An exosomal approach for oral delivery of resveratrol: Implications for inflammatory bowel disease treatment in rat model.

AIMS: Resveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches. MAIN METHODS: The current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models. KEY FINDINGS: The results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis. SIGNIFICANCE: Our findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations.

Enhanced Myocardial Tissue Visualization: A Comparative Cardiovascular Magnetic Resonance Study of Gradient-Spin Echo-STIR and Conventional STIR Imaging.

Purpose: This study is aimed at evaluating the efficacy of the gradient-spin echo- (GraSE-) based short tau inversion recovery (STIR) sequence (GraSE-STIR) in cardiovascular magnetic resonance (CMR) imaging compared to the conventional turbo spin echo- (TSE-) based STIR sequence, specifically focusing on image quality, specific absorption rate (SAR), and image acquisition time. Methods: In a prospective study, we examined forty-four normal volunteers and seventeen patients referred for CMR imaging using conventional STIR and GraSE-STIR techniques. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, T2 signal intensity (SI) ratio, SAR, and image acquisition time were compared between both sequences. Results: GraSE-STIR showed significant improvements in image quality (4.15 ± 0.8 vs. 3.34 ± 0.9, p = 0.024) and cardiac motion artifact reduction (7 vs. 18 out of 53, p = 0.038) compared to conventional STIR. Furthermore, the acquisition time (27.17 ± 3.53 vs. 36.9 ± 4.08 seconds, p = 0.041) and the local torso SAR (<13% vs. <17%, p = 0.047) were significantly lower for GraSE-STIR compared to conventional STIR in short-axis plan. However, no significant differences were shown in T2 SI ratio (p = 0.141), SNR (p = 0.093), CNR (p = 0.068), and SAR (p = 0.071) between these two sequences. Conclusions: GraSE-STIR offers notable advantages over conventional STIR sequence, with improved image quality, reduced motion artifacts, and shorter acquisition times. These findings highlight the potential of GraSE-STIR as a valuable technique for routine clinical CMR imaging.

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off-the-shelf versatile tumor delivery vehicle.

Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

Signaling crosstalk between mesenchymal stem cells and tumor cells: Implications for tumor suppression or progression.

Mesenchymal stem cells (MSCs) have been extensively used in various therapeutic applications over the last two decades, particularly in regenerative medicine and cancer treatment. MSCs have the ability to differentiate into mesodermal and non-mesodermal lineages, which makes them a popular choice in tissue engineering and regenerative medicine. Studies have shown that MSCs have inherent tumor-suppressive properties and can affect the behavior of multiple cells contributing to tumor development. Additionally, MSCs possess a tumor tropism property and have a hypoimmune nature. The intrinsic features of MSCs along with their potential to undergo genetic manipulation and be loaded with various anticancer therapeutics have motivated researchers to use them in different cancer therapy approaches without considering their complex dynamic biological aspects. However, despite their desirable features, several reports have shown that MSCs possess tumor-supportive properties. These contradictory results signify the sophisticated nature of MSCs and warn against the potential therapeutic applications of MSCs. Therefore, researchers should meticulously consider the biological properties of MSCs in preclinical and clinical studies to avoid any undesirable outcomes. This manuscript reviews preclinical studies on MSCs and cancer from the last two decades, discusses how MSC properties affect tumor progression and explains the mechanisms behind tumor suppressive and supportive functions. It also highlights critical cellular pathways that could be targeted in future studies to improve the safety and effectiveness of MSC-based therapies for cancer treatment. The insights obtained from this study will pave the way for further clinical research on MSCs and development of more effective cancer treatments.

The Role of Improved Motion-Sensitized Driven Equilibrium Blood Suppression and Fat Saturation on T2 Relaxation Time, Using GraSE Sequence in Cardiac Magnetic Resonance Imaging.

BACKGROUND: T2 mapping is a valuable technique in cardiac MR imaging that offers insights into the microstructural characteristics of myocardial tissue. However, it was shown that myocardial T2 relaxation times (T2 ) measured vary significantly depending on sequence, sequence parameters, and field strength. PURPOSE: To assess T2 variability and image quality in cardiac T2 maps using four variants of the gradient-spin echo (GraSE) sequence, having different methods of blood signal suppression (double inversion recovery (DIR) and improved motion-sensitized driven equilibrium (iMSDE) and with and without the addition of fat saturation (FS). STUDY TYPE: Prospective. POPULATION: 48 healthy volunteers (46.7 +/- 21.5 years, 24 male) with no cardiac history. FIELD STRENGTH/SEQUENCE: GraSE sequence with DIR (GraSEDIR ), with iMSDE (GraSEiMSDE ) and FS (GraSEDIR -FS) and with both iMSDE and FS (GraSEiMSDE -FS) at 1.5T. ASSESSMENT: Global T2 from three short axis myocardial slices. and image quality assessments using a 5-point Lickert scale (1, (non-diagnostic) to 5, (excellent)) were conducted to evaluate the impact of DB and FS techniques on myocardial T2 measurements and image quality. STATISTICAL TESTS: Paired t-tests or non-parametric equivalents for comparisons between sequences. The Bland-Altmann plots and Pearson rank correlation analyses, as appropriate. A P value <0.05 was considered statistically significant. RESULTS: The mean global T2 values for GraSEDIR , GraSEDIR -FS, GraSEiMSDE , and GraSEiMSDE -FS, were 52.84 ± 5.72 msec, 54.98 ± 3.59 msec, 53.9 ± 4.05 msec, and 55.14 ± 4.28 msec, respectively, with no significant differences (P = 0.092). High image quality scores (>4 out of 5) were obtained for all sequence variants with no significant differences between them (P = 0.11). DATA CONCLUSION: All GraSE sequence variants exhibited approximately the same results and variations in the DB technique and addition of FS did not have significant impact on myocardial T2 values. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

PNA-ATP aptamer-capped doxorubicin-loaded silica nanoparticles for targeted cancer therapy.

Nanomaterial-based drug delivery has opened new horizons in cancer therapy. This study aimed to investigate the in vitro and in vivo anti-cancer effects of a hyaluronic acid (HA)-targeted nanocarrier based on hollow silica nanoparticles (HSNPs), gated with peptide nucleic acid (PNA) and ATP aptamer (ATPApt) and loaded with doxorubicin (DOX). After formulation of a smart drug delivery nanosystem (HSNPs/DOX/ATPApt/PNA/HA), drug release, cytotoxicity, uptake, and in vivo anti-tumor properties were studied. Drug release test showed the controlled release of encapsulated DOX in response to ATP content. MTT and flow cytometry indicated that HA could improve both cytotoxicity and cellular uptake of the formulation. Moreover, HA-targeted formulation enhanced both the survival rate and tumor inhibition in the tumor-bearing mice compared with free DOX (P < 0.05). Our findings confirmed that HA-targeted nanoformulation, gated with PNA/aptamer and loaded with DOX can provide a novel therapeutic platform with great potential for cancer therapy.

Recent progress in the early detection of cancer based on CD44 biomarker; nano-biosensing approaches.

CD44 is a cell matrix adhesion molecule overexpressed on the cell surfaces of the major cancers. CD44 as a cancer-related biomarker has an essential role in the invasion and metastasis of cancer. The detection and quantification of CD44 can provide essential information useful for clinical cancer diagnosis. In this regard, biosensors with sensitive and specific properties, give prominence to the development of CD44 detection platforms. To date, various aptamer-based sensitive-enhancers together with nanoparticles (NPs) have been combined into the biosensors systems to provide an innovative biosensing method (aptasensors/nano-aptasensors) with substantially improved detection limit. This review article discusses the recent advances in the field of biosensors, nanobiosensors, and aptasensors for the quantitative determination of CD44 and the detection of CD44-expressing cancer cells.

Platinum Nanoparticles in Biomedicine: Preparation, Anti-Cancer Activity, and Drug Delivery Vehicles.

Cancer is the main cause of morbidity and mortality worldwide, excluding infectious disease. Because of their lack of specificity in chemotherapy agents are used for cancer treatment, these agents have severe systemic side effects, and gradually lose their therapeutic effects because most cancers become multidrug resistant. Platinum nanoparticles (PtNPs) are relatively new agents that are being tested in cancer therapy. This review covers the various methods for the preparation and physicochemical characterization of PtNPs. PtNPs have been shown to possess some intrinsic anticancer activity, probably due to their antioxidant action, which slows tumor growth. Targeting ligands can be attached to functionalized metal PtNPs to improve their tumor targeting ability. PtNPs-based therapeutic systems can enable the controlled release of drugs, to improve the efficiency and reduce the side effects of cancer therapy. Pt-based materials play a key role in clinical research. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, stability, solubility, the method of production, biodistribution, accumulation, controlled release, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics.

Self-assembly of an aptamer-decorated chimeric peptide nanocarrier for targeted cancer gene delivery.

In this study, we developed a peptide-based non-viral carrier decorated with aptamer to overcome the specific gene delivery barriers. The carrier (KLN/Apt) was designed to contain multiple functional segments, including 1) two tandem repeating units of low molecular weight protamine (LMWP) to condense DNA into stable nanosize particles and protect it from enzymatic digestion, 2) AS1411 aptamer as targeting moiety to target nucleolin and promote carrier internalization, 3) a synthetic pH-sensitive fusogenic peptide (KALA) for disrupting endosomal membranes and enhancing cytosol escape of the nanoparticles, and 4) a nuclear localization signal (NLS) for active cytoplasmic trafficking and nuclear delivery of DNA. The obtained results revealed the developed carrier capacity in terms of specific cell targeting, overcoming cellular gene delivery barriers, and mediating efficient gene transfection. The KLN/pDNA/aptamer nanoparticles offer remarkable potential for the conceptual design and formation of promising multi-functionalized carriers towards the most demanding therapeutic applications.

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma.

Recently, the siderophores have opened new horizons in nanomedicine. The current study aimed to design a theranostic platform based on superparamagnetic iron oxide nanoparticles-pyoverdine (SPION/PVD) conjugates bound to MUC1 aptamer (MUC1Apt) and loaded with doxorubicin (DOX) as an anti-cancer agent. The SPION/PVD complex was covalently conjugated to MUC1Apt and loaded with DOX to prepare a targeted drug delivery system (SPION/PVD/MUC1Apt/DOX). The investigation of cellular cytotoxicity and uptake of formulations by MTT and flow cytometry in both MUC1 positive (C26) and MUC1 negative (CHO) cell lines revealed that MUC1Apt could improve both cellular uptake and toxicity in the C26 cell line. The evaluation of tumor-targeting activity by in vivo bio-distribution showed that the targeted formulation could enhance tumor inhibitory growth effect and survival rate in C26 tumor-bearing mice. Furthermore, the potential of synthesized SPION/PVD/MUC1Apt/DOX complex as diagnostic agents was investigated by magnetic resonance imaging (MRI) which improved the contrast of tumor site in MRI. Our findings confirm that aptamer-targeted PVD chelated the SPION as a diagnostic agent and loaded with DOX as a chemotherapeutic drug, would be beneficial as a novel theranostic platform.

Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials.

PURPOSE: Oxidative stress (OS) is associated with several chronic complications and diseases. The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown to be beneficial. However, the impact of CoQ10 as a preventive agent against OS has not been systematically investigated. METHODS: A systematic literature search was performed using the PubMed, SCOPUS, EMBASE, and Cochrane Library databases to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. RESULTS: Seventeen randomized clinical trials met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD - 0.94; 95% CI - 1.46, - 0.41; I2 = 87.7%) and a significant increase in total antioxidant capacity (TAC) (SMD 0.67; 95% CI 0.28, 1.07; I2 = 74.9%) and superoxide dismutase (SOD) activity (SMD 0.40; 95% CI 1.12, 0.67; I2 = 9.6%). The meta-analysis found no statistically significant impact of CoQ10 supplementation on nitric oxide (NO) (SMD - 1.40; 95% CI - 0.12, 1.93; I2 = 92.6%), glutathione (GSH) levels (SMD 0.41; 95% CI - 0.09, 0.91; I2 = 70.0%), catalase (CAT) activity (SMD 0.36; 95% CI - 0.46, 1.18; I2 = 90.0%), or glutathione peroxidase (GPx) activities (SMD - 1.40; 95% CI: - 0.12, 1.93; I2 = 92.6%). CONCLUSION: CoQ10 supplementation, in the tested range of doses, was shown to reduce MDA concentrations, and increase TAC and antioxidant defense system enzymes. However, there were no significant effects of CoQ10 on NO, GSH concentrations, or CAT activity.

Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis. CONCLUSIONS: Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.

Topical application of curcumin regulates the angiogenesis in diabetic-impaired cutaneous wound.

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin-induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re-epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor-κB (NF-κB) signalling pathway. However, no significant effects on macrophage polarization and re-epithelialization were observed in the curcumin-treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis-promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation. SIGNIFICANCE OF THE STUDY: Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti-inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high-dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re-emphasize the proangiogenic potential of curcumin in diabetic wound environment.

Multifunctional MIL-Cur@FC as a theranostic agent for magnetic resonance imaging and targeting drug delivery: in vitro and in vivo study.

Owing to the importance of multifunctional theranostics as promising systems to overcome key problems of conventional cancer therapy, in this study a multifunctional metal-organic framework-based (MOF) theranostic system was prepared and applied as intelligent theranostic systems in cancer. Iron-based MOF, MIL-88B, in a multi-faceted shape was initially prepared. Curcumin (Cur) was then loaded into the pores of MIL and folic acid-chitosan conjugate (FC) was finally coated on the surface of the carrier to accomplish cancer-specific targeting properties. MTT assay revealed perfect cytocompatibility of the system and selective toxicity against cancerous cells. In vivo MRI images showed high tumour uptake for MIL-Cur@FC and high T1-T2 contrast effect. The growth inhibiting efficiencies of MIL-Cur@FC on M109 tumour bearing Balb/C mice without reducing their body weight showed maximum tumour eradication with no significant toxicities. Due to the outstanding features of the system achieved from in vitro and in vivo studies, we believe that this study will provide a novel approach for developing targeted theranostic agents in cancer diagnosis and treatment.

Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer.

BACKGROUND: Lung cancer is the second most common cancer and the main cause of cancer-related mortality worldwide. In spite of various efforts that have been made to facilitate the early diagnosis of lung cancer, most patients are diagnosed when the disease is already in stage IV, which is generally associated with the occurrence of distant metastases and a poor survival. Moreover, a large proportion of these patients will relapse after treatment, heralding the need for the stratification of lung cancer patients in addition to identifying those who are at a higher risk of relapse and, thus, require alternative and/or additional therapies. Recently, circulating tumor cells (CTCs) have been considered as valuable markers for the early diagnosis, prognosis and risk stratification of cancer patients, and they have been found to be able to predict the survival of patients with various types of cancer, including lung cancer. Additionally, the characterization of CTCs has recently provided fascinating insights into the heterogeneity of tumors, which may be instrumental for the development of novel targeted therapies. CONCLUSIONS: Here we review our current understanding of the significance of CTCs in lung cancer metastasis. We also discuss prominent studies reporting the utility of enumeration and characterization of CTCs in lung cancer patients as prognostic and pharmacodynamic biomarkers for those who are at a higher risk of metastasis and drug resistance.

Optical and electrochemical-based nano-aptasensing approaches for the detection of circulating tumor cells (CTCs).

More recently, detection of circulating tumor cells (CTCs) has been considered as an appealing prognostic and diagnostic approach for cancer patients. CTCs as a type of tumor-derived cells are secreted by the tumor and released into the blood circulation. Since the migration of CTCs is an early event in cancer progression, patients who still have tumor-free lymph nodes have to be well examined for the CTCs presence in their blood circulation. Nowadays, there is a broad range of detection methods available to identify CTCs. As artificial RNA oligonucleotides or single-stranded DNA with receptor and catalytic characteristics, aptamers have been standing out, owing to their target-induced conformational modifications, elevated stability, and target specificity to be implemented in biosensing techniques. To date, several sensitivity-enhancement methods alongside smart nanomaterials have been used for the creation of new aptasensors to address the limit of detection (LOD), and improve the sensitivity of numerous analyte identification methods. The present review article supports a focused overview of the recent studies in the identification and quantitative determination of CTCs by aptamer-based biosensors and nanobiosensors.

Magnetic bio-metal-organic framework nanocomposites decorated with folic acid conjugated chitosan as a promising biocompatible targeted theranostic system for cancer treatment.

In this work, a multifunctional magnetic Bio-Metal-Organic Framework (Fe3O4@Bio-MOF) coated with folic acid-chitosan conjugate (FC) was successfully prepared for tumor-targeted delivery of curcumin (CUR) and 5-fluorouracil (5-FU) simultaneously. Bio-MOF nanocomposite based on CUR as organic linker and zinc as metal ion was prepared by hydrothermal method in the presence of amine-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@NH2 MNPs). 5-FU was loaded in the magnetic Bio-MOF and the obtained nanocarrier was then coated with FC network. The prepared nanocomposite (NC) was fully characterized by high resolution-transmission electron microscope (HR-TEM), field emission scanning electron microscopy (FE-SEM), Dynamic light scattering (DLS), X-ray diffraction analysis (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), nuclear magnetic resonance (NMR), and UV-vis analyses. In vitro release study showed controlled release of CUR and 5-FU in acidic pH confirming high selectivity and performance of the carrier in cancerous microenvironments. The selective uptake of 5-FU-loaded Fe3O4@Bio-MOF-FC by folate receptor-positive MDA-MB-231 cells was investigated and verified. The ultimate nanocarrier exhibited no significant toxicity, while drug loaded nanocarrier showed selective and higher toxicity against the cancerous cells than normal cells. SDS PAGE was also utilized to determine the protein pattern attached on the surface of the nanocarriers. In vitro and in vivo MRI studies showed negative signal enhancement in tumor confirming the ability of the nanocarrier to be applied as diagnostic agent. Owing to the selective anticancer release and cellular uptake, acceptable blood compatibility as well as suitable T2 MRI contrast performance, the target nanocarrier could be considered as favorable theranostic in breast cancer.

Gadolinium (III) oxide nanoparticles coated with folic acid-functionalized poly(ß-cyclodextrin-co-pentetic acid) as a biocompatible targeted nano-contrast agent for cancer diagnostic: in vitro and in vivo studies.

OBJECTIVES: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with ß-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). MATERIALS AND METHODS: The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. RESULTS: In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. CONCLUSION: The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.

Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review.

Mucin 1 protein (MUC1) is a membrane-associated glycoprotein overexpressed in the majority of human malignancies and considered as a predominant protein biomarker in cancers. Owing to the crucial role of MUC1 in cancer dissemination and metastasis, detection and quantification of this biomarker is of great importance in clinical diagnostics. Today, there exist a wide variety of strategies for the determination of various types of disease biomarkers, especially MUC1. In this regard, aptamers, as artificial single-stranded DNA or RNA oligonucleotides with catalytic and receptor properties, have drawn lots of attention for the development of biosensing platforms. So far, various sensitivity-enhancement techniques in combination with a broad range of smart nanomaterials have integrated into the design of novel aptamer-based biosensors (aptasensors) to improve detection limit and sensitivity of analyte determination. This review article provides a brief classification and description of the research progresses of aptamer-based biosensors and nanobiosensors for the detection and quantitative determination of MUC1 based on optical and electrochemical platforms.