TY - JOUR
AU1 - Qamar,, Naila
AU2 - Arif,, Ammara
AU3 - Bhatti,, Attya
AU4 - John,, Peter
AB - Abstract RA is a multifactorial autoimmune inflammatory disease characterized by synovitis, bone destruction and joint dysfunction that leads to shortening of lifespan and increased mortality rates. Currently available treatments of RA, by controlling various symptoms, only delay disease progression and have their own side effects. Consequently, there is the need for a novel therapeutic strategy that offers a more sustainable and biocompatible solution. Nanomedicine is a modern branch of nanobiotechnology that provides targeted therapy to inflamed rheumatic joints and thus prevents unwanted off-target side effects. This review highlights various nanotheranostic and nanotherapeutic strategies that are currently being used for the treatment of RA. nanomedicine, nanotheranostics, nanotherapeutics, rheumatoid arthritis, targeted drug delivery Rheumatology key messages Adverse effects restrict the effectiveness of existing treatment modalities for RA. Nanomedicine enhances the bioavailability and bioactivity of drugs through selective targeting. Introduction RA is a common polyarticular autoimmune inflammatory disease described by cartilage and bone destruction in the synovial joints leading to joint impairment and decrease in life expectancy [1–3]. Although the exact mechanism of RA is still unclear, environmental and genetic factors are known to contribute to disease susceptibility [1]. In the synovial tissues, the immune system releases certain enzymes and chemicals that lead to erosion of bones and cartilage, which is one of the major factors resulting in arthritis, a disease affecting numerous joints of the body including the small joints of the hands, wrists, elbows, shoulders, knees, hip, cervical spine, ankles and feet [4, 5, 8]. The global prevalence of RA is about 0.5–1% [6–9]; in the developing countries its prevalence varies and various studies indicate that the Western countries have a greater prevalence of RA than others [7, 10]. It is three times more common among females as compared with males [6, 11] and more prevalent in women above 65 years of age, which could be attributed to hormonal changes [12]. The existing treatments of RA, such as NSAIDs, DMARDs, glucocorticoids and biologic drugs [1, 6], either produce symptomatic relief or alter the disease process. Although these are effective treatments, their use is restricted because of their damaging side effects, such as cardiac complications, gastrointestinal damage and ulcers, along with immunosuppression that leads to the development of opportunistic infections [1]. Etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) are some of the biologics used to treat RA [6, 13] and many other inflammatory conditions. Despite recent medical advances, there is still an unmet need to develop treatments for RA because of safety and efficacy concerns associated with the currently available drugs [13]. Adverse consequences due to non-selective activity of the currently available RA therapeutics can be reduced by encapsulating these bioactive molecules in nanocarriers for a more targeted approach to delivering the drugs at the desired site of action (i.e. the joints) by avoiding frequent or high dosing, to achieve an effective drug concentration locally [2, 14]. Furthermore, nanocarriers can be engineered to protect these bioactive molecules from degradation, thus increasing their bioavailability, while decreasing off-target side effects. There can be targeting of certain specific receptors or of macrophage uptake to invade diseased tissues such as inflamed joints [13, 15]; and the uptake of nanocarriers by spleen and liver can be prevented by modifying their physiochemical properties, such as enhanced penetration through biological barriers and encapsulation [16]. Once the nanocarriers reach the target tissue or organ, the drug can be released in a controlled fashion depending on the pH, temperature, solubility, redox conditions, etc. Scientists have been successful in making nanomaterials that respond to these physical or biological stimuli, termed ‘intelligent’ or ‘smart’ delivery systems [17]. This allows investigators to examine or re-examine bioactive molecules that were previously thought to be too toxic to deliver through a systemic route [14]. Nanomedicine is the use of nanotechnology in medicine to ease the diagnosis, treatment and monitoring of treatment [18] by using nanoparticles, dendrimers, polymeric micelles, drug-loaded liposomes [19], nanocapsules and nanogels. In addition polymer–protein conjugates, polymer–drug conjugates and antibodies also come under the umbrella of nanomedicine [13]. The most important phenomenon for the treatment of RA and other chronic inflammatory disorders is enhanced permeability and retention because of the extensive systemic nature of inflammation. Synthesis of nanoparticles that are ideally sized (10–1000 nm) and modification of their surface with appropriate functional groups can help increase their circulation time and hence provide maximum benefit in performing their desired task [20]. The nanomedicine actively or passively accumulates in the inflamed joints through an enhanced permeation and retention effect. The permeation and accumulation of nanomaterials at the site of inflammation is facilitated by disturbed vasculature and decreased lymphatic drainage under inflammatory conditions and at solid tumours through passive targeting. An appropriate receptor-specific ligand is attached to a nanocarrier for precise binding in the case of active targeting, which aids in increased efficacy and reduced systemic side effects [13, 21]. In one approach, theranostics, nanomedicine may open up a new way to associate diagnosis and treatment [22, 23]. Biodegradable, biocompatible and disease-modifying anti-rheumatic nanomedicines (DMARNs) represent a likely therapeutic approach for osteoarthritis and RA. The enhanced bioavailability and bioactivity of DMARNs at the site of inflammation is due to the combination of unique physiochemical properties of nanocarriers and the pathophysiological properties of inflamed joints, through selective targeting and minimization of off-target adverse effects. Therefore, nanomedicine not only reduces the drug dosage but also decreases the treatment duration [24]. The surface modifications of nanomaterials such as nanoparticles (metallic, polymeric, solid-lipid nanoparticles), nanocomposites, nanoconjugates, nanocarriers, nanowhiskers, micelles, specifically coated nanoparticles and receptor-targeted nanoparticles allow the selective targeting of inflamed joints through the linked drugs, ligands, and prognostic or diagnostic markers, as illustrated in Fig. 1. Some of the nanotheranostic and nanotherapeutic approaches utilizing these nanomaterials that have been proved to be effective in RA are summarized in Fig. 2. Fig. 1 Open in new tabDownload slide Role of nanomaterials in amelioration of joint damage Fig. 1 Open in new tabDownload slide Role of nanomaterials in amelioration of joint damage Fig. 2 Open in new tabDownload slide Various theranostic and therapeutic applications of nanomaterials Fig. 2 Open in new tabDownload slide Various theranostic and therapeutic applications of nanomaterials Theranostic approach of nanomedicine for RA Theranostics will enhance the precision and efficacy of treatment by shifting the generalized approach of existing clinical standards to personalized procedures. Therefore, theranostics has a major role in diseases, such as RA, cancer, infection and cardiac disorders, that need personalized methods for treatment and monitoring. This personalized approach assists the physician to modify the treatment depending on the patient’s needs and responses, thus preventing the adverse effects associated with drugs, such as those at high dosage, that may lead to drug resistance, relapse and incomplete remission [22]. Nanotechnology is being considered for the development of new ways to diagnose, fight and monitor the progress of treatment, hence providing a non-invasive and definite imaging tool for RA [25]. Bio-imaging and photodynamic therapy through nanocomposites in RA Nanocomposites are thought of as materials of the 21st century due to their unique design and combination of properties. Having at least one phase in the nanometre range, they appear to be appropriate alternatives to coping with the challenges associated with monolithics and microcomposites [26]. The timely diagnosis and treatment of RA is still a challenge, but Zhao et al. [28] have revealed the possibility of employing Tetra Sulphonaphenyl porphyrin with titanium dioxide (TiO2) nanowhiskers (rod like nanostructures) [27], a novel nanocomposite, as an efficient bio-imaging and photodynamic therapeutic agent. The study validated that this nanocomposite solution has an improving effect on RA by decreasing the level of TNF-α and IL-17 in serum, assisted by use of fluorescence imaging to diagnose disease at early stages and to identify biomarkers in the inflamed joints of RA [28]. Magnetic-targeted chemo-photothermal nanotherapy in RA Kim et al. [29] developed methotrexate-loaded plasmonic nanoparticles consisting of gold in the inner- and outermost layers with iron in the middle layer. Furthermore, certain biomolecules were also attached to target the specific site, provide chemo-photothermal therapy and retain the potential to be imaged in vivo. Infra-red irradiation was used to cause heat generation at the inflamed region, owing to resonance, and release the methotrexate. The iron layer in the middle allowed magnetic resonance imaging along with near infrared absorbance imaging. Apart from this, if an external magnetic field was applied, the delivery and retention time of nanoparticles in the inflamed regions could be increased. The study in question was important not only because of the multifunctional nature of nanoparticles, but also due to the small dosage of drug required for therapy with the injected nanoparticles [29]. Combined photodynamic and photothermal therapy in RA Due to efficient penetration of near infrared light in inflamed joints, phototherapy (photodynamic therapy and photothermal therapy) offers new treatment modalities for RA. Unique Cu7.2S4 nanoparticles were prepared by Lu et al. [30] for the treatment of RA, showing that copper-based nanomaterials can serve as photothermal agents as well as photosensitizers, and in the meantime copper may stimulate chondrogenesis and osteogenesis [13]. The Cu7.2S4 nanoparticles in combination with 808 nm near infrared light irradiation not only inhibited invasion of inflamed synovium, in vivo release of pro-inflammatory cytokines and erosion of cartilage, but also preserved bone by achieving higher bone to total volume and higher BMD. Hence phototherapy using multipurpose Cu7.2S4 nanoparticles could be a new treatment approach for RA [30]. Nanotheranostic approach for macrophage detection and therapy in RA Pathogenicity, phagocytic nature and abundance are the characteristic features of macrophages that make them potential theranostic targets. Though nanoparticles are phagocytosed by macrophages, in vivo targeting efficacy is influenced by their physicochemical properties such as shape, size, surface charge, functionalization and ligands. Certain receptors expressed on the surface of macrophages are used for active targeting by ligands, namely dextran, mannose, tuftsin and hyaluronate [31]. Heo et al. [32] developed nanoparticles through conjugation of 5β-cholanic acid to a dextran sulphate backbone for selective delivery of methotrexate to the affected joints in RA. By using a simple dialysis method, methotrexate was loaded into the dextran sulphate nanoparticles with an efficiency of 73% and readily endocytosed by macrophages. When administered systemically into the experimental collagen-induced arthritic mice, these nanoparticles efficiently caused about 12-fold increase in inflamed joints indicating their targeted approach. Besides, methotrexate-loaded nanoparticles demonstrated significant therapeutic efficacy in the arthritic mouse model, thus highlighting dextran sulphate nanoparticles as a possible nanomedicine for imaging and therapy of RA [32]. Due to the intrinsic disease-causing ability of macrophages and monocytes, the inflamed vasculature of the joints provides an opportunity for passive-targeting nanotheranostic systems. Due to this property, macrophages can be used as Trojan horses for delivery of drugs and imaging agents at the site of disease [31]. Therapeutic approach of nanomedicine towards RA Nanomedicine and nanocarriers are a new but evolving science where nanoscale materials are employed as a tool for disease diagnosis or for targeted drug delivery in a very precise manner. Targeted delivery of chemotherapeutic, immunotherapeutic and biologic agents in treating numerous diseases is a recent and outstanding application of nanomedicine [33]. Therapeutics based on nanoparticles have great potential to influence the treatment of various human diseases, but instability and early release from nanoparticles decreases the bioavailability of a drug, which impedes its clinical translation [34]. Nanocarriers in treatment of RA Jain et al. [35] designed a nanocarrier by using plasmid DNA-encoded IL-10, an anti-inflammatory cytokine, encapsulated in alginate-based nanoparticles, and the surface was modified by tuftsin peptide to attain selective targeting of macrophages. The effect of the targeted approach with this nanocarrier was observed in the inflamed paws of arthritic rats after intraperitoneal administration. This treatment significantly reprogrammed ∼66% of total synovial macrophages from the M1 to M2 phenotype and reduced the expression of pro-inflammatory cytokines like IL-1β, IL-6 and TNF-α, thus preventing the progression of inflammation at the effected joints. In conclusion, IL-10 plasmid DNA-loaded alginate nanoparticles can effectively repolarize macrophages from the M1 to M2 phenotype, presenting a new therapeutic approach for severe inflammatory conditions [35]. A pH-responsive nanocarrier has been developed comprising lipids, a hydrophobic core of poly(cyclohexane-1,4-diylacetone dimethylene ketal) and poly(lactic-co-glycolic acid) (PLGA), a hydrophilic shell of polyethylene glycol, and the targeting ligand (folic acid) around this shell. Nanoparticles encapsulating methotrexate revealed a pH-responsive in vitro distribution. The methotrexate-loaded nanoparticles significantly exhibited cellular uptake and enhanced cytotoxicity to activated macrophages confirming their therapeutic efficacy in an experimental arthritic rat, suggesting this system would be a promising therapy for RA [36]. In another study, the scientists encapsulated betamethasone phosphate with polymeric nanoparticles of stealth nanosteroids, which were not only biodegradable but also showed enhanced biocompatibility. The results showed that stealth nanosteroids of certain specific types had a remarkable therapeutic effect on experimental arthritis due to their constant release in situ and their sustained circulation in the blood [37]. Nanocomplexes in treatment of RA A nanocomplex of thiolated glycol chitosan (tGC) nanoparticles with polymerized small interfering RNA (siRNA) targeting TNF-α was designed by Lee et al. [38] for the treatment of RA. The polysiRNA-tGC nanoparticles showed rapid cellular uptake in a macrophage culture system and efficiently silenced the TNF-α gene in vitro. Significantly this nanocomplex exhibited high accumulation at the inflamed joints of collagen-induced arthritic mice. Analysis by microcomputed tomography and a MMP3-specific probe revealed that intravenous administration of this nanocomplex inhibited inflammation and erosion of bones in arthritic mice significantly as compared with methotrexate. Hence, the accessibility of polysiRNA-tGC nanoparticle therapy that targets specific cytokines marks the beginning of a new era of therapeutics for RA [38]. Zhou et al. [39] designed a nanocomplex by combining melittin-derived cationic peptide with siRNA targeting subunit p65 of NF-κB (p5RHH-p65). Administration of this nanocomplex specifically abrogated the cellular influx and expression of inflammatory cytokines at the inflamed joints, thereby preserving cartilage integrity and preventing bone erosion. Thus the p5RHH-p65 siRNA complex effectively repressed the inflammatory responses in arthritis without altering the expression of p65 in off-target organs [39]. Vasoactive intestinal peptide in treatment of RA Sterically stabilized micelles (SSMs) comprise polyethylene glycolylated phospholipids and can help carry water-insoluble small molecules and peptide drugs to the desired site. Vasoactive intestinal peptide (VIP) is a neurotransmitter and neuromodulator that is secreted from nerve terminals [40, 41]. The interaction of SSMs with VIP is an innovative approach designed by Sethi et al. [42] to treat RA that protects the peptide from inactivation and degradation in body fluids and increases its circulation time. Treatment by selective low doses of VIP–SSM efficiently reduced the incidence and arthritic severity in a mouse model by completely voiding bone and cartilage destruction and swelling of joints without any off-target adverse effects. Hence, low doses of VIP–SSM proved a novel biocompatible and disease-modifying nanomedicine for RA as it efficiently down-regulated the immune and inflammatory responses in arthritic mice [42]. Nanoparticles in treatment of RA Nanoparticles are composed of inorganic or organic material and are of diameter 1–100 nm [19, 43]; they exhibit novel and unique properties as compared with bulk materials but also exhibit considerable toxicity because of their high reactivity with chemicals, increased cell permeability, and their large surface area and inner pore dimensions. The physiochemical properties of nanoparticles assist the binding of cellular, blood and protein components that ease their interactions with immune cells eliciting the immune response [43]. Gold nanoparticles There is the possibility of using gold nanoparticles exhibiting anti-angiogenic and anti-inflammatory properties as an effective treatment of RA owing to their decreased adverse effects [44]. According to the report of Mahalakshmi et al., gold nanoparticles coated with citrate exhibit anti-inflammatory properties by repressing the cell responses elicited by IL-β, an inflammatory cytokine acting as a mediator of immunological responses in inflammatory conditions such as RA, with no toxic effects on organ or cellular functions [43]. Poly(D,L-lactic/glycolic acid) nanoparticles Poly(D,L-lactic/glycolic acid) nanoparticles can control release of a drug and extend its circulation time. Higaki et al. created nanoparticles of betamethasone by using PLGA particles of around 100–200 nm in size and found this system to be more efficient in reducing the inflammatory response in arthritis-induced mice and rats by intravenous administration as compared with free glucocorticoids [45]. Solid-lipid nanoparticles The long-term use of glucocorticoids to treat RA leads to severe adverse effects due to their systemic distribution, but Zhou et al. [46] developed a targeted system by encapsulating the glucocorticoid prednisolone within hyaluronic acid-coated solid-lipid nanoparticles. The surfaces of synovial lymphocytes, fibroblasts and macrophages overexpressed the receptor for hyaluronic acid in the arthritic joints. After intravenous administration the hyaluronic acid–solid-lipid nanoparticles–prednisolone particles accumulated in the inflamed joints of collagen-induced arthritic mice and persisted for a long time in the circulation. These particles preserved the cartilage and bone integrity and reduced joint swelling and the inflammatory cytokine levels in serum, rendering these particles an efficient and safe therapy for inflammatory diseases [46]. Conjugated nanoparticles Conjugated nanoparticles were designed by Hwang et al. [47] by conjugating cyclodextrin polymer to the drug α-methylprednisone, and self-assembly of this conjugate gave rise to nanoparticles of size 27 nm. In vitro as well as in vivo assessments were conducted and multiple parameters were considered such as the half-life of the conjugate and release kinetics of the drug. It was observed that methylprednisone when administered on its own demonstrated minimal efficacy, whereas a reduction in arthritic score was observed in an animal model treated with conjugate. Additionally, reduced dorsoplantar swelling and a decrease in synovitis and pannus formation was also seen. In a nutshell, this research concluded that the conjugation method not only increased the efficacy of treatment but also presented a more convenient method of managing RA, as lower doses and a reduced frequency of administration of the drug were required in this particular scenario [47]. Folate-targeted nanoparticles Thomas et al. [48] utilized folate-targeted nanoparticles with an in vitro study using a macrophage cell line and an in vivo study using the collagen-induced arthritic rat model. It was found that the aforementioned conjugated nanoparticles not only acted as an effective anti-inflammatory agent but also helped in minimizing arthritic inflammatory parameters like cartilage damage, ankle swelling, paw volume and bone resorption [48]. Neutrophil-membrane-coated nanoparticles In spite of recent clinical progress, the treatment of RA remains inadequate due to the complexity of cytokine interactions and the multiplicity of their targets. For the management of RA, a broad spectrum anti-inflammatory approach based on nanoparticles was presented by Zhang et al. [49]. They prepared membrane-coated nanoparticles by the fusion of neutrophil membrane to polymeric cores and revealed that these nanoparticles can suppress synovial inflammation, deactivate pro-inflammatory cytokines, offer strong chondro-protection against inflamed joints and target the deep matrix of the cartilage. In the collagen-induced and human transgenic arthritic mouse models, these membrane-coated nanoparticles demonstrate a substantial therapeutic efficiency by suppressing arthritic severity and improving joint damage [49]. Limitations of nanomedicine Regardless of various advantages there are some limitations of using nanomedicine, particularly the possibility of generating toxicity at the cellular level [13, 45]. Upon cellular exposure, nanomaterials lead to the production of free radicals such as reactive nitrogen species and reactive oxygen species [6] by damaging cells at various levels [43]. Nanomaterials must be evaluated for their toxic effects to assess their safety, along with the therapeutic agent itself. This may be an expensive process, decreasing the number of nanomedicines that reach clinical trial [13]. The opsonization of intravenously administered nanoparticles decreases their circulation time, thus affecting the drug-delivery efficacy of nanomedicine at the inflamed site. The disturbed vasculature in the inflamed joints is also a limiting factor. For example during inflammation certain matrix-degrading enzymes released by endothelial cells are adsorbed and migrate through the basal membrane and lead to angiogenesis; circulating nanomedicine targets this disturbed vasculature to eradicate the angiogenesis or stop its further spread across the endothelium to access the joint cavity and other sites of inflammation [21]. Conclusion The most remarkable quality of nanostructures is the margin of adaptability in their blueprint. Not only can they be engineered to carry substances of choice, but they can also be rendered more biocompatible by appropriate functionalization procedures. As a result of this freedom, bioscientists have been able to develop more targeted, biocompatible and biodegradable nanomedicines, which is a step towards providing a sustainable solution to the long-standing problem of RA. The novel nanotheranostic and nanotherapeutic strategies being researched not only retain the potential to specifically target rheumatic inflammation sites but could also reduce the dose and administration frequency of drugs to a minimum. Furthermore, the diverse applications of nanostructures discussed above have the potential to be utilized for the prevention, therapy and elimination of other inflammatory disorders as well. Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest. References 1 Umar S, , Asif M, , Sajad M et al. Anti-inflammatory and antioxidant activity of Trachyspermum ammi seeds in collagen induced arthritis in rats . J Drug Dev Res 2012 ; 4 : 210 – 19 . WorldCat 2 Pham CT. Nanotherapeutic approaches for the treatment of rheumatoid arthritis . Wiley Interdiscipl Rev Nanomed Nanobiotechnol 2011 ; 3 : 607 – 19 . Google Scholar Crossref Search ADS WorldCat 3 Rahman M, , Beg S, , Sharma G et al. Emergence of lipid-based vesicular carriers as nanoscale pharmacotherapy in rheumatoid arthritis . Recent Patents Nanomed 2015 ; 5 : 111 – 21 . Google Scholar Crossref Search ADS WorldCat 4 Kapoor B, , Singh SK, , Gulati M, , Gupta R, , Vaidya Y. Application of liposomes in treatment of rheumatoid arthritis: quo vadis . Scientific World Journal 2014 ; 2014 : 978351 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Chandrasekar R , Chandrasekar S. Natural herbal treatment for rheumatoid arthritis – a review . Int J Pharm Sci Res 2017 ; 8 : 368 – 84 . WorldCat 6 Dolati S, , Sadreddini S, , Rostamzadeh D, , Ahmadi M, , Jadidi-Niaragh F, , Yousefi M. Utilization of nanoparticle technology in rheumatoid arthritis treatment . Biomed Pharmacother 2016 ; 80 : 30 – 41 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Alam SM, , Kidwai AA, , Jafri SR et al. Epidemiology of rheumatoid arthritis in a tertiary care unit, Karachi, Pakistan . J Pak Med Assoc 2011;61:123–6. WorldCat 8 Guo Q, , Wang Y, , Xu D, , Nossent J, , Pavlos NJ, , Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies . Bone Res 2018 ; 6 : 15 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Firestein GSJN. Evolving concepts of rheumatoid arthritis . Nature 2003 ; 423 : 356 – 61 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Nogueira E , Gomes AC , Preto A et al. Folate-targeted nanoparticles for rheumatoid arthritis therapy . Nanomedicine 2016 ; 12 : 1113 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Doan T , Massarotti E. Rheumatoid arthritis: an overview of new and emerging therapies . J Clin Pharmacol 2005 ; 45 : 751 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Symmons D, , Turner G, , Webb R et al. The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century . Rheumatology 2002 ; 41 : 793 – 800 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Prasad LK , O'Mary H , Cui ZJN. Nanomedicine delivers promising treatments for rheumatoid arthritis . Nanomedicine (Lond) 2015 ; 10 : 2063 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Ngobili TA , Daniele MA. Nanoparticles and direct immunosuppression . Exp Biol Med 2016 ; 241 : 1064 – 73 . Google Scholar Crossref Search ADS WorldCat 15 Jiang Y , Fang RH , Zhang L. Biomimetic nanosponges for treating antibody-mediated autoimmune diseases . Bioconjug Chem 2018 ; 29 : 870 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Rahman M, , Sharma G, , Thakur K et al. Emerging advances in nanomedicine as a nanoscale pharmacotherapy in rheumatoid arthritis: state of the art . Curr Top Med Chem 2017 ; 17 : 162 – 73 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Liu J , Huang Y , Kumar A et al. pH-sensitive nano-systems for drug delivery in cancer therapy . Biotechnol Adv 2014 ; 32 : 693 – 710 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Kunjachan S , Ehling J , Storm G et al. Noninvasive imaging of nanomedicines and nanotheranostics: principles, progress, and prospects . Chem Rev 2015 ; 115 : 10907 – 37 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Oliveira IM, , Gonçalves C, , Reis RL, , Oliveira JM. Engineering nanoparticles for targeting rheumatoid arthritis: past, present, and future trends . Nano Res 2018 ; 11 : 4489 – 506 . Google Scholar Crossref Search ADS WorldCat 20 Katsuki S , Matoba T , Koga J-I et al. Anti-inflammatory nanomedicine for cardiovascular disease . Front Cardiovasc Med 2017 ; 4 : 87 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Chen M, , Daddy JCKA , Xiao Y, , Ping Q, , Zong L. Advanced nanomedicine for rheumatoid arthritis treatment: focus on active targeting . Expert Opin Drug Deliv 2017 ; 14 : 1141 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Pedrosa P , Vinhas R , Fernandes A et al. Gold nanotheranostics: proof-of-concept or clinical tool? Nanomaterials 2015 ; 5 : 1853 – 79 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Sarmento B , Sarmento M. Nanomedicines for increased specificity and therapeutic efficacy of rheumatoid arthritis . Eur Med J Rheumatol 2017 ; 4 : 98 – 102 . Google Scholar Crossref Search ADS WorldCat 24 Rubinstein I , Weinberg GL. Nanomedicines for chronic non-infectious arthritis: the clinician's perspective . Nanomedicine 2012 ; 8 : S77 – 82 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Mura S , Couvreur P. Nanotheranostics for personalized medicine . Adv Drug Delivery Rev 2012 ; 64 : 1394 – 416 . Google Scholar Crossref Search ADS WorldCat 26 Camargo PHC , Satyanarayana KG , Wypych F. Nanocomposites: synthesis, structure, properties and new application opportunities . Mater Res 2009 ; 12 : 1 – 39 . Google Scholar Crossref Search ADS WorldCat 27 Eichhorn SJ. Cellulose nanowhiskers: promising materials for advanced applications . Soft Matter 2011 ; 7 : 303 – 15 . Google Scholar Crossref Search ADS WorldCat 28 Zhao C , Ur Rehman F , Yang Y et al. Bio-imaging and photodynamic therapy with tetra sulphonatophenyl porphyrin (TSPP)-TiO2 nanowhiskers: new approaches in rheumatoid arthritis theranostics . Sci Rep 2015 ; 5 : 11518 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Kim HJ , Lee S-M , Park K-H et al. Drug-loaded gold/iron/gold plasmonic nanoparticles for magnetic targeted chemo-photothermal treatment of rheumatoid arthritis . Biomaterials 2015 ; 61 : 95 – 102 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Lu Y, , Li L, , Lin Z et al. A new treatment modality for rheumatoid arthritis: combined photothermal and photodynamic therapy using Cu7.2S4 nanoparticles . Adv Healthcare Mater 2018 ; 14 : 1800013 . Google Scholar Crossref Search ADS WorldCat 31 Patel SK , Janjic JM. Macrophage targeted theranostics as personalized nanomedicine strategies for inflammatory diseases . Theranostics 2015 ; 5 : 150 – 72 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Heo R , You DG , Um W et al. Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis . Biomaterials 2017 ; 131 : 15 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 33 Patra JK, , Das G, , Fraceto LF et al. Nano based drug delivery systems: recent developments and future prospects . J Nanobiotechnol 2018 ; 16 : 71 . Google Scholar Crossref Search ADS WorldCat 34 Zhou H-F , Yan H , Senpan A et al. Suppression of inflammation in a mouse model of rheumatoid arthritis using targeted lipase-labile Fumagillin prodrug nanoparticles . Biomaterials 2012 ; 33 : 8632 – 40 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Jain S , Tran T-H , Amiji M. Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis . Biomaterials 2015 ; 61 : 162 – 77 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Zhao J , Zhao M , Yu C et al. Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis . Int J Nanomed 2017 ; 12 : 6735 . Google Scholar Crossref Search ADS WorldCat 37 Ishihara T , Kubota T , Choi T et al. Treatment of experimental arthritis with stealth-type polymeric nanoparticles encapsulating betamethasone phosphate . J Pharmacol Exp Ther 2009 ; 329 : 412 – 17 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Lee SJ , Lee A , Hwang SR et al. TNF-α gene silencing using polymerized siRNA/thiolated glycol chitosan nanoparticles for rheumatoid arthritis . Mol Ther 2014 ; 22 : 397 – 408 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Zhou H-F , Yan H , Pan H et al. Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental arthritis . J Clin Invest 2014 ; 124 : 4363 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Liddle RA , Goldfine I , Williams JJG. Bioassay of plasma cholecystokinin in rats: effects of food, trypsin inhibitor, and alcohol . Gastroenterology 1984 ; 87 : 542 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Onyuksel H. Lipid based sterically stabilized micelles as effective drug carriers for cancer and inflammatory diseases . Pharmaceut Anal Acta 2013 ; 4 : 62 . WorldCat 42 Sethi V , Rubinstein I , Kuzmis A et al. Novel, biocompatible, and disease modifying VIP nanomedicine for rheumatoid arthritis . Mol Pharm 2013 ; 10 : 728 – 38 . Google Scholar Crossref Search ADS PubMed WorldCat 43 Mahalakshmi A , Santhi K , Nidavani R. Rheumatoid arthritis and nanotherapeutics . European Journal of Pharmaceutical and Medical Research 2016;3:142–9. WorldCat 44 Hornos Carneiro MF , Barbosa F Jr . Gold nanoparticles: a critical review of therapeutic applications and toxicological aspects . J Toxicol Environ Health B Crit Rev 2016 ; 19 : 129 – 48 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Higaki M, Ishihara T, Izumo N et al. Treatment of experimental arthritis with poly(D, L-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate. Ann Rheum Dis 2005;64:1132–6. 46 Zhou M , Hou J , Zhong Z et al. Targeted delivery of hyaluronic acid-coated solid lipid nanoparticles for rheumatoid arthritis therapy . Drug Deliv 2018 ; 25 : 716 – 22 . Google Scholar Crossref Search ADS PubMed WorldCat 47 Hwang J , Rodgers K , Oliver JC , Schluep T. α-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy . Int J Nanomed 2008 ; 3 : 359 – 72 . WorldCat 48 Thomas TP, , Goonewardena SN, , Majoros IJ et al. Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis . Arthritis Rheum 2011 ; 63 : 2671 – 80 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Zhang Q, , Dehaini D, , Zhang Y et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis . Nat Nanotechnol 2018 ; 13 : 1182 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Nanomedicine: an emerging era of theranostics and therapeutics for rheumatoid arthritis
JF - Rheumatology
DO - 10.1093/rheumatology/kez286
DA - 2019-10-01
UR - https://www.deepdyve.com/lp/oxford-university-press/nanomedicine-an-emerging-era-of-theranostics-and-therapeutics-for-gNMS83NXti
SP - 1715
VL - 58
IS - 10
DP - DeepDyve
ER -