Monotropein mitigates atopic dermatitis-like skin inflammation through JAK/STAT signaling pathway inhibition.

Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.

Aspalathin, a Primary Rooibos Flavonoid, Alleviates Mast Cell-Mediated Allergic Inflammation by the Inhibition of FcεRI Signaling Pathway.

Mast cells are primary cells initiating allergic inflammation by the release of various allergic mediators, such as histamine and pro-inflammatory cytokines. Aspalathin (ASP) is the predominant flavonoid found exclusively in rooibos, an herb that has been traditionally used in allergy relief therapy. In the present study, we investigated the beneficial effects of ASP on mast cell-mediated allergic inflammation. For in vivo study, two well-known mast cell-mediated local and systemic allergic inflammation mouse models were used: passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis mouse models (ASA). Oral administration of ASP dose-dependently suppressed immunoglobulin (Ig)E-mediated PCA responses evidenced by Evans blue extravasation, ear thickening, and mast cell degranulation. ASP also significantly mitigated ovalbumin-induced ASA responses, including hypothermia, histamine secretion, and the production of IgE and interleukin-4. Notably, ASP was more effective in suppressing allergic inflammation than nothofagin, another prominent flavonoid known as an anti-allergic component of rooibos. The regulatory mechanism of mast cell activation by ASP was clarified using mast cell line and primary cultured mast cells (RBL-2H3 and mouse bone marrow-derived mast cells). ASP reduced IgE-stimulated mast cells degranulation and intracellular calcium influx by the inhibition of FcεRI signaling pathway (Lyn, Fyn, and Syk). Moreover, ASP reduced pro-inflammatory cytokine expressions by inhibiting two major transcription factors, nuclear factor of activated T cells and nuclear factor-κB. Collectively, we proposed that ASP could be a potential therapeutic candidate for the treatment of mast cell-mediated allergic inflammatory diseases.

Ameliorated Skin Inflammation through the Synergistic Effect of Gold Nanorod-Dexamethasone and Photothermal Therapy.

Psoriasis, a prevalent chronic inflammatory skin ailment affecting approximately 2-3% of the global population, is characterized by persistent symptoms. Dexamethasone, a primary corticosteroid for treating psoriasis, demonstrates notable efficacy; however, its limited skin permeation results in documented adverse effects. To address this, the presented study employed a novel strategy to conjugate gold nanorod and dexamethasone and evaluate their potential for mitigating psoriatic inflammation using an imiquimod-induced mouse model and human skin cells. Our findings revealed enhanced cutaneous penetration of gold nanorod and dexamethasone conjugates compared with that of dexamethasone, owing to superior skin penetration. Gold nanorod and dexamethasone conjugates demonstrated an optimal pharmacological impact at minimal dosages without toxicity during extended use. To further enhance the effectiveness of gold nanorod and dexamethasone conjugates, 808 nm near-infrared laser irradiation, which reacts to gold, was additionally applied to achieve thermal elevation to expedite drug skin penetration. Supplementary laser irradiation at 808 nm significantly ameliorated psoriatic symptoms following deep gold nanorod and dexamethasone conjugates penetration. This corresponded with restored peroxisome proliferator-activated receptor-γ levels and accelerated dexamethasone release from the gold nanorod and dexamethasone conjugates complex. These findings highlight the potential of gold nanorod and dexamethasone conjugates to enhance drug penetration through dermal layers, thereby aiding psoriasis treatment. Moreover, its compatibility with photothermal therapy offers prospects for novel therapeutic interventions across various inflammatory skin disorders.

Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier.

The blood-brain barrier (BBB) and blood-tumor barrier (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities to overcome these barriers and enhance drug penetration into the brain parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic field, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery involves using engineered cells as carriers for nanoparticles, taking advantage of their intrinsic migratory and homing capabilities to facilitate the transport of therapeutic payloads across BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, coupled with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery exploits magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive avenue to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM.

Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process is demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nanostar loaded with triamcinolone is conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nanostar significantly elevates the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, is downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell is inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nanostar (Edu-MSCs-AuS-TA) promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain, improve general locomotor activity, and more importantly, induce cartilage regeneration even for severe stages of arthritis model.

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis.

Purpose: Rheumatoid arthritis (RA) is a highly prevalent form of autoimmune disease that affects nearly 1% of the global population by causing severe cartilage damage and inflammation. Despite its prevalence, previous efforts to prevent the perpetuation of RA have been hampered by therapeutics' cytotoxicity and poor delivery to target cells. The present study exploited drug repositioning and nanotechnology to convert metformin, a widely used antidiabetic agent, into an anti-rheumatoid arthritis drug by designing poly(lactic-co-glycolic acid) (PLGA)-based spheres. Moreover, this study also explored the thermal responsiveness of the IL-22 receptor, a key regulator of Th-17, to incorporate photothermal therapy (PTT) into the nanodrug treatment. Materials and Methods: PLGA nanoparticles were synthesized using the solvent evaporation method, and metformin and indocyanine green (ICG) were encapsulated in PLGA in a dropwise manner. The nanodrug's in vitro anti-inflammatory properties were examined in J744 and FLS via real-time PCR. PTT was induced by an 808 nm near-infrared (NIR) laser, and the anti-RA effects of the nanodrug with PTT were evaluated in DBA/1 collagen-induced arthritis (CIA) mice models. Further evaluation of anti-RA properties was carried out using flow cytometry, immunofluorescence analysis, and immunohistochemical analysis. Results: The encapsulation of metformin into PLGA allowed the nanodrug to enter the target cells via macropinocytosis and clathrin-mediated endocytosis. Metformin-encapsulated PLGA (PLGA-MET) demonstrated promising anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), increasing the expression of anti-inflammatory cytokines (IL-10 and IL-4), and promoting the polarization of M1 to M2 macrophages in J774 cells. The treatment of the nanodrug with PTT exhibited more potent anti-inflammatory effects than free metformin or PLGA-MET in CIA mice models. Conclusion: These results demonstrated that PLGA-encapsulated metformin treatment with PTT can effectively ameliorate inflammation in a spatiotemporal manner.

IRF3 Activation in Mast Cells Promotes FcεRI-Mediated Allergic Inflammation.

(1) Background: This study aims to elucidate a novel non-transcriptional action of IRF3 in addition to its role as a transcription factor in mast cell activation and associated allergic inflammation; (2) Methods: For in vitro experiments, mouse bone-marrow-derived mast cells (mBMMCs) and a rat basophilic leukemia cell line (RBL-2H3) were used for investigating the underlying mechanism of IRF3 in mast-cell-mediated allergic inflammation. For in vivo experiments, wild-type and Irf3 knockout mice were used for evaluating IgE-mediated local and systemic anaphylaxis; (3) Results: Passive cutaneous anaphylaxis (PCA)-induced tissues showed highly increased IRF3 activity. In addition, the activation of IRF3 was observed in DNP-HSA-treated mast cells. Phosphorylated IRF3 by DNP-HSA was spatially co-localized with tryptase according to the mast cell activation process, and FcεRI-mediated signaling pathways directly regulated that activity. The alteration of IRF3 affected the production of granule contents in the mast cells and the anaphylaxis responses, including PCA- and ovalbumin-induced active systemic anaphylaxis. Furthermore, IRF3 influenced the post-translational processing of histidine decarboxylase (HDC), which is required for granule maturation; and (4) Conclusion: Through this study, we demonstrated the novel function of IRF3 as an important factor inducing mast cell activation and as an upstream molecule for HDC activity.

Pancreatic Tumor-Targeting Stemsome Therapeutics.

Owing to the intrinsic ability of stem cells to target the tumor environment, stem-cell-membrane-functionalized nanocarriers can target and load active anticancer drugs. In this work, a strategy that focuses on stem cells that self-target pancreatic cancer cells is developed. In particular, malignant deep tumors such as pancreatic cancer cells, one of the intractable tumors that currently have no successful clinical strategy, are available for targeting and destruction. By gaining the targeting ability of stem cells against pancreatic tumor cells, stem cell membranes can encapsulate nano-polylactide-co-glycolide loaded with doxorubicin to target and reduce deep pancreatic tumor tissues. Considering the lack of known target proteins on pancreatic tumor cells, the suggested platform technology can be utilized for targeting any malignant tumors in which surface target receptors are unavailable.

Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs.

Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.

Mucosal delivery of nanovaccine strategy against COVID-19 and its variants.

Despite the global administration of approved COVID-19 vaccines (e.g., ChAdOx1 nCoV-19®, mRNA-1273®, BNT162b2®), the number of infections and fatalities continue to rise at an alarming rate because of the new variants such as Omicron and its subvariants. Including COVID-19 vaccines that are licensed for human use, most of the vaccines that are currently in clinical trials are administered via parenteral route. However, it has been proven that the parenteral vaccines do not induce localized immunity in the upper respiratory mucosal surface, and administration of the currently approved vaccines does not necessarily lead to sterilizing immunity. This further supports the necessity of a mucosal vaccine that blocks the main entrance route of COVID-19: nasal and oral mucosal surfaces. Understanding the mechanism of immune regulation of M cells and dendritic cells and targeting them can be another promising approach for the successful stimulation of the mucosal immune system. This paper reviews the basic mechanisms of the mucosal immunity elicited by mucosal vaccines and summarizes the practical aspects and challenges of nanotechnology-based vaccine platform development, as well as ligand hybrid nanoparticles as potentially effective target delivery agents for mucosal vaccines.

Greater Plasma Protein Adsorption on Mesoporous Silica Nanoparticles Aggravates Atopic Dermatitis.

Purpose: The protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date. Methods: We examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes. Results: We compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression. Conclusion: This study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems.

Portable Cold Atmospheric Plasma Patch-Mediated Skin Anti-Inflammatory Therapy.

Although plasma is a promising technology in various fields, its clinical application is restricted by several limitations. A cold atmospheric plasma (CAP) patch is fabricated to help overcome hurdles, especially when treating skin diseases. This patch has surface dielectric barrier discharge, which generates reactive oxygen species (ROS) and reactive nitrogen species (RNS) on a flexible polymer film surface on which the embedded electrode induces a locally strong electric field. The effect of the CAP patch on psoriasis is also evaluated. The distinct characteristics of psoriasis between the lesion and non-lesion area allow the CAP patch to be suitable for only lesion area for its treatment. The CAP patch induces the opening of calcium channels in keratinocytes, thereby restoring abnormal keratinocyte differentiation and the collapse of the tight junction; thus, alleviating psoriatic symptoms. In addition, the favorable effect is due to the induction of ROS/RNS by the CAP patch, not the electric field generated during plasma generation. The findings indicate that the proposed portable CAP patch can help treat inflammatory skin disorders, especially psoriasis. As this can be used easily as a combination therapy with existing drugs, it may help reduce side effects caused by existing drugs.

Gomisin M2 alleviates psoriasis­like skin inflammation by inhibiting inflammatory signaling pathways.

Psoriasis, a chronic inflammatory skin disease, is characterized by the excessive proliferation and impaired differentiation of epidermal keratinocytes and is accompanied by the increased infiltration of inflammatory cells. The condition requires long­term treatment and has no definitive cure. Hence, supplements and therapeutic agents have been intensely investigated. Gomisin M2 (GM2), a lignan extracted from Schisandra chinensis (Turcz). Baill. (Schisandraceae; S. chinensis), has demonstrated diverse pharmacological properties, including anticancer, anti­inflammatory and antiallergic effects. Based on these findings, the present study examined the effects of GM2 on an imiquimod (IMQ)­induced psoriasis mouse model and on keratinocytes stimulated by tumor necrosis factor (TNF)­α and interferon­Î³. IMQ was topically applied to the back skin of mice for 7 consecutive days, and the mice were orally administered CD. These results showed that the oral administration of GM2 suppressed the symptoms of psoriasis, as evidenced by reductions in skin thickness, psoriasis area severity index scores for psoriasis lesions, transepidermal water loss and myeloperoxidase (MPO)­associated cell infiltration. Furthermore, GM2 reduced the pathologically increased levels of immunoglobulin G2a, MPO and TNF­α in the serum and T helper (Th)1 and Th17 cell populations in the spleen. GM2 decreased the gene expression of inflammatory­related cytokines and chemokines and inhibited the expression of signal transducer and activator of transcription 1 and nuclear factor­κB in the activated keratinocytes. These results suggested that GM2 from S. chinensis is a potential therapeutic candidate to alleviate psoriasis­like skin inflammation.

Ursolic acid inhibits FcεRI-mediated mast cell activation and allergic inflammation.

BACKGROUND: Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FcεRI-mediated mast cell activation and allergic inflammation. METHODS: In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model. RESULTS: We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FcεRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner. CONCLUSIONS: Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FcεRI-mediated mast cell activation.

Structural Deformation of MTX Induced by Nanodrug Conjugation Dictate Intracellular Drug Transport and Drug Efficacy.

BACKGROUND: Understanding structural interactions between the active drug and conjugated nanoparticles is critical for optimizing intracellular drug transport and for increasing nano drug efficacy. In this regard, analyzing the conformational deformation of conjugated drugs surrounding nanoparticles is essential to understand the corresponding nanodrug efficacy. PURPOSE: The objective of this study is to present an optimal synthesis method for efficient drug delivery through a clear structural analysis of nanodrugs according to the type of conjugation. METHODS AND RESULTS: In this study, the structural variation of methotrexate (MTX) surrounding carbon nanotubes, depending on the type of conjugation style, such as covalent and non-covalent (PEGylation) bonds, was investigated. Specifically, covalent bonds of MTX surrounding CNTs induced greater structural deformation compared to non-covalent bonds (ie, PEGylated CNT). CONCLUSION: Greater changes in the structural variations of MTX analyzed by nuclear magnetic resonance (NMR) significantly improved the anti-inflammatory drug efficacy of human fibroblast-like synovial cells (FLS) via stable drug release in the extracellular environment and burst drug release under intracellular conditions.

Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System.

The plasma proteins around nanoparticles (NPs) form an outer protein corona, significantly influencing the subsequent immune response. However, it was uncertain whether the protein corona around NPs influences immune response. This study clarified that the immune response mediated by the protein corona is greatly dependent on the type of plasma proteins surrounding the NPs. Structural changes in the unfolded protein corona elevated reactive oxygen species (ROS) levels and induced major proinflammatory cytokine release in both murine and human macrophage cell lines. In contrast, negligible structural changes in the protein corona provoke neither ROS production nor proinflammatory cytokine release. Furthermore, in vivo analysis confirms that a stimulated immune response by an unfolded protein corona triggers selective activation of innate and adaptive immunity in the spleen. Specifically, neutrophils, natural killer cells, and CD8+ T cells are overpopulated by unfolded protein corona structures surrounding nanotubes, whereas innate and adaptive immunologic responses are not triggered by a normal protein corona. In conclusion, highly unfolded protein corona structures are strongly correlated with subsequent activation of proinflammatory cytokines and innate immune responses; thus, the protein corona can be used in immune-enhancing therapy.

Hispidulin alleviates 2,4-dinitrochlorobenzene and house dust mite extract-induced atopic dermatitis-like skin inflammation.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects 10-20% of the world's population. Therefore, the discovery of drugs for the treatment of AD is important for human health. Hispidulin (HPD; also known as scutellarein 6-methyl ether or dinatin) is a natural flavone that exerts anti-inflammatory effects. In the present study, the effectiveness of HPD on AD-like skin inflammation was investigated. We used a mouse AD model through repeated exposure of mice to 2,4-dinitrochlorobenzene and house dust mite extract (Dermatophagoides farinae extract, DFE) to the ears. In addition, tumor necrosis factor-α and interferon-γ-activated keratinocytes (HaCaT cells) were used to investigate the underlying mechanism of HPD action. Oral administration of HPD alleviated AD-like skin inflammations: it reduced ear thickness; serum immunoglobulin (Ig)E, DFE-specific IgE, and IgG2a levels; and inflammatory cell infiltration. HPD reduced the expression of pro-inflammatory cytokines and chemokines through inhibition of signal transducer and activator of transcription 1 nuclear factor-κB in HaCaT cells. Taken together, these results suggest that HPD could be a potential drug candidate for the treatment of AD.

Stem Cell Mimicking Nanoencapsulation for Targeting Arthritis.

Mesenchymal stem cells (MSCs) are considered a promising regenerative therapy due to their ability to migrate toward damaged tissues. The homing ability of MSCs is unique compared with that of non-migrating cells and MSCs are considered promising therapeutic vectors for targeting major cells in many pathophysiological sites. MSCs have many advantages in the treatment of malignant diseases, particularly rheumatoid arthritis (RA). RA is a representative autoimmune disease that primarily affects joints, and secreted chemokines in the joints are well recognized by MSCs following their migration to the joints. Furthermore, MSCs can regulate the inflammatory process and repair damaged cells in the joints. However, the functionality and migration ability of MSCs injected in vivo still show insufficient. The targeting ability and migration efficiency of MSCs can be enhanced by genetic engineering or modification, eg, overexpressing chemokine receptors or migration-related genes, thus maximizing their therapeutic effect. However, there are concerns about genetic changes due to the increased probability of oncogenesis resulting from genome integration of the viral vector, and thus, clinical application is limited. Furthermore, it is suspected that administering MSCs can promote tumor growth and metastasis in xenograft and orthotopic models. For this reason, MSC mimicking nanoencapsulations are an alternative strategy that does not involve using MSCs or bioengineered MSCs. MSC mimicking nanoencapsulations consist of MSC membrane-coated nanoparticles, MSC-derived exosomes and artificial ectosomes, and MSC membrane-fused liposomes with natural or genetically engineered MSC membranes. MSC mimicking nanoencapsulations not only retain the targeting ability of MSCs but also have many advantages in terms of targeted drug delivery. Specifically, MSC mimicking nanoencapsulations are capable of encapsulating drugs with various components, including chemotherapeutic agents, nucleic acids, and proteins. Furthermore, there are fewer concerns over safety issues on MSC mimicking nanoencapsulations associated with mutagenesis even when using genetically engineered MSCs, because MSC mimicking nanoencapsulations use only the membrane fraction of MSCs. Genetic engineering is a promising route in clinical settings, where nano-encapsulated technology strategies are combined. In this review, the mechanism underlying MSC homing and the advantages of MSC mimicking nanoencapsulations are discussed. In addition, genetic engineering of MSCs and MSC mimicking nanoencapsulation is described as a promising strategy for the treatment of immune-related diseases.

Potential Therapeutic Usage of Nanomedicine for Glaucoma Treatment.

Glaucoma is a group of diseases characterized by progressive degeneration of retinal ganglion cells, leading to irreversible blindness. Currently, intraocular pressure reduction is the only established treatment available for glaucoma. With this treatment, the progression of the disease can only be delayed and there is no recovery. In addition, the commercially available eye drops have the disadvantage of low compliance and short therapeutic time, while glaucoma surgery always has the risk of failure due to wound fibrosis. Nanotechnology can overcome the limitations of the current treatment through the encapsulation and conjugation of drugs used for lowering intraocular pressure and antifibrotic agents using biodegradable or biocompatible nanoparticles for the sustained release of the drugs to protect the damaged ocular cells. Furthermore, using nanotechnology, treatment can be administered in various forms, including eye drops, contact lens, and ocular inserts, according to the convenience of the patients. Despite the promising results of delaying the progression of glaucoma, the regeneration of damaged ocular cells, including trabecular meshwork and retinal ganglion cells, is another critical hurdle to overcome. Bone marrow-derived mesenchymal stem cells and Müller glia cells can secrete neurogenic factors that trigger the regeneration of associated cells, including trabecular meshwork and retinal ganglion cells. In conclusion, this review highlights the potential therapeutic applications of nanotechnology- and stem cell-based methods that can be employed for the protection and regeneration of ocular cells.

Past, Present, and Future of Anticancer Nanomedicine.

This review aims to summarize the methods that have been used till today, highlight methods that are currently being developed, and predict the future roadmap for anticancer therapy. In the beginning of this review, established approaches for anticancer therapy, such as conventional chemotherapy, hormonal therapy, monoclonal antibodies, and tyrosine kinase inhibitors are summarized. To counteract the side effects of conventional chemotherapy and to increase limited anticancer efficacy, nanodrug- and stem cell-based therapies have been introduced. However, current level of understanding and strategies of nanodrug and stem cell-based therapies have limitations that make them inadequate for clinical application. Subsequently, this manuscript reviews methods with fewer side effects compared to those of the methods mentioned above which are currently being investigated and are already being applied in the clinic. The newer strategies that are already being clinically applied include cancer immunotherapy, especially T cell-mediated therapy and immune checkpoint inhibitors, and strategies that are gaining attention include the manipulation of the tumor microenvironment or the activation of dendritic cells. Tumor-associated macrophage repolarization is another potential strategy for cancer immunotherapy, a method which activates macrophages to immunologically attack malignant cells. At the end of this review, we discuss combination therapies, which are the future of cancer treatment. Nanoparticle-based anticancer immunotherapies seem to be effective, in that they effectively use nanodrugs to elicit a greater immune response. The combination of these therapies with others, such as photothermal or tumor vaccine therapy, can result in a greater anticancer effect. Thus, the future of anticancer therapy aims to increase the effectiveness of therapy using various therapies in a synergistic combination rather than individually.