Research Progress of Nanomaterial Targeted Drug Delivery in Osteoarthritis Treatment
Zhang Yingyu1, Zhao Linlin1,2, Li Liangxiao3, Liu Yingying1,3*, Liu Yajun1,4*
1(Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117,China) 2(School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China) 3(Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China) 4(Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing Research Institute of Traumatology and Orthopedics, Beijing 100035, China)
Abstract：Osteoarthritis is a chronic, highly prevalent degenerative disease. Delivering drugs to the joints presents challenges, as free drugs injected into the joints are prone to degradation and rapid clearance through the lymphatic and blood systems. Nano-targeted drug delivery systems, designed with specific assembly and appearance modifications, offer significant advantages. They can increase the drug concentration at the arthritic site, improve efficacy, reduce toxicity, therefore, have been extensively studied for uses in osteoarthritis treatment. This review introduced current nano-drug delivery strategies that featured active targeting in treating osteoarthritis, summarized research work on nano-drug delivery systems enhanced by biotargeting ligands and biomimetic biofilms, highlighting their advantages and limitations. In addition, we discussed the potential future developments of nano-drug delivery systems, aiming to provide references and constructive suggestions for improving the past active targeting and modification strategies of nanomaterials.
张颖煜, 赵琳琳, 李良骁, 刘营营, 刘亚军. 纳米材料靶向药物递送系统在骨关节炎治疗中的研究进展[J]. 中国生物医学工程学报, 2024, 43(3): 369-376.
Zhang Yingyu, Zhao Linlin, Li Liangxiao, Liu Yingying, Liu Yajun. Research Progress of Nanomaterial Targeted Drug Delivery in Osteoarthritis Treatment. Chinese Journal of Biomedical Engineering, 2024, 43(3): 369-376.
[1] Yun TG, Chen J, Meng ZL, et al. Research progress on osteoarthritis treatment mechanisms [J]. Biomed Pharmacother, 2017, 93: 1246-1252. [2] Knights AJ, Redding SJ, Maerz T. Inflammation in osteoarthritis: the latest progress and ongoing challenges [J]. Current Opinion in Rheumatology, 2023, 35(2): 128-134. [3] Reginster JY. The prevalence and burden of arthritis [J]. Rheumatology, 2002, 41: 3-6. [4] Mobasheri A. The future of osteoarthritis therapeutics: emerging biological therapy [J]. Current Rheumatology Reports, 2013, 15(12): 385. [5] Xia Bingjiang, Chen Di, Zhang Jushi, et al. Osteoarthritis pathogenesis: a review of molecular mechanisms [J]. Calcified Tissue International, 2014, 95(6): 495-505. [6] Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis a review [J]. Jama-Journal of the American Medical Association, 2021, 325(6): 568-578. [7] Yue L, Berman J. What is osteoarthritis? [J]. Journal of the American Medical Association, 2022, 327(13): 1300. [8] 陈易杨,王越业. 关节炎发病机制及治疗的研究进展 [J]. 中国处方药, 2023, 21(1): 174-181. [9] Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation [J]. N Engl J Med, 1994, 331(14): 889-895. [10] Li Jiadong, Zhang Hao, Han Yafei, et al. Targeted and responsive biomaterials in osteoarthritis [J]. Theranostics, 2023, 13(3): 931-954. [11] Jiang Yingying, Li Jiadong, Xue Xu, et al. Engineered extracellular vesicles for bone therapy [J]. Nano Today, 2022, 44: 101487. [12] Conaghan PG, Cook AD, Hamilton JA, et al. Therapeutic options for targeting inflammatory osteoarthritis pain [J]. Nature Reviews Rheumatology, 2019, 15(6): 355-363. [13] Abramoff B, Caldera FE. Osteoarthritis: pathology, diagnosis, and treatment options [J]. Medical Clinics, 2020, 104(2): 293-311. [14] Ren Xiaoxiang, Liu Han, Wu Xiamin, et al. Reactive oxygen species (ROS)-responsive biomaterials for the treatment of bone-related diseases [J]. Frontiers in Bioengineering and Biotechnology, 2022, 9: 820468. [15] Laev SS, Salakhutdinov NF. Anti-arthritic agents: progress and potential [J]. Bioorg Med Chem, 2015, 23(13): 3059-3080. [16] Zhou Dongyang, Zhou Fengjin, Sheng Shihao, et al. Intra-articular nanodrug delivery strategies for treating osteoarthritis [J]. Drug Discovery Today, 2023, 28(3): 103482. [17] 郑珊珊,蔡悦,龚瑜贝,等. 纳米载体用于包载生物活性多肽的研究进展 [J]. 中国生物医学工程学报, 2023, 42(2): 242-251. [18] Field LD, Delehanty JB, Chen Y, et al. Peptides for specifically targeting nanoparticles to cellular organelles: quo vadis? [J]. Acc Chem Res, 2015, 48(5): 1380-1390. [19] 李怡静,龚雪峰,王冬,等. 基于多肽的药物递送系统研究进展 [J]. 高分子学报, 2022, 53(5): 445-456. [20] Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions [J]. Bioorg Med Chem, 2018, 26(10): 2700-2707. [21] Rothenfluh DA, Bermudez H, O′Neil CP, et al. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage [J]. Nat Mater, 2008, 7(3): 248-254. [22] Pi Yanbin, Zhang Xin, Shi Junjun, et al. Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display [J]. Biomaterials, 2011, 32(26): 6324-6332. [23] Zhao Yipu, Deng Xudong, Tan Shenxing, et al. Co-polymer carrier with dual advantages of cartilage-penetrating and targeting improves delivery and efficacy of microrna treatment of osteoarthritis [J]. Advanced Healthcare Materials, 2023, 12(6): 2202143. [24] Mi ZB, Lu XL, Mai JC, et al. Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium [J]. Molecular Therapy, 2003, 8(2): 295-305. [25] Castro LMM, Sequeira A, García AJ, et al. Articular cartilage- and synoviocyte-binding poly(ethylene glycol) nanocomposite microgels as intra-articular drug delivery vehicles for the treatment of osteoarthritis [J]. Acs Biomaterials Science & Engineering, 2020, 6(9): 5084-5095. [26] Stoltenburg R, Reinemann C, Strehlitz B. SELEX-A (r)evolutionary method to generate high-affinity nucleic acid ligands [J]. Biomol Eng, 2007, 24(4): 381-403. [27] Schofield P, Taylor AI, Rihon J, et al. Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif [J]. Nucleic Acids Res, 2023, 51(15): 7736-7748. [28] Zhu Guizhi, Chen Xiaoyuan. Aptamer-based targeted therapy [J]. Adv Drug Delivery Rev, 2018, 134: 65-78. [29] Chen Xiang, Zhang Lei, Shao Xiaoyan, et al. Specific clearance of senescent synoviocytes suppresses the development of osteoarthritis based on aptamer-functionalized targeted drug delivery system [J]. Adv Funct Mater, 2022, 32(17): 2109460. [30] Tio L, Orellana C, Pérez-García S, et al. Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients [J]. Medicina Clinica, 2017, 149(1): 9-16. [31] Corradetti B, Taraballi F, Minardi S, et al. Chondroitin sulfate immobilized on a biomimetic scaffold modulates inflammation while driving chondrogenesis [J]. Stem Cells Translational Medicine, 2016, 5(5): 670-682. [32] Lee JY, Lee SH, Kim HJ, et al. The preventive inhibition of chondroitin sulfate against the CCI 4-lnduced oxidative stress of subcellular level [J]. Arch Pharmacal Res, 2004, 27: 340-345. [33] Sobal G, Velusamy K, Kosik S, et al. Preclinical evaluation of 99mTc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis [J]. Nuclear Medicine and Biology, 2016, 43(6): 339-346. [34] Sobal G, Dorotka R, Menzel J, et al. Uptake studies with chondrotropic 99mTc-chondroitin sulfate in articular cartilage. Implications for imaging osteoarthritis in the knee [J]. Nuclear Medicine and Biology, 2013, 40(8): 1013-1017. [35] Bishnoi M, Jain A, Hurkat P, et al. Aceclofenac-loaded chondroitin sulfate conjugated SLNs for effective management of osteoarthritis [J]. J Drug Targeting, 2014, 22(9): 805-812. [36] Ebada HMK, Nasra MMA, Nassra RA, et al. Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment [J]. Drug Delivery, 2022, 29(1): 652-663. [37] Liu Hua, Cai Zhenwei, Wang Fei, et al. Colon-targeted adhesive hydrogel microsphere for regulation of gut immunity and flora [J]. Advanced Science, 2021, 8(18):2101619. [38] Choi KY, Han HS, Lee ES, et al. Hyaluronic acid-based activatable nanomaterials for stimuli-responsive imaging and therapeutics: Beyond CD44-mediated drug delivery [J]. Adv Mater, 2019, 31(34): 1803549. [39] Lu KY, Lin PY, Chuang EY, et al. H2O2-depleting and O2-generating selenium nanoparticles for fluorescence imaging and photodynamic treatment of proinflammatory-activated macrophages [J]. ACS Appl Mater Interfaces, 2017, 9(6): 5158-5172. [40] Li Xiaoxiao, Li Xingchen, Yang Jielai, et al. In situ sustained macrophage-targeted nanomicelle-hydrogel microspheres for inhibiting osteoarthritis [J]. Research, 2023, 6: 0131. [41] Yang Guangzhen, Fan Mengni, Zhu Jingwu, et al. A multifunctional anti-inflammatory drug that can specifically target activated macrophages, massively deplete intracellular H2O2, and produce large amounts CO for a highly efficient treatment of osteoarthritis [J]. Biomaterials, 2020, 255: 120155. [42] Ruan MZ, Erez A, Guse K, et al. Proteoglycan 4 expression protects against the development of osteoarthritis [J]. Sci Transl Med, 2013, 21: S18. [43] Cho H, Kim BJ, Park SH, et al. Noninvasive visualization of early osteoarthritic cartilage using targeted nanosomes in a destabilization of the medial meniscus mouse model [J]. Int J Nanomed, 2018, 13: 1215-1224. [44] Bedingfield SK, Colazo JM, Yu F, et al. Amelioration of post-traumatic osteoarthritis via nanoparticle depots delivering small interfering RNA to damaged cartilage [J]. Nature Biomedical Engineering, 2021, 5(9): 1069-1083. [45] Wang Huaijin, Liu Ying, He Ruiqing, et al. Cell membrane biomimetic nanoparticles for inflammation and cancer targeting in drug delivery [J]. Biomaterials Science, 2020, 8(2): 552-568. [46] Chen HY, Deng J, Wang Y, et al. Hybrid cell membrane-coated nanoparticles: a multifunctional biomimetic platform for cancer diagnosis and therapy [J]. Acta Biomater, 2020, 112: 1-13. [47] Yang Lei, Liu Yuxiao, Shou Xin, et al. Bio-inspired lubricant drug delivery particles for the treatment of osteoarthritis [J]. Nanoscale, 2020, 12(32): 17093-17102. [48] Fang RH, Jiang Y, Fang JC, et al. Cell membrane-derived nanomaterials for biomedical applications [J]. Biomaterials, 2017, 128: 69-83. [49] Nguyen PHD, Jayasinghe MK, Le AH, et al. Advances in drug delivery systems based on red blood cells and their membrane-derived nanoparticlese [J]. Acs Nano, 2023, 17(6): 5187-5210. [50] Manferdini C, Paolella F, Gabusi E, et al. Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation [J]. Osteoarthritis and Cartilage, 2017, 25(7): 1161-1171. [51] 单沁. 骨组织工程中调节巨噬细胞行为促进骨愈合的策略 [J]. 中国生物医学工程学报, 2022, 41(5): 614-620. [52] Ma Yandong, Yang Haiyuan, Zong Xiaoqing, et al. Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics [J]. Biomaterials, 2021, 274: 120865. [53] Zhou Kai, Yang Chengli, Shi Kun, et al. Activated macrophage membrane-coated nanoparticles relieve osteoarthritis-induced synovitis and joint damage [J]. Biomaterials, 2023, 295: 122036. [54] Yu Qianqin, Huang Yuqin, Chen Xun, et al. A neutrophil cell membrane-biomimetic nanoplatform based on l-arginine nanoparticles for early osteoarthritis diagnosis and nitric oxide therapy [J]. Nanoscale, 2022, 14(32): 11619-11634. [55] Deng Caifeng, Chen Yuxiao, Zhao Xuan, et al. Apoptotic neutrophil membrane-camouflaged liposomes for dually targeting synovial macrophages and fibroblasts to attenuate osteoarthritis [J]. ACS Appl Mater Interfaces, 2023, 15(33): 39064-39080. [56] Duan Li, Xu Xiao, Xu Limei, et al. Exosome-mediated drug delivery for cell-free therapy of osteoarthritis [J]. Curr Med Chem, 2021, 28(31): 6458-6483. [57] D'Atri D, Zerrillo L, Garcia J, et al. Nanoghosts: mesenchymal stem cells derived nanoparticles as a unique approach for cartilage regeneration [J]. J Controlled Release, 2021, 337: 472-481. [58] Barteneva NS, Maltsev N, Vorobjev IA. Microvesicles and intercellular communication in the context of parasitism [J]. Frontiers in Cellular and Infection Microbiology, 2013, 3: 49. [59] Paolicelli RC, Bergamini G, Rajendran L. Cell-to-cell communication by extracellular vesicles: focus on microglia [J]. Neuroscience, 2019, 405: 148-157. [60] Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more [J]. Trends Cell Biol, 2009, 19(2): 43-51. [61] Colombini A, Ragni E, Mortati L, et al. Adipose-derived mesenchymal stromal cells treated with interleukin 1 beta produced chondro-protective vesicles able to fast penetrate in cartilage [J]. Cells, 2021, 10(5): 1180. [62] Fang RH, Kroll AV, Gao WW, et al. Cell membrane coating nanotechnology [J]. Adv Mater, 2018, 30(23): 1706759. [63] Xue Xu, Liu Han, Wang Sicheng, et al. Neutrophil-erythrocyte hybrid membrane-coated hollow copper sulfide nanoparticles for targeted and photothermal/anti-inflammatory therapy of osteoarthritis [J]. Composites Part B, 2022, 237: 109855. [64] Edis Z, Wang J, Waqas MK, et al. Nanocarriers-mediated drug delivery systems for anticancer agents: an overview and perspectives [J]. Int J Nanomed, 2021, 16: 1313-1330.
