Targeted delivery of elesclomol using a magnetic mesoporous platform improves prostate cancer treatment both in vitro and in vivo.

BACKGROUND: To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS). MATERIALS AND METHODS: ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo. RESULTS: The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug. CONCLUSION: Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.

Iranian National Survey on Tinea Capitis: Antifungal Susceptibility Profile, Epidemiological Characteristics, and Report of Two Strains with a Novel Mutation in SQLE Gene with Homology Modeling.

BACKGROUND: The data on the epidemiological and antifungal susceptibility profile of tinea capitis (TC) in Iran has not been updated in recent decades. This report presents the Iranian epidemiological and drug susceptibility data regarding the distribution of dermatophytes species isolated by six national mycology centers for a period of one year (2020-2021). MATERIAL AND METHODS: A total of 2100 clinical samples from individuals suspeted to TC were subjected to mycological analysis of direct microscopy and culture. For definite species identification, the culture isolates were additionally subjected to PCR-RFLP and PCR-sequencing of the ITS ribosomal DNA (ITS-rDNA) region. Antifungal susceptibility profiles for eight common antifungal drugs were determined by CLSI M38-A3 guidelines. The SQLE gene was partially amplified and sequenced in two terbinafine-resistant and two susceptible T. mentagrophytes isolates to elucidate probable substitutions involved in resistance. RESULTS: TC (n = 94) was diagnosed in 75 children (79.8%) and 19 adults (20.2%) by direct microscopy and culture. Frequency of TC was significantly more among males (66 males = 70.2% vs 28 females = 29.8%). The prevalent age group affected was 5-9 years (39.36%). Thirty-two (34.04%) T. mentagrophytes, 27 (28.7%) T. tonsurans, 14 (14.9%) M. canis, 13 (13.8%) T. violaceum, 5 (5.32%) T. indotineae, 2 (2.1%) T. benhamiae, and 1 (1.1%) T. schoenleinii were identified as the causative agents. MIC values of isolates showed susceptibility to all antifungal agents, except for fluconazole and griseofulvin with GM MIC of 11.91 µg/ml and 2.01 µg/ml, respectively. Terbinafine exhibited more activity against isolates, with GM MIC 0.084 µg/ml followed by ketoconazole (0.100 µg/ml), econazole (0.107 µg/ml), itraconazole (0.133 µg/ml), butenafine (0.142 µg/ml), and miconazole (0.325 µg/ml). Two resistant T. mentagrophytes isolates harbored missense mutations in SQLE gene, corresponding to amino acid substitution F397L. Remarkably, one unique mutation, C1255T, in the SQLE sequence of two terbinafine-susceptible T. mentagrophytes strains leading to a change of leucine at the 419th position to phenylalanine (L419F) was detected. CONCLUSIONS: T. mentagrophytes, T. tonsurans, and M. canis remained the main agents of TC in Iran, however less known species such as T. indotinea and T. benhamiae are emerging as new ones. Terbinafine could still be the appropriate choice for the treatment of diverse forms of TC.

First-principles study of lead-free Ge-based 2D Ruddlesden-Popper hybrid perovskites for solar cell applications.

Recently, 2D halide perovskites have attracted attention because they are excellent photo absorbing materials for perovskite solar cells. To date, the majority of 2D perovskite-based devices have been made of Pb, a material with toxic properties and environmental concerns. Thus, lead-free alternatives are essential to enable the expansion of photovoltaic systems based on perovskites. Herein, we examine the structural, electronic, optical and stability properties of Pb-free 2D Ruddlesden-Popper (RP) perovskites (BA)2(MA)n-1GenI3n+1 (BA = CH3(CH2)3NH3+; MA = CH3NH3+; n = 1-5, and ∝) by using DFT calculations and comparing the results to their Pb-based counterparts (BA)2(MA)n-1PbnI3n+1 (n = 1-5, and ∝). Theoretical analysis indicates that Pb and Ge-based 2D perovskites are significantly more thermodynamically stable than their corresponding 3D materials. A more accurate bandgap is achieved using the HSE06 + SOC scheme and compared to the findings of the PBE and PBE + SOC. These materials are direct bandgap semiconductors. Due to spin-orbit coupling, Pb-based perovskite displays higher Rashba energy splitting than Ge-based ones. The bandgap changes from 2.37 eV (n = 1) to 1.79 eV (n = 5), and from 1.92 eV (n = 1) to 1.56 eV (n = 5) for Pb and Ge-based perovskites, respectively. The bandgap of all Ge-based perovskites is lower than their corresponding Pb-based ones. We show that the 2D perovskites could serve as hole-transporting materials when they are alongside 3D perovskites. The trade-off between thermodynamic stability and absorption coefficient of the considered compounds indicates that 2D RP perovskites BA2MA4Ge5I16 are promising Pb-free halide semiconductors for solar cell applications.

Synthesis of manganese-incorporated polycaplactone-poly (glyceryl methacrylate) theranostic smart hybrid polymersomes for efficient colon adenocarcinoma treatment.

In the current study, a multifunctional nanoscale vesicular system (polymersome) with the ability to accumulate in the site of action, control drug release and integrate diagnostic and therapeutic functions was developed. The theranostic polymersome was engineered as a promising dual-functional nanoplatform, which can be used for tumor therapy and magnetic resonance imaging (MRI). In this regard, the amphiphilic diblock copolymer of poly(ε-caprolactone)-block-poly(glyceryl methacrylate)[(PCL-b-PGMA)] was synthesized by combined ring-opening polymerization (ROP), and reversible addition-fragmentation chain-transfer (RAFT) polymerization techniques followed by hydrolysis of the pendant oxiran rings to hydroxyl groups. Because of the amphiphilic properties and desirable hydrophobic/hydrophilic balance of the synthesized copolymer, it could self-assemble to form a polymersomal structure in an aqueous environment (with diameters about 100-145 nm). The hydrophilic anticancer drug, doxorubicin (DOX) and hydrophobic paramagnetic Mn (phenanthroline)2 complex, being well-represented on T1-weighted magnetic resonance imaging (MRI), were encapsulated in the hydrophilic core (33%±2.3 efficiency) and hydrophobic bilayer membrane (100 %efficient) of a polymersome system, respectively to provide PCL-PGMA@Mn(phen)2/DOX NPs. It was found that adding aptamer AS1411 to NPs surfaces enhanced their specificity and selectivity towards colorectal cancer cells expressing nucleolin (HT29 and C26). In vivo evaluation after intravenous administration of the prepared platform was performed using subcutaneous C26 tumor-bearing Balb/C mice. The obtained results demonstrated that the prepared targeted platform provided a reduced systemic toxicity in terms of body weight loss and mortality while showing efficient tumor regression. Furthermore, the prepared theranostic platform afforded MRI imaging capability for tumor monitoring. It could be concluded that the biocompatible PCL-PGMA magnetic DOX-loaded polymersomes could serve as a versatile multifunctional system for simultaneous tumor imaging and therapy.

Identification of the Most Common Allergens of Acer velutinum Pollen.

Pollens have been identified as potent inducers of allergic diseases worldwide. Acer velutinum (Persian maple) tree is an important source of allergic pollens in Iran. This study aimed to identify the immunoglobulin E (IgE)-reactive components of A. velutinum pollen extract in patients with maple allergy. We aimed to evaluate its allergenic components; using IgE in the serum of patients with maple allergy. Twenty-two patients with a clinical history of reaction and a positive skin-prick test to maple pollen extract were included in this study. Identification of IgE-binding proteins in A. velutinum pollen extract was performed by immunoblotting using sera from sensitive patients. A protein band with a molecular weight of around 70 kDa was the most IgE-reactive allergen in A. velutinum pollen extract detected by this method. Identification of a protein with a molecular weight of about 70kDa, as the most reactive allergen of A. velutinum pollen extract, can be considered as a potential allergen for designing diagnostic kits or as a target for immunotherapy of allergic patients with maple allergy.

The Effect of COVID-19 Pandemic on Patients with Primary Immunodeficiency: A Cohort Study.

Both adaptive and innate immune responses are essential for an effective defense against the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with primary immunodeficiency (PID). This study was performed on patients who were diagnosed with PID by immunologist specialists and referred to Imam Reza Clinic of Asthma and Allergy, affiliated with Shiraz University of Medical Sciences, (Shiraz, Iran) for regular check-ups. The patients were enrolled in this cohort study and followed for any sign of COVID-19 from March 2020 to May 2021. COVID-19 infection was confirmed using a real-time polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Among the 90 PID patients under study, nine patients (10%) were diagnosed positive for COVID-19 infection. Five out of these nine patients belonged to the combined immunodeficiency (CID) category, while four patients were categorized as having primary antibody deficiencies (PADs). Eight patients with COVID-19 were required to be admitted to the hospital, and three patients died after hospitalization due to COVID-19 infection. It seems that patients with CID are at a higher risk of mortality, due to COVID-19 infection, that other types of PID.

Fabrication of anionic dextran-coated micelles for aptamer targeted delivery of camptothecin and survivin-shRNA to colon adenocarcinoma.

In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

The Non-Significant Benefit of BCG Vaccination for the Treatment of Iranian Patients with Type 1 Diabetes up to 48 Weeks: A Controversial Result.

Background:There has been considerable interest in target immunotherapy in patients with diabetes. This study was designed to identify the effect of BCG vaccination in the treatment of Iranian patients with longstanding diabetes mellitus type 1. Methods: After approval of the cross-sectional study protocol by the ethics committee under number IRCT2017042919940N2, a total of 19 Iranian volunteers with diabetes mellitus type 1 completed this 48-month study. These patients received three 0.1 ml intradermal injections of BCG vaccination in weeks 0, 4 and 24. The serum level of glucose, HgbA1C and c-peptide was measured before and serially after the interventions. Insulin requirements were recorded for each patient in different weeks as the mean and standard deviation. Results: This study showed a decrease in the blood sugar level of 171.15±75.54 mg/dL in baseline to 133.77±76.97 mg/dL in 12 weeks after the first dose of BCG vaccination in these patients. There was no significant change in the mean± SD of serum blood sugar, HgbA1C and c-peptide after BCG vaccination in the baseline and week 48. Conclusion: Our results showed that small doses of BCG vaccination were not effective in long-term treatment of Iranian patients with diabetes mellitus type 1 up to 48 weeks.

Fabrication of deferasirox-decorated aptamer-targeted superparamagnetic iron oxide nanoparticles (SPION) as a therapeutic and magnetic resonance imaging agent in cancer therapy.

In the current study, the synthesis of a theranostic platform composed of superparamagnetic iron oxide nanoparticles (SPION)-deferasirox conjugates targeted with AS1411 DNA aptamer was reported. In this regard, SPION was amine-functionalized by (3-aminopropyl)trimethoxysilane (ATPMS), and then deferasirox was covalently conjugated onto its surface. Finally, to provide guided drug delivery to cancerous tissue, AS1411 aptamer was conjugated to the complex of SPION-deferasirox. The cellular toxicity assay on CHO, C-26 and AGS cell lines verified higher cellular toxicity of targeted complex in comparison with non-targeted one. The evaluation of in vivo tumor growth inhibitory effect in C26 tumor-bearing mice illustrated that the aptamer-targeted complex significantly enhanced the therapeutic outcome in comparison with both non-targeted complex and free drug. The diagnostic capability of the prepared platform was also evaluated implementing C26-tumor-bearing mice. Obtained data confirmed higher tumor accumulation and higher tumor residence time for targeted complex through MRI imaging due to the existence of SPION as a contrast agent in the core of the prepared complex. The prepared multimodal theranostic system provides a safe and effective platform for fighting against cancer.

Five new complexes with deferiprone and N,N-donor ligands: evaluation of cytotoxicity against breast cancer MCF-7 cell line and HSA-binding determination.

In this study, five new complexes containing deferiprone (dfp) and N,N-donor ligands [bipyridine (bpy), 1,10-phenanthroline (phen) and ethylenediamine (en)] were synthesized: [Fe(dfp)2(bpy)](PF6) (1), [Fe(dfp)2(phen)](PF6) (2), [Cu2(dfp)2(bpy)2](PF6)2 (3), [Ga(dfp)2(bpy)](PF6) (4), and [Fe(dfp)2(en)](PF6) (5). Characterization of these complexes was carried out through elemental analysis and FT-IR, and single-crystal X-ray crystallography was used to determine their structures. Whilst the polyhedron has a distorted octahedral geometry in 1, 2, 4, and 5, it adopts a distorted square-pyramidal geometry in 3. Interaction of these compounds with human serum albumin (HSA) has been investigated through electronic absorption and fluorescence titration techniques. Emission quenching was performed separately for each complex at three different temperatures and thermodynamic parameters were calculated using binding constants to better understand the power of different binding forces with the HSA. Results demonstrated that compounds interact strongly with the HSA with a static quenching mechanism. Our evaluation of the cytotoxicity of complexes against the breast cancer MCF-7 cell line showed that complex 2 presents a better cytotoxicity than the standard cis-Pt. Finally, using the AutoDock 4.2 program, simulations to analyze the mechanism of complex-HSA interactions and their binding mode were carried out. Results showed that the best binding mode is located in subdomain IB for 1, 2, and 4, in I/II for 3, and in IA/IIA for 5. Communicated by Ramaswamy H. Sarma.

Targeted rod-shaped mesoporous silica nanoparticles for the co-delivery of camptothecin and survivin shRNA in to colon adenocarcinoma in vitro and in vivo.

Simultaneous drug and gene delivery to cancer cells has been introduced to provide advantages of the synergistic effects of gene to sensitize the cancer cells to chemotherapeutic agent. In the current study, nucleolin-targeted co-delivery system, based on PEGylated rod-shaped mesoporous silica NPs was developed as a biocompatible nanocarrier for simultaneous delivery of camptothecin and survivin shRNA-expressing plasmid (iSur-DNA) to colon adenocarcinoma. The structural characterization including hydrodynamic radius and morphological characteristics of the prepared system demonstrated the mesoporous rod-shaped structure of the prepared system with 100-150 nm diameter. Camptothecin was loaded into the rod-shaped MSN NPs with encapsulation efficiency of 32%. At the next stage, the prepared camptothecin-loaded system was PEGylated and then iSur-DNA was condensed with C/P ratio of 6 to form PEG@MSNR-CPT/Sur. Then, the prepared camptothecin-iSur-DNA loaded PEGylated rod-shaped mesoporous silica NPs were tagged with AS1411 DNA aptamer (Apt-PEG@MSNR-CPT/Sur) in order to provide selective therapy against colorectal adenocarcinoma. The obtained results showed that the prepared platform controlled the release of anticancer drug, camptothecin. The experimental results indicated potent synergistic effect of iSur-pDNA and CPT in in vitro cytotoxicity, apoptosis induction and in vivo antitumor effect. In addition, tagging the system with AS1411 DNA aptamer facilitated drug uptake into nucleolin positive colorectal cancer cells leading to higher cellular toxicity and apoptosis induction in C26 cells compared to nucleolin-negative CHO cell line. Apt-PEG@MSNR-CPT/Sur system significantly supressed tumor growth rate in C26 tumor bearing mice while improving survival rate and pharmacokinetics of the platform in comparison with PEG@MSNR-CPT and PEG@MSNR-CPT/Sur. It could be concluded that the developed nucelolin targeted nanomedicine for co-delivery of camptothecin and iSur-DNA could serve as a versatile nanotherapeutic system against colorectal cancer.

Synthesis of chimeric polymersomes based on PLA-b-PHPMA and PCL-b-PHPMA for nucleoline guided delivery of SN38.

We reported SN38-loaded polymersomes formulated with amphiphilic block copolymers based on HPMA and either ε-caprolactone or lactic acid through employing ring-opening polymerization, carbodiimide chemistry and a reversible addition-fragmentation chain transfer polymerization technique. In this regard, we successfully synthesized five chimeric polymersomes based on different percentage of the synthesized copolymers. The prepared chimeric polymersomes based on PCL-b-PHPMA:PLA-b-PHPMA at ratio of 1:3 exhibited superior loading capacity in comparison with other chimeric polymersomes. In order to increase therapeutic index of the prepared systems, AS1411 aptamer was implemented as targeting ligand. In vivo study revealed that the intravenous single dose injection of targeted chimeric polymersomes to C26 tumor bearing mice had remarkable efficacy in inhibiting tumor growth. It could be concluded that the chimeric polymersomes fabricated from PCL-b-PHPMA and PLA-b-PHPMA at a ratio of 1:3 have great potential for SN38 encapsulation while providing controlled sustained release properties with targeting capability via AS1411 aptamer conjugation.

Synthesis of multimodal polymersomes for targeted drug delivery and MR/fluorescence imaging in metastatic breast cancer model.

The objective of the current study is to design and delivery of targeted PEG-PCL nanopolymersomes encapsulated with Gadolinium based Quantum Dots (QDs) and Doxorubicin (DOX) as magnetic resonance-florescence imaging and anti-cancer agent. Diagnostic and therapeutic efficiency of the prepared theranostic formulation was evaluated in vitro and in vivo. Hydrophobic QDs based on indium-copper-gadolinium-zinc sulfide were synthesized and characterized extensively. Hydrophobic QDs and hydrophilic DOX were loaded in PEG-PCL polymersomes through double emulsion method. Drug release pattern was studied in both citrate (pH 5.4) and phosphate (pH 7.4) buffer during 10 days. Both fluorescence and magnetic properties of bare QDs and prepared formulations were studied entirely. AS1411 DNA aptamer was covalently attached to the surface of polymersomal formulation in order to prepare targeted drug delivery system. Cellular cytotoxicity and cellular uptake analysis were performed in both nucleolin positive (MCF7 and 4T1) and nucleolin negative (CHO) cell lines. After in vitro evaluations, anti-tumor efficiency and diagnostic capability of the formulation was investigated in 4T1 tumor baring mice. Scanning emission electron microscopy (SEM) confirmed spherical shape and around 100 nm size of prepared formulations. Transmission electron microscopy (HRTEM) showed crystal shape of QDs with size of 2-3 nm. Drug release study obtained controlled release of encapsulated DOX and stability of formulation in physiologic condition. MTT and flow cytometry results demonstrated that AS1411 aptamer could enhance both toxicity and cellular uptake in nucleolin overexpressing cell lines (P < 0.05). Moreover, aptamer targeted formulation could increase survival rate and tumor inhibitory growth effect in 4T1 tumor baring mice (P < 0.05). Our results verify that aptamer targeted polymersomes loaded with non-toxic QDs as a diagnostic agent and DOX as an anti-cancer drug, could provide a theranostic platform with the purpose of optimization of treatment process and minimization of systemic side effects.

Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery.

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.

PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.

Prostate cancer (PCa) is one of the most prevalent non-drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self-assembled based on PEG-PLA nanoparticles (PEG-PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate-specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti-proliferation of drugs-loaded PEG-PLA NPs and ACUPA-PEG-PLA against LNCaP (PSMA+ ) and PC3 (PSMA- ) cells. PEG-PLA NPs with an average size of 130-140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA-modified PEG-PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA-conjugated PEG-PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer-targeting PSMA that suffer from short circulation half-life and limited therapeutic efficacy.

Hybrid silica-coated Gd-Zn-Cu-In-S/ZnS bimodal quantum dots as an epithelial cell adhesion molecule targeted drug delivery and imaging system.

Dual-modal imaging probes based on fluorescence (FL) and magnetic resonance (MR) modalities have attracted great attention due to their ability to combine the target specificity and high penetration into body tissues. In this study, we developed a potent nanocarrier with an effective photoluminescent emission and MR imaging capacity to deliver the doxorubicin to breast cancer 4T1 cells. The nanocarrier was fabricated by coating of quantum dots (QDs) with mesoporous silica followed by amine functionalization of the silica surface. Then, the doxorubicin was loaded into the silica pores and biheterofunctional PEG was covalently bound to the surface of core-shell quantum dot mesoporous silica nanoparticles. In order to target the DOX-loaded nanoparticles, the EpCAM DNA aptamer was attached on the surface of the DOX-loaded PEGylated nanoparticles. The synthesized NPs were analyzed for their size distribution, morphology, zeta potential and magnetic susceptibility using HRTEM, SEM and VSM analysis. The QD-encapsulated mesoporous silica revealed spherical shapes with an average particle size of 100 nm. The maximum encapsulation efficacy of doxorubicin in the silica pores was 25%. The in vitro release assessment demonstrated the pH-sensitive release of doxorubicin from the designed formulations. The in vitro cytotoxicity assays indicated that the aptamer targeted nanoparticles showed greater cytotoxicity than both non-targeted NPs and free DOX toward 4T1 and MCF-7 cell lines. The in vivo studies in 4T1 tumor-bearing Balb/c mice demonstrated that EpCAM aptamer could specifically deliver the DOX-loaded nanoparticles into the tumor tissue and cause remarkable inhibition of tumor growth as compared to non-targeted formulation and free DOX. Moreover, the in vivo MR and fluorescent imaging in 4T1 tumor-bearing mice confirmed the accumulation and residence of targeted system in tumor tissue even 24 h post-injection. This work presents a novel system for preparing bimodal imaging theranostic NPs through hybridization of silica and magnetic-fluorescent quantum dots.

Men's educational needs assessment in terms of their participation in prenatal, childbirth, and postnatal care.

BACKGROUND: Despite the importance of men's role in prenatal care and its impact on the outcome of a high-risk pregnancy, in many countries, including Iran, men are not aware of their real needs. Since the first step in designing any health plan is to identify the needs of the target population and that no program can be effective without considering the actual needs of the target group, this study aimed to identify men's educational needs for participation in prenatal, childbirth, and postnatal care. MATERIALS AND METHODS: In this descriptive cross-sectional study, 280 men were selected in Kashan city, Iran, in 2015. The sampling method was cluster sampling. The data collection tool was questionnaire designed based on Mortazavi and Simbar's studies that included demographic characteristics of the subjects (14 questions) and their educational needs in terms of the content of the training program, the training method, trainer, time, place of training, all of which were measured by Likert scale and completed by the interview. Data were analyzed by SPSS software version 16 using descriptive statistics. RESULTS: The findings showed that the mean age of the men participating in the study was 35.15 ± 5.83 years. Most men had high school education (45%). The three most important educational needs of men regarding participation in prenatal and postnatal care were maternal nutrition (87.5%), sexual health (86.8%), and warning signs during pregnancy (81.8%). Men preferred to receive information from a physician (93.2%), before pregnancy (91.8%) in healthcare centers (90%). Family was the most important source of information. CONCLUSION: According to men's suggestions, suitable educational programs must be implemented by physicians in healthcare centers in classes of preparation for labor and childbirth or during prenatal care.

Encapsulation of Thermo-responsive Gel in pH-sensitive Polymersomes as Dual-Responsive Smart carriers for Controlled Release of Doxorubicin.

In the current study, thermoresponsive poly(N-isopropylacrylamide)-doxorubicin (PNIPAM-DOX) hydrogel was synthesized and loaded into pH-responsive poly ethylene glycol)-2,4,6- trimethoxy benzylidene pentaerythritol carbonate (PEG-PTMBPEC) polymersomes in order to fabricate a smart thermo-pH stimuli responsive drug delivery system. Thermo-pH responsive polymersomal formulation of DOX revealed average size of 170 ±â€¯11.2 nm. The prepared system was loaded with PNIPAM-DOX conjugate with encapsulation efficiency of 30.80%. The in vivo release evaluation demonstrated that the DOX release from polymersomal formulation was pH-dependent, i.e. significantly faster drug release at pH 5.5and 6.5 compared to physiological pH. On the other hand, the drug release rate was significantly decreased at 37 °C due to the gelation of PNIPAM-DOX conjugate in the interior compartment of the pH-responsive polymersomes. The in vivo anti-tumor efficiency of the prepared polymersomal formulation of DOX was evaluated implementing C26 tumor-bearing mice after either intravenous (i.v.) or intratumoral (i.t.) single dose injection. The obtained results demonstrated that the prepared system significantly inhibited tumor growth rate in mice receiving single dose via either intravenous or intratumoral injection in comparison with free DOX-treatment group. Furthermore, treatment with polymersomal formulation did not cause any systematic toxicity in terms of pathological alteration of vital organs, survival rate and body weight loss. The prepared smart hydrosomal formulation significantly increased the blood half life time of drug and modified the biodistribution and pharmacokinetic parameters of formulated DOX. In this regard, thermo-pH-dual-stimuli responsive hydrosomal formulation represent a novel approach in nanomedicine development for effective cancer therapy.

Evaluation of Bremsstrahlung radiation dose in stereotactically radiocolloid therapy of cystic craniopharyngioma tumors with 32P radio-colloid.

Over 90% of craniopharyngeal brain tumors are cystic, which enables the injection of beta emitters such as phosphorus-32 (32P) radio-colloid into cysts for their treatment. The aim of this study was to evaluate the clinical and theoretical modelling of Bremsstrahlung radiation dose resulting from stereotactic radio-colloid therapy of cystic craniopharyngioma tumors with 32P. 32P radio-colloid with appropriate activity concentration was injected to a head phantom, and then the Bremsstrahlung radiation spectrum and planar images were obtained using a gamma camera. Both phantom and gamma camera were simulated using MCNPX code, and the results were compared with practical results. Bremsstrahlung radiation spectrum was measured using a handheld gamma spectrometer for two patients treated with stereotactic radio-colloid therapy with 32P in different positions and compared to Monte Carlo simulation. Results of counting and determining sensitivity coefficients in the air and the attenuating environment were obtained. Also, comparing the counting sensitivity from practical and simulation methods indicated the agreement of the data between the two methods. Comparison of the spectra from different positions around patient's head indicated the ability to use this detector to quantify the activity in the operating room. Selection of the spectrum is important in Bremsstrahlung radiation imaging. We can take advantage of spectrometry measurement using gamma camera, handheld gamma spectrometer for patient, and theoretical modeling with Monte Carlo code to evaluate radiopharmaceutical distribution, leakage, as well as estimate activity and predict therapeutic effects in other adjacent structures and ultimately optimize radio-colloid therapy in cystic craniopharyngeal patients.