (2014)
Zhang K, Yang J L, Sun Y L, Wang Y, Liang J, Luo J, Cui W G, Deng L F, Xu X Y, Wang B, et al. Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release. Friction 10(2): 232–246 (2022)
Acknowledgements
This research was supported by the National Natural Science Foundation of China (51905304, 52275202, and 21972153), China Post-doctoral Science Foundation (2022M712582), and Shandong Natural Science Foundation (ZR2022QE037).
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The authors have no competing interests to declare that are relevant to the content of this article. The author Weimin LIU is the Editorial Board Member of this journal.
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Peiwei GONG. He received his Ph.D. degree in 2015 from State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences (CAS), China. He performed his postdoctoral research at Northwestern Polytechnical University, China, since 2020. Currently, He is an associate professor at Qufu Normal University, China. He has authored or co-authored more than 60 journal papers. His research interests focus on biotribology, solid lubrication, and tribochemistry.
Changmin QI. She received her B.S. degree in 2022 from Qufu Normal University, China. She is currently a Ph.D. student in LICP, CAS, China. Her research interests are biotribology and supramolecular gel lubricants.
Dandan WANG. She received her M.S. degree in 2013 from Changzhou University, China, and then worked as a research assistant in State Key Laboratory of Solid Lubrication, LICP, CAS, China. Presently, she is a lecturer of Qufu Normal University, China. Her research interests are biotribology, lubricating oil, and additives.
Mianran CHAO. She received her Ph.D. degree in 2015 from State Key Laboratory of Solid Lubrication, LICP, CAS, China. She is currently a lecturer in Qufu Normal University, China. She has authored or co-authored more than 15 journal and conference papers. Her research interests are lubricant additives, antioxidants, kinetics, and mechanism of oxidation reactions.
Jianxi LIU. He obtained his Ph.D. degree from Karlsruhe Institute of Technology, Germany, in 2015. He performed his postdoctoral research at Northwestern University, USA, from 2016 to 2018. In 2018, he started his independent research career at Northwestern Polytechnical University, China. Currently, He is an associate professor in Northwestern Polytechnical University, China. His research interests focus on smart lubrication, multifunctional coatings, nanofabrication, and optical sensing.
Meirong CAI. She obtained her Ph.D. degree in 2012 at LICP, CAS, China. She is currently a full professor at State Key Laboratory of Solid Lubrication, LICP, CAS, China. She has authored or co-authored 80 journal papers, which have received more than 1,500 citations and have the high-index of 24. Her research interests are tribochemistry, ionic liquid lubricants, and supramolecular gel lubricants.
Weimin LIU. He received his Ph.D. degree in lubricating materials and tribology from LICP, CAS, China, in 1990. Subsequently, he joined State Key Laboratory of Solid Lubrication, LICP, CAS, China. From June 1993 to June 1994, he worked as a visiting scholar at The Pennsylvania State University, USA. In 2013, he was elected a member of CAS, China. Currently, he is a professor of LICP, CAS, China. To date, he has published more than 500 papers with citations of over 39,000. He holds more than 100 Chinese patents and 1 U.S. patent and won 2 National Awards for Technological Invention (second class) and 2 National Awards for Natural Sciences (second class). He serves as one of the three chief editors of Tribology International. Currently, his research interests mainly focus on space and aviation lubrication, high-performance lubricating materials, and tribochemistry.
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Gong, P., Qi, C., Wang, D. et al. Fluorinated graphene quantum dots with long-term lubrication for visual drug loading and joint inflammation therapy. Friction 11, 2204–2220 (2023). https://doi.org/10.1007/s40544-022-0714-6
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DOI: https://doi.org/10.1007/s40544-022-0714-6