"Decoding inflammation: glycoprotein a repetition predominant, microRNA-142-3-p, and metastasis associated lung adenocarcinoma transcript 1: as novel inflammatory biomarkers of inflammatory bowel disease".

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.

Cytokine and chemokine profiles in women with endometriosis, polycystic ovary syndrome, and unexplained infertility.

Numerous factors (including immunological, congenital, hormonal, and morphological disorders) can lead to infertility. In this regard, 3 specific diseases associated with infertility are discussed in this review study (i.e., polycystic ovary syndrome [PCOS], endometriosis [EMS], and unexplained infertility [UI]). PCOS is a common endocrine disorder characterized by chronic low-grade inflammation, and EMS is a benign disease characterized by the presence of ectopic endometrial tissue. UI refers to couples who are unable to conceive for no known reason. Conception and pregnancy are significantly affected by the immune system; in this regard, chemokines and cytokines play important roles in the regulation of immune responses. Patients with PCOS, EMS, and UI have altered cytokine and chemokine profiles, suggesting that dysregulation of these molecules may contribute to infertility in these conditions. Accordingly, the issue of infertility is addressed in this review study, a condition that affects approximately 16% of couples worldwide.

Increased frequency of CD39+CD73+ regulatory T cells and Deltex-1 gene expression level in kidney transplant recipients with excellent long-term graft function.

BACKGROUND: The ability of regulatory T cells (Tregs) to limit inflammatory responses has been demonstrated. However, different subpopulations of this cell have varying abilities to suppress alloreactive immune responses. The primary goal of this study was to assess the frequency of CD4+FOXP3+CD39+CD73+ Tregs and Deltex-1 gene expression on long-term renal transplant function. METHODS: A total of 49 subjects were divided into 3 groups: (i) the excellent long-term graft function (ELTGF) group, (ii) the chronic graft dysfunction (CGD) group, and (iii) the healthy control (HC) group. Following sample collection, peripheral blood mononuclear cells (PBMCs) were isolated, and the Deltex-1 gene expression level and the frequency of CD4+FOXP3+CD39+CD73+ Tregs were evaluated. RESULTS: The ELTGF group had more CD4+FOXP3+ Tregs than the CGD group, but the difference was not statistically significant (P = 0.07). However, the frequency of CD4+FOXP3+CD39+CD73+ Tregs and the ratio of these cells to total CD4+ lymphocytes significantly increased in the ELTGF group than in the CGD group (P = 0.04 and P = 0.02 respectively). In addition, the expression level of the Deltex-1 gene was significantly lower in the CGD group than in the other 2 groups (P = 0.01 and P = 0.04 respectively). CONCLUSIONS: Given the increased frequency of CD4+FOXP3+CD39+CD73+ Tregs and the expression level of the Deltex-1 gene in the ELTGF group, it appears that these factors probably improved function and long-term survival of the transplanted organ through the suppression of alloreactive responses and reduction of inflammation. In other words, one of the immunological mechanisms involved in the CGD group may be a deficiency in Tregs.

Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: Evidence about the development of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an aggressive disease characterized by central nervous system (CNS) inflammatory and demyelinating lesions. Tolerance failure is implicated in the development of several autoimmune disorders, including MS. Due to their involvement in maintaining environmental tolerance, regulatory T cells (Tregs) are regarded as efficient immune cells. We examined the frequency of Tregs in this study using CD4/CD25/forkhead box protein P3 (FOXP3)/Helios markers. METHODS: Fifty participants, including 25 patients with secondary progressive MS (SPMS) and 25 healthy controls (HCs), were enrolled in this study, and their demographic characteristics were recorded. Peripheral blood samples ranging from 5 to 6 mL were obtained, and the Ficoll technique was used to extract peripheral blood mononuclear cells (PBMCs). Then, the percentage of CD4+CD25+FOXP3+Helios+ regulatory T lymphocytes was examined by flow cytometry in the study groups. Real-time polymerase chain reaction (PCR) was also used to assess the Helios gene expression level. RESULTS: This study showed that the percentage of Tregs with CD4 and CD25 markers did not reveal a significant difference compared with HCs despite the decrease in SPMS patients (P = 0.6). However, lymphocytes with CD4/CD25/FOXP3/Helios markers were significantly reduced in the patients (P = 0.01). Additionally, SPMS patients had statistically significantly lower Helios gene expression levels (P = 0.002). CONCLUSION: In SPMS patients, a decrease in the frequency of the CD4+CD25+FOXP3+Helios+ Treg population can result in an imbalanced immune system. In other words, one of the immunological mechanisms involved in this disease may be a deficiency in Tregs. Helios gene expression was also decreased in these patients, which may exacerbate functional defects in Tregs.

Inhibition of Exosome Release Sensitizes U937 Cells to PEGylated Liposomal Doxorubicin.

Aims: Acute myeloblastic leukemia (AML) is the most common type of acute leukemia in adults. Despite numerous treatment strategies including chemotherapy and radiotherapy, a large number of patients do not respond to treatment and experience relapse. The main problem of these patients is the development of resistance to anti-cancer drugs. Therefore, any endeavor to reduce drug resistance in these patients is of high priority. In general, several mechanisms such as changes in drug metabolic pathways, drug inactivation, drug target alterations and reduced drug accumulation in the cells contribute to drug resistance of cancer cells. In this context, evidence suggests that exosomes could reduce drug resistance by removing drugs from their parent cells. In the present study, we aimed to investigate the effects of exosome release inhibition on the resistance of U937 cells to PEGylated liposomal doxorubicin (PLD). Main Methods: In order to find a suitable ABCG2 (ATP-binding cassette sub-family G member 2) transporter substrate, virtual screening was performed among a list of drugs used in leukemia and PLD was selected. U937 cells were treated with PLD with/without co-treatment with the exosome release inhibitor, GW4869. Released exosomes within different study groups were isolated and characterized to determine the differences between groups. Doxorubicin presence in the isolated exosomes was also measured by high performance liquid chromatography (HPLC) to confirm drug export through the exosomes. Finally, the effect of exosome inhibition on the cytotoxicity of PLD on U937 cells was determined using different cytotoxicity assays including the standard lactate dehydrogenase (LDH) release assay and the flow cytometric analysis of apoptotic and non-apoptotic cell death. Key Findings: GW4869 treatment caused a significant decrease in the exosome release of U937 cells compared to the untreated cells, as evidenced by the reduction of the protein content of the isolated exosomes (P<0.05). Co-treatment with GW4869 significantly increased cytotoxic cell death in the groups treated with 0.5 and 1 µM PLD, compared to the same groups without GW4869 co-treatment (P<0.05). Interestingly, co-treatment with GW4896 and 0.5 µM PLD was enough to induce the same cytotoxic effect as that of the sole 1 µM PLD group. Significance: Our findings showed that U937 cells increase their resistance against the cytotoxic effects of PLD through the exosome-mediated expelling of the drug. Inhibition of exosome release could prevent PLD efflux and consequently increase the vulnerability of the U937 cells to the cytotoxic effects of PLD. Our results along with prior studies indicate that the integration of exosome release inhibitors into the common PLD-containing chemotherapy regimens could significantly lower the required concentrations of the drug and consequently reduce its associated side effects. Further studies are warranted to identify clinically safe inhibitors and investigate their clinical efficacy.

Pronounce expression of Tim-3 and CD39 but not PD1 defines CD8 T cells in critical Covid-19 patients.

BACKGROUND: During viral infection, inhibitory receptors play a key role in regulating CD8 T-cell activity. The objective of this research was to investigate programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), and CD39 exhaustion markers in CD8 T cells of new coronavirus disease-2019 (COVID-19) patients. METHODS: A total of 44 patients with COVID-19 (17 subjects in a critical group and 27 patients in a non-critical group) and 14 healthy controls, who were admitted to Hospitals in Babol, were recruited to the study. In subjects' peripheral blood mononuclear cells (PBMCs), we compared the phenotype of CD8 T lymphocytes, expressing PD-1, TIM-3, or CD39, both alone and in various combinations. RESULTS: The findings showed that the percentage of CD8+ cells was significantly lower in patients. Critical and non-critical patients were more likely than healthy controls to have an escalated frequency of CD8+ TIM-3+, CD8+ CD39+, and CD8+ TIM-3+ CD39+ cells. No significant differences were observed between all groups in the CD8+ PD-1+ cell counts. There was also no difference between three groups regarding the counts of CD8+ TIM-3+ PD-1+, CD8+ PD-1+ CD39+, and CD8+ TIM-3+ PD-1+ CD39+ cells. The counts of non-exhausted cells were significantly lower in critical and non-critical individuals compared to the healthy individuals' value. CONCLUSION: Patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered exhausted CD8 T lymphocytes with CD39 and TIM-3 exhaustion markers, which may account the dysregulated immune response found in COVID-19.

Decreased Frequency of CD8+HLA-G+ T Cell in the Peripheral Blood of Primary Unexplained Infertile Females.

Most of the findings have focused on the importance of CD4+HLA-G+ and CD8+HLA-G+ regulatory T cells (Treg) during pregnancy. It has been demonstrated that these HLA-G+ T cell subsets could induce maternal immune tolerance against semi-allogenic conceptus during pregnancy. There are only a few experiments regarding the Treg cells in the context of unexplained infertility (UI). Thirty-five participants including 18 primary unexplained infertile and 17 fertile females were enrolled in this study. A total of 3-5 ml blood samples were taken, and peripheral blood mononuclear cells (PBMCs) were separated by using Ficoll. Using a flow cytometer, the frequency of CD4+HLA-G+ and CD8+ HLA-G+ T cells was assessed in the peripheral blood samples of primary unexplained infertile and fertile females. Our results showed that the frequency of CD8+HLA-G+ Treg cells was significantly lower in primary unexplained infertile females than fertile females (P = 0.048). Although the frequency of CD4+HLA-G+ Treg cells in the primary unexplained infertile females was lower than fertile females, the difference was not statistically significant (P = 0.25). Regarding the important role of CD8+HLA-G+ Treg cells during pregnancy and its decrease in females with primary UI, it seems that reduced CD8+ HLA-G+ Treg cells could be a leading immunological factor in the context of infertility. Nevertheless, more researches are needed in this field.

Under-expression of microRNA-146a and 21 and their association with Crohn's disease.

MicroRNAs (miRNAs) can post-transcriptionally regulate gene expression and are involved in the immune response. Excessive immune response to the gut microbiota plays a major role in the pathogenesis of Crohn's disease (CD). Regarding the role of miRNAs in immune response, this study aimed to investigate the contribution of miRNAs in the pathogenesis of CD. A total of 53 participants, including 23 CD patients and 30 healthy controls (HCs) were enrolled in this study. miRNAs, including miR-21, miR-29a, miR-29b, miR-31, miR-146a, miR-155, miR-181a, and miR-181c were evaluated via TaqMan MicroRNA Assays. Among the eight miRNAs, the amounts of miR-146a and miR-21 were significantly decreased in the CD patients relative to HC subjects. Moreover, we showed that there was a negative correlation between miR-146a and Harvey-Bradshaw index (HBI), as well as a positive correlation of miR-21 and miR-29b with HBI. Under-expression of miR-146a and miR-21, which are critical for the regulatory function of regulatory T cells (Tregs), is remarkably associated with CD.

Soluble CD30, the Immune Response, and Acute Rejection in Human Kidney Transplantation: A Systematic Review and Meta-Analysis.

Soluble CD30 (sCD30) is considered to be a marker for the activated immune system in which T cells can damage the allograft. Some studies reported that post-transplant sCD30 can predict early acute rejection and can thereby be used as a biomarker to detect acute rejection. However, several other studies found no relation between post-transplant sCD30 and acute rejection. This meta-analysis study aims to answer this main question of whether sCD30 can help clinicians to monitor transplant recipients. The electronic databases, including PubMed, Web of Science, ProQuest, Embase, Scopus, Google Scholar, the gray literature, and the key journals, were searched for observational studies from 1 January 1990 up to 30 April 2018. Eighteen studies, with a total of 1,453 patients, were included in this paper. With regard to the different measurement times, post-transplant sCD30 was separately analyzed and divided into five groups (i.e., 1, 2, 3, 4 week, and 1 month post-transplant sCD30). All groups indicated a strong association between sCD30 and the acute rejection. The standardized mean difference (SMD) is 1.22 in 1 week, 0.77 in 2 week, 1.11 in 3 week, 1.27 in 4 week, and 0.71 in 1 month groups. The association between sCD30 and acute rejection was consistent across all the subgroup analyses. We found that post-transplant sCD30 had a strong association with acute kidney rejection. We also found that the deceased donors had more association with the high amount of sCD30 than living donors in patients with acute rejection. Finally, we realized that donor type was an important factor leading to the heterogeneous results in the primary studies.

The exosome as a novel predictive/diagnostic biomarker of rejection in the field of transplantation.

Finding a non-invasive biomarker to monitor allograft status after transplantation could contribute to better control of the post-transplant status of transplant recipients and, if possible, could be used instead of invasive biopsy for proving rejection. On the other hand, reducing the dosage of immunosuppression or stopping lifelong use of them because of their severe side effects is an important goal in order to dispose of their severe side effects. The ability of exosomes as a biomarker of rejection and as a therapeutic strategy was investigated in the human kidney, heart, and lung transplantation or in transplantation models with interesting results. Moreover, the ability of exosome was assessed as antigen-presenting vesicles (APVs), in which exosomes can either participate in immune stimulation (semi-direct recognition) or immune suppression thereby, influence on the transplantation outcome. In this paper, authors try to provide comprehensive information about triple role of exosomes in the transplantation medicine.

TIM-3 as a marker of exhaustion in CD8+ T cells of active chronic hepatitis B patients.

BACKGROUND: Chronic HBV infection presents weak or no virus-specific T-cell responses, implying to an exhausted phenotype, characterized by overexpression of several inhibitory receptors. In the present study, it was aimed to characterize the panel of inhibitory molecules on the CD8+ T cells in patients with active chronic HBV infection. METHODS: In this study, 31 active and 32 inactive individuals with chronic HBV infection were recruited. Peripheral blood mononuclear cells were isolated and a multicolor flow cytometry was applied to evaluate the surface inhibitory molecules of TIM3, PD-1, and CD39. RESULTS: CD8+ T cells expressing TIM3 were significantly higher in cases with active chronic HBV infection compared to inactive chronic HBV group (8.43 ±â€¯1.4 vs. 5.15 ±â€¯1.43; P < 0.0001). CD8+TIM3+PD-1+ T cells were significantly higher in active chronic HBV cases in comparison to the inactive chronic HBV subjects (4.26 ±â€¯1.04 vs. 3.41 ±â€¯0.74; P < 0.001). Different subpopulations of the CD8+ T cells were correlated with the duration of infection and HBV DNA load in the cases with active chronic HBV infection. CONCLUSION: It appears that CD8+ TIM3+ T cells are the major exhausted phenotype of T cells during the active state of HBV infection.

Diagnostic methods for Helicobacter pylori infection: ideals, options, and limitations.

Helicobacter pylori (H. pylori) resides in the stomach, colonizes gastric epithelium, and causes several digestive system diseases. Several diagnostic methods utilizing invasive or non-invasive techniques with varying levels of sensitivity and specificity are developed to detect H. pylori infection. Selection of one or more diagnostic tests will depend on the clinical conditions, the experience of the clinician, cost, sensitivity, and specificity. Invasive methods require endoscopy with biopsies of gastric tissues for the histology, culture, and rapid urease test. Among non-invasive tests, urea breath test and fecal antigen tests are a quick diagnostic procedure with comparable accuracy to biopsy-based techniques and are methods of choice in the test and treatment setting. Other techniques such as serological methods to detect immunoglobulin G antibodies to H. pylori can show high accuracy as other non-invasive and invasive biopsies, but do not differentiate between current or past H. pylori infections. Polymerase chain reaction (PCR) is an emerging option that can be categorized as invasive and non-invasive tests. PCR method is beneficial to detect H. pylori from gastric biopsies without the need for the cultures. There is no other chronic gastrointestinal infection such as H. pylori with a set of comparable diagnostic methodologies. Despite the availability of multiple diagnostic methods, it remains unclear on the choice of any one method as the gold standard for detecting H. pylori infection, especially in epidemiological studies. In this work, we review the principal diagnostic methods used to detect H. pylori infection and their advantages and disadvantages, and applications in clinical practice.

Human PBMCs fight or flight response to starvation stress: Increased T-reg, FOXP3, and TGF-ß1 with decreased miR-21 and Constant miR-181c levels.

Regulatory T-lymphocytes play a prominent role in autoimmunity, allergy, and cancer. In some conditions such as inflammation and tumor, immune cells are encountered with metabolic stress. Emerging evidence indicates the contribution of microRNAs in both metabolism and immune regulation. Herewith, we have examined the in vitro effects of serum starvation for 16, 48, 72 and 96 h on the expression of T-reg differentiation markers (CD4, CD25, CD127, and FOXP3) as well as on the Transforming Growth Factor-ß1 (TGF-ß1) and some microRNAs (miR-21,-29a,-31,146a,-155,-181a and -181c) levels in human Peripheral Blood Mononuclear Cells (PBMCs). The percentage of CD4+CD25+CD127low/-FOXP3+ T-regs, as well as FOXP3 expression, was increased in starved lymphocytes (p < 0.01). 96 h-starved PBMCs had the lowest T-eff/T-reg ratio (p < 0.05). All the studied miRNAs except miR-181c were significantly down-regulated in those cells (p < 0.05), in particular, miR-29a and miR-155 were sharply declined in 48h-starved PBMCs (p < 0.01). There was a negative correlation between time of starvation and microRNAs expression, except for miR-181c (r-value = -0. 61 to -0.9 and p-value = 0.037 to 0). The percentage of T-reg was inversely correlated with all miRNAs levels except for miR-31 and miR-181c (r-value = -0.68 to -0.78 and p-value = 0.015 to 0.003). FOXP3 expression exhibited a same degree of negative correlation with miR-31 and miR-155 expression levels (r = -0.57 and p = 0.05, for both). Increasing starvation duration led to a rise inTGF-ß1 protein levels (p<0.01), especially its active form (P<0.001). This study introduced the serum starvation as a tool for immunoregulation which acts probably through increasing TGF-ß1 production and inducing some alterations in microRNAs expression.

T cell exhaustion implications during transplantation.

Exhaustion of lymphocyte function, particularly T cell exhaustion, due to prolonged exposure to a high load of foreign antigen is commonly seen during chronic viral infection as well as antitumor immune responses. This phenomenon has been associated with a determined molecular mechanism and phenotypic manifestations on the cell surface. In spite of investigation of exhaustion, mostly about CD8 responses toward viral infections, recent studies have reported that chronic exposure to antigen may develop exhaustion in CD4 + T cells, B cells, and NK cells. Little is known with respect to lymphocyte exhaustion during transplantation and its effect on aberrant anti-graft responses. Through a same mechanobiology observed during chronic exposure of foreign viral antigens, alloantigen persistence mediated by allograft could develop a favorable circumstance for exhaustion of T cells responding to allograft. However, to achieve better manipulation approaches of this event to reduce the complications during transplantation, we need to be armed with a bulk of knowledge with regard to quality and quantity of T cell exhaustion occurring in various allografts, the kinetics of exhaustion development, the impression of immunosuppressive agents on the exhaustion, and the influence of exhaustion on graft survival and immune tolerance.

The effect of transplanted human Wharton's jelly mesenchymal stem cells treated with IFN-γ on experimental autoimmune encephalomyelitis mice.

Interferon gamma (IFN-γ) increases the immunosuppressive property of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs). In this study, we evaluated the therapeutic effects of IFN-γ primed WJ-MSCs in EAE mice. IFN-γ primed WJ-MSCs were injected on days 3 and 11 after EAE induction. 21 days after EAE induction, splenocytes and cervical lymph node cells were isolated and cell proliferation, secretion of inflammatory cytokines and frequency of regulatory T-cells was measured. On day 50 of the study, cell infiltration and gene expression of inflammatory cytokines in brain of mice were studied. Leukocyte infiltration and symptoms were significantly reduced in IFN-γ primed WJ-MSCs treated group compared to other groups. These cells showed significantly reduced proliferation and increased Treg cells as well as decreased secretion and gene expression of inflammatory cytokines in EAE mice. Our data suggest that IFN-γ may be used to stimulate the immunomodulatory property of WJ-MSCs in clinical situations.

Application of nanomedicine for crossing the blood-brain barrier: Theranostic opportunities in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized with immunopathobiological events, including lymphocytic infiltration into the central nervous system (CNS), microglia activation, demyelination and axonal degeneration. Although several neuroprotective drugs have been designed for the treatment of MS, complete remission is yet matter of debate. Therefore, development of novel therapeutic approaches for MS is of a high priority in immunological research. Nanomedicine is a recently developed novel medical field, which is applicable in both diagnosis and treatment of several cancers and autoimmune diseases. Although there is a marked progress in neuroimaging through using nanoparticles, little is known regarding the therapeutic potential of nanomedicine in neurological disorders, particularly MS. Moreover, the majority of data is limited to the MS related animal models. In this review, we will discuss about the brain targeting potential of different nanoparticles as well as the role of nanomedicine in the diagnosis and treatment of MS and its animal model, experimental autoimmune encephalomyelitis.

Myeloid-derived suppressor cells in B cell malignancies.

Tumor cells use several mechanisms such as soluble immune modulators or suppressive immune cells to evade from anti-tumor responses. Immunomodulatory cytokines, such as transforming growth factor-ß, interleukin (IL)-10, and IL-35, soluble factors, such as adenosine, immunosuppressive cells, such as regulatory T cells, NKT cells and myeloid-derived suppressor cells (MDSCs), are the main orchestra leaders involved in immune suppression in cancer by which tumor cells can freely expand without immune cell-mediated interference. Among them, MDSCs have attracted much attention as they represent a heterogenous population derived from myeloid progenitors that are expanded in tumor condition and can also shift toward other myeloid cells, such as macrophages and dendritic cells, after tumor clearing. MDSCs exert their immunosuppressive effects through various immune and non-immune mechanisms which make them as potent tumor-promoting cells. Although, there are several studies regarding the immunobiology of MDSCs in different solid tumors, little is known about the precise characteristics of these cells in hematological malignancies, particularly B cell malignancies. In this review, we tried to clarify the precise role of MDSCs in B cell-derived malignancies.

Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy.

The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy.