Preparation and in vitro evaluation of cell adhesion and long-term proliferation of stem cells cultured on silibinin co-embedded PLGA/Collagen electrospun composite nanofibers.

The present research aims to evaluate the efficacy of Silibinin-loaded mesoporous silica nanoparticles (Sil@MSNs) immobilized into polylactic-co-glycolic acid/Collagen (PLGA/Col) nanofibers on the in vitro proliferation of adipose-derived stem cells (ASCs) and cellular senescence. Here, the fabricated electrospun PLGA/Col composite scaffolds were coated with Sil@MSNs and their physicochemical properties were examined by FTIR, FE-SEM, and TGA. The growth, viability and proliferation of ASCs were investigated using various biological assays including PicoGreen, MTT, and RT-PCR after 21 days. The proliferation and adhesion of ASCs were supported by the biological and mechanical characteristics of the Sil@MSNs PLGA/Col composite scaffolds, according to FE- SEM. PicoGreen and cytotoxicity analysis showed an increase in the rate of proliferation and metabolic activity of hADSCs after 14 and 21 days, confirming the initial and controlled release of Sil from nanofibers. Gene expression analysis further confirmed the increased expression of stemness markers as well as hTERT and telomerase in ASCs seeded on Sil@MSNs PLGA/Col nanofibers compared to the control group. Ultimately, the findings of the present study introduced Sil@MSNs PLGA/Col composite scaffolds as an efficient platform for long-term proliferation of ASCs in tissue engineering.

Fabrication of magnetic niosomal platform for delivery of resveratrol: potential anticancer activity against human pancreatic cancer Capan-1 cell.

Recently, the presence of different nanoparticles (NPs) has developed targeting drug delivery in treatment of cancer cell. Targeted drug delivery systems using NPs have shown great promise in improving the efficacy of intracellular uptake as well as local concentration of therapeutics with minimizing side effects. The current study planned to synthesized resveratrol-loaded magnetic niosomes nanoparticles (RSV-MNIONPs) and evaluate their cytotoxicity activity in pancreatic cancer cells. For this aim, magnetic nanoparticles (MNPs) were synthesized and loaded into niosomes (NIOs) by the thin film hydration technique and then characterized via DLS, FT-IR, TEM, SEM and VSM techniques. Moreover, the cytotoxic activity of the RSV-MNIONPs on the Capan-1 cells line was assessed by the MTT test. The distribution number of RSV-MNIONPs was gained about 80 nm and 95 nm with surface charge of - 14.0 mV by SEM and TEM analysis, respectively. RSV loading efficacy in NIOs was about 85%, and the drug releases pattern displayed a sustained discharge with a maximum amount about 35% and 40%, within 4 h in pH = 7.4 and pH = 5.8, respectively. The cytotoxicity of the RSV-MNIONPs in the presence of an external magnetic field is higher than that of the RSV, indicating enhanced cellular uptake in their encapsulated states. Furthermore, RSV loaded MNNPs were found to induce more cell cycle arrest at the G0/G1 checkpoint than free RSV. Compared with RSV-treated cells, the mRNA expression levels of BAX, Bcl2, FAS, P 53, Cyclin D and hTERT, were significantly changed in cells treated with RSV loaded MNNPs. The niosomes NPs approaches have been widely used to attain higher solubility, improved bioavailability, enhanced stability, and control delivery of RSV. Our formulation displayed antitumor activity and can be considered an appropriate carrier with a great potential for future usage in cancer therapy.

Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents.

Cancer is a major public health problem worldwide with more than an estimated 19.3 million new cases in 2020. The occurrence rises dramatically with age, and the overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less effective in older individuals. Conventional cancer treatments, such as radiotherapy, surgery, and chemotherapy, have been used for decades to combat cancer. However, the emergence of novel fields of cancer research has led to the exploration of innovative treatment approaches focused on immunotherapy, epigenetic therapy, targeted therapy, multi-omics, and also multi-target therapy. The hypothesis was based on that drugs designed to act against individual targets cannot usually battle multigenic diseases like cancer. Multi-target therapies, either in combination or sequential order, have been recommended to combat acquired and intrinsic resistance to anti-cancer treatments. Several studies focused on multi-targeting treatments due to their advantages include; overcoming clonal heterogeneity, lower risk of multi-drug resistance (MDR), decreased drug toxicity, and thereby lower side effects. In this study, we'll discuss about multi-target drugs, their benefits in improving cancer treatments, and recent advances in the field of multi-targeted drugs. Also, we will study the research that performed clinical trials using multi-target therapeutic agents for cancer treatment.

A State-of-the-Art Review on the Recent Advances of Mesenchymal Stem Cell Therapeutic Application in Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that has widespread clinical and immunological manifestations. Despite the increase in knowledge about the pathogenesis process and the increase in treatment options, however, the treatments fail in half of the cases. Therefore, there is still a need for research on new therapies. Mesenchymal stem cells (MSCs) are powerful regulators of the immune system and can reduce the symptoms of systemic lupus erythematosus. This study aimed to review the mechanisms of immune system modulation by MSCs and the role of these cells in the treatment of SLE. MSCs suppress T lymphocytes through various mechanisms, including the production of transforming growth factor-beta (TGF-B), prostaglandin E2 (PGE2), nitric oxide (NO), and indolamine 2 and 3-oxygenase (IDO). In addition, MSCs inhibit the production of their autoantibodies by inhibiting the differentiation of lymphocytes. The production of autoantibodies against nuclear antigens is an important feature of SLE. On the other hand, MSCs inhibit antigen delivery by antigen-presenting cells (APCs) to T lymphocytes. Studies in animal models have shown the effectiveness of these cells in treating SLE. However, few studies have been performed on the effectiveness of this treatment in humans. It can be expected that new treatment strategies for SLE will be introduced in the future, given the promising results of MSCs application.

Protective effect of melatonin against methamphetamine-induced attention deficits through miR-181/SIRT1 axis in the prefrontal cortex.

INTRODUCTION: Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition, attention and executive functions, but the underlying mechanisms are still unclear. Sirtuin 1 (SIRT1) is a post-translational regulator that is downregulated following METH neurotoxicity. Melatonin is a neuroprotective hormone that enhances mitochondrial metabolism. Here, we evaluated the effect of melatonin on METH-induced attention deficits disorder and the involvement of the miR-181/SIRT1 axis in melatonin neuroprotection. METHODS AND RESULTS: METH at a dose of 5 mg/kg was injected for 21 consecutive days. The animals were assigned to receive either melatonin or the vehicle after METH injections. Attention levels were evaluated with abject-based attention test. In the prefrontal cortex, the expression levels of miR-181a-5p, SIRT1, p53 and CCAR2, as well as the mtDNA copy numbers were evaluated using qRT-PCR and western blotting. The outcomes revealed that melatonin treatment following METH injections improved METH-induced attention deficits. METH toxicity can be associated with changes in the miR-181/SIRT1 axis, elevated levels of p53 and COXII, and decreased levels of mtDNA in the prefrontal cortex of adult rats. Interestingly, administration of melatonin can improve the expression of these molecules and reduces the toxic effects of METH. CONCLUSION: Melatonin ameliorated the neurotoxicity of METH in the prefrontal cortex and the miR-181/SIRT1 axis is involve in the protective effects of melatonin. However, melatonin can be potentially administrated to improve attention impairment in METH use disorders.

Fabrication and characterization of metformin-loaded PLGA/Collagen nanofibers for modulation of macrophage polarization for tissue engineering and regenerative medicine.

In tissue engineering (TE) and regenerative medicine, the accessibility of engineered scaffolds that modulate inflammatory states is extremely necessary. The aim of the current work was to assess the efficacy of metformin (MET) incorporated in PLGA/Collagen nanofibers (Met-PLGA/Col NFs) to modulate RAW264.7 macrophage phenotype from pro-inflammatory status (M1) to anti-inflammatory status (M2). Given this, MET-PLGA/Col NFs were fabricated using an electrospinning technique. Structural characterization such as morphology, chemical and mechanical properties, and drug discharge pattern were assessed. MTT assay test exposed that MET-PLGA/Col NFs remarkably had increased cell survival in comparison with pure PLGA/Collagen NFs and control (p < 0.05) 72 h after incubation. Based on the qPCR assay, a reduction in the expression of iNOS-2 and SOCS3 was found in the cells seeded on MET-PLGA/Col NFs, demonstrating the substantial modulation of the M1 phenotype to the M2 phenotype. Moreover, it was determined a main decrease in the pro-inflammatory cytokines and mediator's expression but the growth factors amount related to anti-inflammatory M2 were meaningfully upregulated. Finally, MET-PLGA/Col NFs possibly will ensure a beneficial potential for effective variation of the macrophage response from an inflammatory phase (M1) to a pro-regenerative (M2) phase.

Preparation and characterization of propolis reinforced eggshell membrane/ GelMA composite hydrogel for biomedical applications.

Gelatin methacrylate-based hydrogels (GelMA) were widely used in tissue engineering and regenerative medicine. However, to manipulate their various chemical and physical properties and create high-efficiency hydrogels, different materials have been used in their structure. Eggshell membrane (ESM) and propolis are two nature-derived materials that could be used to improve the various characteristics of hydrogels, especially structural and biological properties. Hence, the main purpose of this study is the development of a new type of GelMA hydrogel containing ESM and propolis, for use in regenerative medicine. In this regard, in this study, after synthesizing GelMA, the fragmented ESM fibers were added to it and the GM/EMF hydrogel was made using a photoinitiator and visible light irradiation. Finally, GM/EMF/P hydrogels were prepared by incubating GM/EMF hydrogels in the propolis solution for 24 h. After various structural, chemical, and biological characterizations, it was found that the hydrogels obtained in this study offer improved morphological, hydrophilic, thermal, mechanical, and biological properties. The developed GM/EMF/P hydrogel presented more porosity with smaller and interconnected pores compared to the other hydrogels. GM/EMF hydrogels due to possessing EMF showed compressive strength up to 25.95 ± 1.69 KPa, which is more than the compressive strength provided by GM hydrogels (24.550 ± 4.3 KPa). Also, GM/EMF/P hydrogel offered the best compressive strength (44.65 ± 3.48) due to the presence of both EMF and propolis. GM scaffold with a contact angle of about 65.41 ± 2.199 θ showed more hydrophobicity compared to GM/EMF (28.67 ± 1.58 θ), and GM/EMF/P (26.24 ± 0.73 θ) hydrogels. Also, the higher swelling percentage of GM/EMF/P hydrogels (343.197 ± 42.79) indicated the high capacity of this hydrogel to retain more water than other scaffolds. Regarding the biocompatibility of the fabricated structures, MTT assay results showed that GM/EMF/P hydrogel significantly (p-value < 0.05) supported cell viability. Based on the results, it seems that GM/EMF/P hydrogel could be a promising biomaterial candidate for use in various fields of regenerative medicine.

The role of non-coding RNAs in the diagnosis of different stages (HCC, CHB, OBI) of hepatitis B infection.

Despite the availability of an effective hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV has remained a health problem in various stages such as occult hepatitis B infection (OBI), chronic hepatitis B (CHB), and hepatocellular carcinoma (HCC), which is considered one of the possible phases during chronic HBV infection. OBI is defined as the persistence of HBV genomes in hepatocytes of patients with a negative HBV surface antigen (HBsAg) test and detectable or undetectable HBV DNA in the blood. OBI is occasionally associated with infection caused by mutant viruses that produce a modified HBsAg that is undetected by diagnostic procedures or with replication-defective variations. Many aspects of HBV (OBI more than any other stage) including prevalence, pathobiology, and clinical implications has remained controversial. According to a growing body of research, non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been linked to the development and progression of a number of illnesses, including viral infectious disorders. Despite a shortage of knowledge regarding the expression and biological activities of lncRNAs and miRNAs in HBV infection, Hepatitis B remains a major global public health concern. This review summarizes the role of lncRNAs in the diagnosis and treatment of different stages of hepatitis B infection.

Recent advances in the detection of glioblastoma, from imaging-based methods to proteomics and biosensors: A narrative review.

Glioblastoma (GBM) is an aggressive type of cancer that originates in the cells called astrocytes, which support the functioning of nerve cells. It can develop in either the brain or the spinal cord and is also known as glioblastoma multiform. GBM is a highly aggressive cancer that can occur in either the brain or spinal cord. The detection of GBM in biofluids offers potential advantages over current methods for diagnosing and treatment monitoring of glial tumors. Biofluid-based detection of GBM focuses on identifying tumor-specific biomarkers in blood and cerebrospinal fluid. To date, different methods have been used to detect biomarkers of GBM, ranging from various imaging techniques to molecular approaches. Each method has its own strengths and weaknesses. The present review aims to scrutinize multiple diagnostic methods for GBM, with a focus on proteomics methods and biosensors. In other words, this study aims to provide an overview of the most significant research findings based on proteomics and biosensors for the diagnosis of GBM.

Potentiation of Folate-Functionalized PLGA-PEG nanoparticles loaded with metformin for the treatment of breast Cancer: possible clinical application.

AIM: Folate receptor expression increase up to 30% in breast cancer cells and could be used as a possible ligand to couple to folate-functionalized nanoparticles. Metformin (Met) is an anti-hyperglycemic agent whose anti-cancer properties have been formerly reported. Consequently, in the current study, we aimed to synthesize and characterize folate-functionalized PLGA-PEG NPs loaded with Met and evaluate the anti-cancer effect against the MDA-MB-231 human breast cancer cell line. METHODS: FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes. RESULT: MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs. CONCLUSION: Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.

Recent advances in treatment Crimean-Congo hemorrhagic fever virus: A concise overview.

The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is widespread in Africa, Asia, and Europe, among other places. The disease was initially discovered in the Crimean cities of the Soviet Union and the Congo, and it was given the name Crimean Congo because it induces hemorrhagic fever. According to studies, when the virus enters the body, it settles in immune cells such as macrophages and dendritic cells, causing them to malfunction and secrete inflammatory cytokines such as TNF-alpha, IL1, and IL6, resulting in cytokine storms that induces shock via endothelial activation and vascular leakage, while on the other hand, clots and disseminated intravascular coagulation (DIC) formation causes massive defects in various organs such as the liver and kidneys, as well as fatal bleeding. Disease prevention and treatment are crucial since no other effective vaccination against the disease has yet been developed. Immunotherapy is utilized as a consequence. One of the most effective treatments, when combined with compensatory therapies such as blood and platelet replacement, water, electrolytes, Fresh Frozen Plasma (FFP) replacement, and other compensatory therapies, is one of the most effective treatments. Studies; show that immunotherapy using IVIG and neutralizing and non-neutralizing monoclonal antibodies; cytokine therapy, and anti-inflammatory therapy using corticosteroids are effective ways to treat the disease.

Recent advances in targeted drug delivery systems for resistant colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.

An update of Nrf2 activators and inhibitors in cancer prevention/promotion.

NF-E2-related factor 2 (Nrf2) protein is a basic-region leucine zipper transcription factor that defends against endogenous or exogenous stressors. By inducing several cytoprotective and detoxifying gene expressions, Nrf2 can increase the sensitivity of the cells to oxidants and electrophiles. Transient Nrf2 activation, by its specific activators, has protective roles against carcinogenesis and cancer development. However, permanent activation of Nrf2 promotes various cancer properties, comprising malignant progression, chemo/radio resistance, and poor patient prognosis. Taken together, these findings suggest that reaching an optimal balance between paradoxical functions of Nrf2 in malignancy may render a selective improvement to identify therapeutic strategies in cancer treatment. In this review, we describe lately discovered Nrf2 inducers and inhibitors, and their chemopreventive and/or anticancer activities.

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.

An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to COVID-19 and has become a pandemic worldwide with mortality of millions. Nanotechnology can be used to deliver antiviral medicines or other types of viral reproduction-inhibiting medications. At various steps of viral infection, nanotechnology could suggest practical solutions for usage in the fight against viral infection. Nanotechnology-based approaches can help in the fight against SARS-CoV-2 infection. Nanoparticles can play an essential role in progressing SARS-CoV-2 treatment and vaccine production in efficacy and safety. Nanocarriers have increased the speed of vaccine development and the efficiency of vaccines. As a result, the increased investigation into nanoparticles as nano-delivery systems and nanotherapeutics in viral infection, and the development of new and effective methods are essential for inhibiting SARS-CoV-2 infection. In this article, we compare the attributes of several nanoparticles and evaluate their capability to create novel vaccines and treatment methods against different types of viral diseases, especially the SARS-CoV-2 disease.

Gastrointestinal Tract, Microbiota and Multiple Sclerosis (MS) and the Link Between Gut Microbiota and CNS.

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe neurological defects. Evidence is mounting that immune function is crucial in neuroinflammatory illnesses like MS. Through its impact on systemic immunological reactions, the large microbial population known as the gut microbiota has been linked to both human health and disease. The gut-brain axis (GBA) therefore encompasses neurological, immunological, and hormonal pathways, and microbiota can have a number of effects on the immune system, influencing MS. Recent research revealed a bidirectional relationship between metabolites originating from the gut microbiota, namely short-chain fatty acids (SCFAs). Intestinal epithelial cells are influenced by SCFAs, which also boosts the secretion of -Defensins and regenerating islet-derived III (REGIII) proteins. These proteins reduce intestinal pathogens, induce T-reg differentiation, and modulate immune responses by reducing IL-1 and IL-6 expression and increasing IL-10. Nutrition and psychological stress are two of the most significant elements that can directly and indirectly change the microbiota compositions along with other environmental influencing factors. An important regulator of intestinal physiology in the gut-brain-microbiota axis is butyrate, a well-known SCFA. Intestinal dysbiosis, altered intestinal barrier function, behavioral abnormalities, and activation of the hypothalamic-pituitary-adrenal (HPA) axis are all brought on by exposure. Probiotics, bacterial metabolite supplementation, fecal matter transplantation, defined microbial communities, and dietary intervention are some methods for modifying the composition of the gut microbiota that may be used to affect disease-related immune dysfunction and serve as the foundation for a new class of therapeutics.

Comprehensive Investigations Relationship Between Viral Infections and Multiple Sclerosis Pathogenesis.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Compared to other types of self-limiting myelin disorders, MS compartmentalizes and maintains chronic inflammation in the CNS. Even though the exact cause of MS is unclear, it is assumed that genetic and environmental factors play an important role in susceptibility to this disease. The progression of MS is triggered by certain environmental factors, such as viral infections. The most important viruses that affect MS are Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human endogenous retrovirus (HERV), cytomegalovirus (CMV), and varicella zoster virus (VZV). These viruses all have latent stages that allow them to escape immune detection and reactivate after exposure to various stimuli. Furthermore, their tropism for CNS and immune system cells explains their possible deleterious function in neuroinflammation. In this study, the effect of viral infections on MS disease focuses on the details of viruses that can change the risk of the disease. Paying attention to the most recent articles on the role of SARS-CoV-2 in MS disease, laboratory indicators show the interaction of the immune system with the virus. Also, strategies to prevent viruses that play a role in triggering MS are discussed, such as EBV, which is one of the most important.

Emerging importance of nanotechnology-based approaches to control the COVID-19 pandemic; focus on nanomedicine iterance in diagnosis and treatment of COVID-19 patients.

The ongoing outbreak of the newly emerged coronavirus disease 2019, which has tremendously concerned global health safety, is the result of infection with severe acute respiratory syndrome of coronavirus 2 with high morbidity and mortality. Because of the coronavirus has no specific treatment, so it is necessary to early detection and produce antiviral agents and efficacious vaccines in order to prevent the contagion of coronavirus. Due to the unique properties of nanomaterials, nanotechnology appears to be a highly relevant discipline in this global emergency, providing expansive chemical functionalization to develop advanced biomedical tools. Fascinatingly, nanomedicine as a hopeful approach for the treatment and diagnosis of diseases, could efficiently help success the fight among coronavirus and host cells. In this review, we will critically discuss how nanomedicine can play an indispensable role in creating useful treatments and diagnostics for coronavirus.

Synergistic Antiproliferative Effects of Co-nanoencapsulated Curcumin and Chrysin on MDA-MB-231 Breast Cancer Cells Through Upregulating miR-132 and miR-502c.

In this study, we explored whether co-nanoencapsulated Curcumin (Cur) and Chrysin (Chr), natural herbal compounds with antitumor activities, regulate miR-132 and miR-502c and their downstream targets, leading to the synergistic growth inhibition in MDA-MB-231 breast cancer cells. For this purpose, Cur and Chr were co-encapsulated into PLGA-PEG nanoparticles (NPs) and characterized through DLS, FTIR and FE-SEM. MTT assay and cell cycle arrest analysis revealed that CurChr-loaded NPs had a considerable synergistic cytotoxicity against MDA-MB-231 cells with more cell accumulation in G2/M phase compared to the other groups. In addition, highest percentage of cell apoptosis was acquired in cells treated with CurChr-loaded NPs according to apoptosis analysis. Real-time PCR findings revealed that co-encapsulated form of Cur and Chr than free combination could further upregulate miR-132 and miR-502c expression (P < 0.001). Also, the strong reduction was detected in the protein levels of HN1 and P65 at the cells co-nanodelivered with Cur and Chr. These findings demonstrated that the co-nanodelivery of Cur and Chr through targeting miR-132 and miR-205c might be a novel strategy for the treatment of breast cancer.

Co-Delivery of Curcumin and Chrysin by Polymeric Nanoparticles Inhibit Synergistically Growth and hTERT Gene Expression in Human Colorectal Cancer Cells.

Nanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in colorectal cancer therapy. Here, two well-known herbal substances, Curcumin (Cur) and Chrysin (Chr), were co-encapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against Caco-2 cancer cells. Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nano-encapsulated drugs on expression level of hTERT in Caco-2 cells. The results showed that free drugs and nano-formulations exhibited a dose-dependent cytotoxicity against Caco-2 cells and especially, Cur-Chr-PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (P < 0.05). Real-time PCR results revealed that Cur, Chr, and combination of Cur-Chr in free and encapsulated forms inhibited hTERT gene expression. Also, it was found that Cur-Chr-PLGA/PEG NPs than free combination forms could further decline hTERT expression in all concentration (P < 0.05). In summary, our study represents the first report of nano-combinational application of the natural herbal substances with a one-step fabricated codelivery system for effective colorectal cancer combinational chemotherapy.