Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

miRNAs as short non-coding RNAs in regulating doxorubicin resistance.

The treatment of cancer patients has been prohibited by chemoresistance. Doxorubicin (DOX) is an anti-tumor compound disrupting proliferation and triggering cell cycle arrest via inhibiting activity of topoisomerase I and II. miRNAs are endogenous RNAs localized in cytoplasm to reduce gene level. Abnormal expression of miRNAs changes DOX cytotoxicity. Overexpression of tumor-promoting miRNAs induces DOX resistance, while tumor-suppressor miRNAs inhibit DOX resistance. The miRNA-mediated regulation of cell death and hallmarks of cancer can affect response to DOX chemotherapy in tumor cells. The transporters such as P-glycoprotein are regulated by miRNAs in DOX chemotherapy. Upstream mediators including lncRNAs and circRNAs target miRNAs in affecting capacity of DOX. The response to DOX chemotherapy can be facilitated after administration of agents that are mostly phytochemicals including curcumol, honokiol and ursolic acid. These agents can regulate miRNA expression increasing DOX's cytotoxicity. Since delivery of DOX alone or in combination with other drugs and genes can cause synergistic impact, the nanoparticles have been introduced for drug sensitivity. The non-coding RNAs determine the response of tumor cells to doxorubicin chemotherapy. microRNAs play a key role in this case and they can be sponged by lncRNAs and circRNAs, showing interaction among non-coding RNAs in the regulation of doxorubicin sensitivity.

The growth inhibitory and apoptotic effects of umbelliprenin in a mouse model of systemic candidiasis.

AIMS: Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis. METHODS AND RESULTS: First, an antimicrobial assay via microdilution sensitivity test was performed. Then, twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The ß-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of ß-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1). CONCLUSION: Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis.

Curcumin neuroprotective effects in Parkinson disease during pregnancy.

BACKGROUND: Young onset Parkinson disease (YOPD) accounts for about 10% of PD patients, with the onset of symptoms between the ages of 21 and 40. At this age, the probability of pregnancy is high and there is a concern that the disease affects the fetuses. Therefore, in the present study, the effects of rotenone-induced PD on female mice as well as their fetuses and curcumin supplementation on the cerebral tissue of both female mice and their resulted fetuses were studied. METHODS: The rotenone was injected subcutaneously to induce PD model of female mice. The different concentrations of curcumin were administrated every day i.p. for 3 weeks and the rotarod test was done on day 1 and 19. Cell viability was measured by MTT test and apoptosis and necrosis of cells were evaluate using flow cytometry technique. After primer design, the expressions of bax, bcl-2, miR-211 and circRNA 0001518 genes were measured using RT-PCR technique. RESULTS: Curcumin administration were improved cerebral cell viability of both female PD mice and resulted fetuses by preventing cell apoptosis and necrosis. bax, miR-211 and circRNA 0001518 were downregulated and bcl-2 overexpressed in cerebral neurons of PD mice and their fetuses. CONCLUSION: PD induction in mice affects their fetal brain, and curcumin can partially reduce the negative effects of PD on fetal brain cells by overexpressing bcl-2 and decreasing bax expression genes.

Molecular profile of non-coding RNA-mediated glycolysis control in human cancers.

The glycolysis is a common characteristic of cancer and it is responsible for providing enough energy to ensure growth. The glycolysis suppression is beneficial in tumor growth reduction. The stimulation/inhibition of glycolysis in cancer is tightly regulated by ncRNAs. The regulation of glycolysis by ncRNAs can influence proliferation and therapy response of tumor. The miRNAs are capable of inactivating enzymes responsible for glycolysis and suppressing signaling networks resulting in glycolysis induction. By regulation of glycolysis, miRNAs can affect therapy response. The lncRNAs and circRNAs follow a same pathway and by targeting glycolysis, they affect progression and therapy response of tumor. Noteworthy, lncRNAs and circRNAs sponge miRNAs in glycolysis mechanism control in tumor cells. Furthermore, ncRNA-mediated regulation of glycolysis mechanism can influence metastasis to organs of body. The ncRNAs regulating glycolysis are reliable biomarkers in cancer patients and more importantly, exosomal ncRNAs due to their presence in body fluids, are minimally-invasive biomarkers.

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer.

Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki-67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E-cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti-cancer agent for BC that can synergize with other chemotherapeutics.

Hypoxia inducible factor-1α (HIF-1α) in breast cancer: The crosstalk with oncogenic and onco-suppressor factors in regulation of cancer hallmarks.

Low oxygen level at tumor microenvironment leads to a condition, known as hypoxia that is implicated in cancer progression. Upon hypoxia, HIF-1α undergoes activation and due to its oncogenic function and interaction with other molecular pathways, promotes tumor progression. The HIF-1α role in regulating breast cancer progression is described, Overall, HIF-1α has upregulation in breast tumor and due to its tumor-promoting function, its upregulation is in favor of breast tumor progression. HIF-1α overexpression prevents apoptosis in breast tumor and it promotes cell cycle progression. Silencing HIF-1α triggers cycle arrest and decreases growth. Migration of breast tumor enhances by HIF-1α signaling and it mainly induces EMT in providing metastasis. HIF-1α upregulation stimulates drug resistance and radio-resistance in breast tumor. Furthermore, HIF-1α signaling induces immune evasion of breast cancer. Berberine and pharmacological intervention suppress HIF-1α signaling in breast tumor and regulation of HIF-1α by non-coding RNAs occurs. Furthermore, HIF-1α is a biomarker in clinic.

Evaluation of the expression level of some coding and non-coding genes in oral squamous cell carcinoma.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the most common cancers arising from the head and neck region. There is growing evidence that lncRNAs play an important role in OSCC progression. The study aims to investigate correlations between the expression levels of LncRNAs of PARROT, MYCNUT, DANCR, and KTN1-AS1 with clinicopathological characteristics and finding suitable biomarkers for OSCC. MATERIAL AND METHOD: Total lncRNAs related to cancers and HNSC trascriptomics data were downloaded from lncRNADisease v2.0 database and xenabrowser, respectively. Then, ACO was perfomed on shared of LncRNAs between two databases. Finally, some lncRNAs were proposed as potential biomarkers. Thirty biopsies samples from patients with the OSCC and 30 healthy subjects were collected by the surgery. Questionnaires including clinical and demographic data were filled for all cases. Using Real-time PCR, the expression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 lncRNAs were quantified. RESULT: According to the results,17 novel gene symbol was identified.All the candidate lncRNAs the expression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 were remarkably upregulated in OSCC tumors in comparison with control group (RQ: 10.00 (P < 0.0001), RQ: 2.920 (P < 0.0001), RQ: 1.623 (P = 0.002), and 4.467 (P < 0.0001), respectively). Also, we found significant associations between tumor lncRNAs expression of PARRPT and DANCER and tumor metastasis (P = 0.009, and P = 0.005, respectively). Additionally, lncRNA KTN1-AS1 expression level was significantly higher in the patients with tumor size more than 3 cm, in comparison with tumor less than 3 cm (P = 0.005). According ROC analysis, all these candidate lncRNAs can be a significant predictor for OSCC (AUC of PARROT lncRNA = 69.72%, AUC of MYCNUT = 98.22%, AUC of DANCR = 74.83%, and AUC of KTN1-AS1 = 99.22%). CONCLUSION: we found that overexpression levels of PARROT, MYCNUT, DANCR, and KTN1-AS1 lncRNAs were correlated with poor clinicopathological characteristics in patients with OSCC. Also, PARROT, MYCNUT, DANCR, and KTN1-AS1 are novel biomarker for the detection of OSCC.

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy.

Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.

Exosome-mediated miR-200a delivery into TGF-ß-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression.

Exosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential regulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-ß for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading efficiency of 5.92 ± 4.6%. The TGF-ß treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of ß-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells.

siRNA and targeted delivery systems in breast cancer therapy

Recently, nucleic acid drugs have been considered as promising candidates in treatment of various diseases, especially cancer. Because of developing resistance to conventional chemotherapy, use of genetic tools in cancer therapy appears inevitable. siRNA is a RNAi tool with capacity of suppressing target gene. Owing to overexpression of oncogenic factors in cancer, siRNA can be used for suppressing those pathways. This review emphasizes the function of siRNA in treatment of breast tumor. The anti-apoptotic-related genes including Bcl-2, Bcl-xL and survivin can be down-regulated by siRNA in triggering cell death in breast cancer. STAT3, STAT8, Notch1, E2F3 and NF-κB are among the factors with overexpression in breast cancer that their silencing by siRNA paves the way for impairing tumor proliferation and invasion. The oncogenic mechanisms in drug resistance development in breast tumor such as lncRNAs can be suppressed by siRNA. Furthermore, siRNA reducing P-gp activity can increase drug internalization in tumor cells. Because of siRNA degradation at bloodstream and low accumulation at tumor site, nanoplatforms have been employed for siRNA delivery to suppress breast tumor progression via improving siRNA efficacy in gene silencing. Development of biocompatible and efficient nanostructures for siRNA delivery can make milestone progress in alleviation of breast cancer patients (AU)

Wnt/ß-catenin Signaling in Lung Cancer: Association with Proliferation, Metastasis, and Therapy Resistance.

The capacity of cancer cells for abnormal growth and metastasis has made it difficult to find a cure for tumor. Both males and females suffer from lung tumors, and physicians still deem them incurable. The initiation and development of lung tumors can be forced by genomic mutations. Wnt is a critical pathway for regulating growth, differentiation and migration. However, its oncogenic function has been observed in lung cancer. Wnt is able to increase the proliferation of lung tumors. The metastasis potential of lung tumors can be accelerated by Wnt/EMT axis. Overexpression of Wnt/ß-catenin prevents chemotherapy-mediated cell death in lung tumors. This pathway promotes cancer stem cell features in lung tumors which induce radioresistance. Anti-cancer agents, such as curcumin, are able to inhibit Wnt in lung tumor treatment. Wnt interaction with other factors in lung tumors is essential in controlling biological behavior, and non-coding RNA transcripts are the most well-known ones. It can be concluded from the current study that Wnt is an important regulator of lung tumorigenesis, and the translation of these findings into the clinic is vital.

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

Diagnostic and therapeutic potential of LINC01929 as an oncogenic LncRNA in human cancers.

Recent findings have shown the significant role of long non-coding RNAs in the pathogenesis of various cancers. In this regard, the variation in the expression of LINC01929 was explored in various cancers to explore its impact on the development of diverse malignancies and cancers. The data of the cancer genome atlas (TCGA) were utilized to evaluate the changes in the expression of LINC01929 in various cancers, as well as its relationship with the patients' survival rate. The co-expression of the genes and data merging of TCGA were utilized to identify the LINC01929-associated pathways. The samples of colorectal, gastric, and breast cancers were also examined by the RT-qPCR to confirm the results and evaluate the expression of LINC01929 in the mentioned cancers. In silico investigations indicated a remarkable enhancement in the expression of LINC01929 within the tumor tissues compared to normal samples in 10 types of cancer. Based on the survival results, the increase in the LINC01929 expression is linked to poor prognosis of bladder, breast, colorectal, kidney, and liver cancers. The gene co-expression network showed the strong co-expression of LINC01929 with genes involved in the metastatic pathways including COL5A1. RT-qPCR findings showed a remarkable increment in the expression level of LINC01929 in the colorectal, gastric, and breast tumor tissues versus the adjacent normal tissues. A significant and strong relationship was also found between the expression of LINC01929 and COL5A1. This study indicated a significant enhancement in the expression level of LINC01929 in various cancer types, accompanied by the mortality rate. Moreover, LINC01929 exhibited a strong co-expression with the metastatic genes such as COL5A1. As an oncogene and regulator of the metastatic pathways, LINC01929 can be a proper candidate for diagnostic and therapeutic purposes.

STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions.

The categorization of cancers demonstrates that prostate cancer is the most common malignancy in men and it causes high death annually. Prostate cancer patients are diagnosed mainly via biomarkers such as PSA test and patients show poor prognosis. Prostate cancer cells rapidly diffuse into different parts of body and their metastasis is also a reason for death. Current therapies for prostate cancer patients include chemotherapy, surgery and radiotherapy as well as targeted therapy. The progression of prostate cancer cells is regulated by different factors that STAT3 signaling is among them. Growth factors and cytokines such as IL-6 can induce STAT3 signaling and it shows carcinogenic impact. Activation of STAT3 signaling occurs in prostate cancer and it promotes malignant behavior of tumor cells. Induction of STAT3 signaling increases glycolysis and proliferation of prostate cancer cells and prevents apoptosis. Furthermore, STAT3 signaling induces EMT mechanism in increasing cancer metastasis. Activation of STAT3 signaling stimulates drug resistance and the limitation of current works is lack of experiment related to role of STAT3 signaling in radio-resistance in prostate tumor. Calcitriol, capsazepine and ß-elemonic are among the compounds capable of targeting STAT3 signaling and its inhibition in prostate cancer therapy. In addition to natural products, small molecules targeting STAT3 signaling have been developed in prostate cancer therapy.

Unraveling the function of epithelial-mesenchymal transition (EMT) in colorectal cancer: Metastasis, therapy response, and revisiting molecular pathways.

Colorectal cancer (CRC) is a dangerous form of cancer that affects the gastrointestinal tract. It is a major global health concern, and the aggressive behavior of tumor cells makes it difficult to treat, leading to poor survival rates for patients. One major challenge in treating CRC is the metastasis, or spread, of the cancer, which is a major cause of death. In order to improve the prognosis for patients with CRC, it is necessary to focus on ways to inhibit the cancer's ability to invade and spread. Epithelial-mesenchymal transition (EMT) is a process that is linked to the spread of cancer cells, also known as metastasis. The process transforms epithelial cells into mesenchymal ones, increasing their mobility and ability to invade other tissues. This has been shown to be a key mechanism in the progression of colorectal cancer (CRC), a particularly aggressive form of gastrointestinal cancer. The activation of EMT leads to increases in the spread of CRC cells, and during this process, levels of the protein E-cadherin decrease while levels of N-cadherin and vimentin increase. EMT also contributes to the development of resistance to chemotherapy and radiation therapy in CRC. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a role in regulating EMT in CRC, often through their ability to "sponge" microRNAs. Anti-cancer agents have been shown to suppress EMT and reduce the progression and spread of CRC cells. These findings suggest that targeting EMT or related mechanisms may be a promising approach for treating CRC patients in the clinic.

The pharmacological and biological importance of EZH2 signaling in lung cancer.

Up to 18% of cancer-related deaths worldwide are attributed to lung tumor and global burden of this type of cancer is ascending. Different factors are responsible for development of lung cancer such as smoking, environmental factors and genetic mutations. EZH2 is a vital protein with catalytic activity and belongs to PCR2 family. EZH2 has been implicated in regulating gene expression by binding to promoter of targets. The importance of EZH2 in lung cancer is discussed in current manuscript. Activation of EZH2 significantly elevates the proliferation rate of lung cancer. Furthermore, metastasis and associated molecular mechanisms including EMT undergo activation by EZH2 in enhancing the lung cancer progression. The response of lung cancer to therapy can be significantly diminished due to EZH2 upregulation. Since EZH2 increases tumor progression, anti-cancer agents suppressing its expression reduce malignancy. In spite of significant effort in understanding modulatory function of EZH2 on other pathways, it appears that EZH2 can be also regulated and controlled by other factors that are described in current review. Therefore, translating current findings to clinic can improve treatment and management of lung cancer patients.

(Nano)platforms in bladder cancer therapy: Challenges and opportunities.

Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo-loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH-, redox-, and light-responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review.

Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy.

Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.

Graphene oxide nanoarchitectures in cancer biology: Nano-modulators of autophagy and apoptosis.

Nanotechnology is a growing field, with many potential biomedical applications of nanomedicine for the treatment of different diseases, particularly cancer, on the horizon. Graphene oxide (GO) nanoparticles can act as carbon-based nanocarriers with advantages such as a large surface area, good mechanical strength, and the capacity for surface modification. These nanostructures have been extensively used in cancer therapy for drug and gene delivery, photothermal therapy, overcoming chemotherapy resistance, and for imaging procedures. In the current review, we focus on the biological functions of GO nanoparticles as regulators of apoptosis and autophagy, the two major forms of programmed cell death. GO nanoparticles can either induce or inhibit autophagy in cancer cells, depending on the conditions. By stimulating autophagy, GO nanocarriers can promote the sensitivity of cancer cells to chemotherapy. However, by impairing autophagy flux, GO nanoparticles can reduce cell survival and enhance inflammation. Similarly, GO nanomaterials can increase ROS production and induce DNA damage, thereby sensitizing cancer cells to apoptosis. In vitro and in vivo experiments have investigated whether GO nanomaterials show any toxicity in major body organs, such as the brain, liver, spleen, and heart. Molecular pathways, such as ATG, MAPK, JNK, and Akt, can be regulated by GO nanomaterials, leading to effects on autophagy and apoptosis. These topics are discussed in this review to shed some lights towards the biomedical potential of GO nanoparticles and their biocompatibility, paving the way for their future application in clinical trials.