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Gold nanoparticles (AuNPs) represent very attractive and promising drug delivery carriers due to their unique dimensions, adjustable surface functions, and controllable drug release. Therefore, AuNPs are used to overcome the limitations of conventional chemotherapy, for example methotrexate (Mex), one of the first-generation chemotherapy drugs for cancer treatment, whose usefulness has been restricted due to drug resistance and dose-dependent side effects. In the present study, the AuNPs drug delivery system was synthesized and loaded with technetium-99 m radiolabeled Methotrexate (99mTc-Mex) to produce new potential nanoradiopharmaceutical for tumor targeting and further imaging. The Methotrexate loaded gold nanoparticles (Mex-AuNPs) successfully prepared in small spherical particle size (20.3 nm), polydispersity index PDI ( 90 %. The preclinical biodistribution studies of 99mTc-Mex-AuNPs were performed in 3 experimental groups A (intravenous (I.V.) injected normal mice), B and C (I.V. and intratumor (I.T.) injected tumor bearing mice, respectively). The 99mTc-Mex-AuNPs achieved highest tumor uptake (93 ± 0.39 %ID/g) and highest Target/NonTarget (T/NT) ratio (58.1 ± 0.91) with high Tumor/Blood (T/B) ratio (25.8 ± 0.11) at 10 min post I.T. injection and retained high tumor uptake (79 ± 0.65 %ID/g) up to 60 min post I.T. injection before escaping into blood stream. Consequently, 99mTc-Mex-AuNPs can be considered as new potential nanoradiopharmaceutical in tumor diagnosis.

The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone scaffold. Nineteen compounds were proposed and docked against PNP, the best 14 compounds with highest docking and affinity scores and low RMSD values were synthesized. Synthesis of new quinazolinone derivatives with variable acetamide substituents on two positions on quinazoline ring was performed. The structures assigned to the products were concordant with the microanalytical and spectral data. In vitro cytotoxicity on human breast cancer cell line (MCF7) was performed and identified compound 6g as the most potent with IC

Nanotechnology may be applied in medicine where the utilization of nanoparticles (≤100 nm) for the delivery and targeting of theranostic agents is at the forefront of projects in cancer nano-science. This study points a novel one step synthesis approach to build up polyethylene glycol capped silver nanoparticles doped with I-131 radionuclide (131I-doped Ag-PEG NPs). The formula was prepared with average hydrodynamic size 21 nm, zeta potential - 25 mV, radiolabeling yield 98 ± 0.76%, and showed good in-vitro stability in saline and mice serum. The in-vitro cytotoxicity study of cold Ag-PEG NPs formula as a drug carrier vehicle showed no cytotoxic effect on normal cells (WI-38 cells) at a concentration below 3 μL/104 cells. The in-vivo biodistribution pattern of 131I-doped Ag-PEG NPs in solid tumor bearing mice showed high radioactivity accumulation in tumor tissues with maximum uptake of 35.43 ± 1.12 and 63.8 ± 1.3% ID/g at 60 and 15 min post intravenous (I.V.) and intratumoral injection (I.T.), respectively. Great potential of T/NT ratios were obtained throughout the experimental time points with maximum ratios 45.23 ± 0.65 and 92.46 ± 1.02 at 60 and 15 min post I.V. and I.T. injection, respectively. Thus, 131I-doped Ag-PEG NPs formulation could be displayed as a great potential tumor nano-sized theranostic probe.

Selenium is one of the most important dietary supplements in the human diet. It is incorporated into the synthesis of many antioxidant proteins, which serve as scavengers of reactive oxygen species such as glutathione peroxidase. Therefore, selenium has become antagonistic and resistant to many diseases resulting from oxidative stress such as arthritis, tumors, and heart and brain diseases. Selenium nanoparticles (SeNPs) have the potential to serve as new nutritional supplements with higher degradability, lower toxicity and ability to be cleared gradually from the body. Selenium nanoparticles have emerged as unusual selenium species with amazing prophylactic and therapeutic properties with dual synergistic effects of providing therapeutic cargo and improved anticancer activity. Recent investigations have also explored new applications of nano-scaled forms of selenium for a wide range of biological activities such as antibacterial and antifungal agents. Herein, we provide a focused account on the recent advances on various biomedical applications of selenium nanoparticles with a particular emphasis on their chemistry, nanotechnology and various applications in life sciences.

The purpose of our investigation was to promote the bioavailability and the brain delivery of rivastigmine tartarate (RV) through optimization of mucoadhesive thermosensitive in situ gel via intranasal (IN) route. The mucoadhesive in situ gels were developed using pluronic F127 (PF127) as thermogelling agent and different mucoadhesive polymers. A full factorial design was implemented to study the influence of three factors; pluronic type at two levels (PF127, PF127/PF68), mucoadhesive polymer type at four levels (HPMC, Chitosan, Carbopol 934 and NaCMC) and mucoadhesive polymer concentration at two levels (0.5 and 1%w/v). The studied responses were sol-gel temperature, consistency, gel strength, adhesion work and T50% of drug release. In vivo pharmacokinetic and biodistribution studies of the selected formula were investigated using radiolabeling approach using normal albino mice. The optimal RV in situ gel (PF127 and 1% Carbopol 934) showed significant transnasal permeation (84%) which was reflected in better distribution to the brain (0.54 %ID/g), when compared to RV IN solution (0.16 %ID/g) and RV IV intravenous solution (0.15 %ID/g). In conclusion, the investigated results showed the potential use of mucoadhesive in situ gel as a promising system for brain targeting of RV via the transnasal delivery system.

Stem cells are undifferentiated cells with a potential to be developed into different types of body cells. Stem cells are used in regenerative medicine as a repair system that is working to restore the structures and functions of damaged tissues and organs aiming to find a way to cure untreatable injuries and diseases. Stem cell-nanotechnology hybrid is the application of nanotechnology in stem cells research. One of the most interesting applications is the biocompatible magnetically-responsive nanoparticles (NP) that are being utilized for the targeted delivery of stem cells; in order to enhance their retention in the desired treatment site. This review provides an overview of stem cells therapy based on nanotechnology for the treatment of different diseases, such as: peripheral artery disease (PAD), myocardial infarction (MI), atherosclerosis, Huntington's disease, spinal cord injury (SCI), Alzheimer disease (AD), diabetes mellitus (DM), multiple sclerosis (MS), erectile dysfunction (ED), and cancer diseases.

Nanostructured materials attracted considerable attention because of its high surface area to volume ratio resulting from their nano-scale dimensions. This class of sorbents is expected to have a potential impact on enhancement the efficacy of radioisotope generators for diagnostic and therapeutic applications in nuclear medicine. This review provides a summary on the importance of nanostructured materials as effective sorbents for the development of clinical-scale radioisotope generators and outlining the assessment of recent developments, key challenges and promising access to the near future.

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal cancer cell line (Caco-2). All the synthesized compounds showed better activity than the reference standards (Doxorubicin and 5-FU). Investigation of the apoptotic activity of the most active compounds revealed that compounds 3a, 5a, 5c and 6c activate both caspase-3 and Fas-ligand in Caco-2 cell line. Compound 3a was the most active compound with caspase-3 concentration of 0.43 nmol/mL and Fas-ligand concentration of 775.2 pg/mL in treated Caco-2 cells. Compound 3a was radiolabeled with 99mTc and its biodistribution pattern was evaluated in vivo using normal Swiss Albino mice. 99mTc-compound 3a complex didn't exhibit any accumulation in any body organs except for its accumulation in the colon; target organ; where it showed 8.97 ± 1.35 %ID/g at 15min p. i. that elevated till 16.02 ± 2.43 %ID/g at 120min p. i.

Early and accurate detection of tumor assists in identifying more effective therapies. Gold nanoparticles (GNPs) were synthesized by green synthesis method using gallic acid (GA) then characterized and labeled with technetium-99m. This new platform was biologically evaluated in both normal and solid tumor bearing mice. The in-vivo study of [99mTc]Tc-gallic-GNPs via both I.V. and I.T injecton showed a high accumulation in tumor site. As a result, [99mTc]Tc-gallic-GNPs can be afforded as a potential nano-platform for tumor imaging.

The development of cancer theranostic nanomedicines is recommended to concurrently achieve and evaluate the therapeutic benefit and progress. The current work aims to develop gallic acid-gold nanoparticles (GA-Au NPs) as a theranostic probe for 99mTc-Doxorubicin (99mTc-DOX) based on the spatiotemporal release pattern induced intra-tumoral (IT) delivery. DOX-loaded GA-Au NPs were developed and identified via UV–Vis spectroscopy. The system was characterized for drug loading efficiency%, particle size, zeta potential, topography, in vitro DOX release and anti-proliferative activity against the MCF-7 cell-line. The factors influencing radiolabeling efficiency of DOX with 99mTc (DOX concentration, stannous chloride concentration, reaction time and pH) were optimized. The in vitro stability in mice serum and in vivo distribution studies in mice of 99mTc-DOX-loaded GA-Au NPs were investigated following IV and IT administration. Dox-loaded GA-Au NPs had a loading efficiency of 91%, a small particle size (≈50 nm), a promising zeta potential (−20 mV) and a sustained drug release profile at pH 5.3. GA-Au NPs exhibited increased anti-proliferative activity, with approximately a four-fold lower IC50 value (0.15 μg/ml) than free DOX. The optimized radiolabeling efficiency of 99mTc-DOX was ≈93%. It showed good physiological stability in mice serum for at least 8 h. The IT delivery of 99mTc-DOX-loaded GA-Au NPs in tumor-induced mice showed dramatic tumor accumulation. A maximum magnitude of 86.73%ID/g was achieved, at 15 min post-injection, with a target/non-target ratio of ≈56. 99mTc-DOX-loaded GA-Au NPs could be used for the selective IT delivery of a chemotherapeutic agent and an imaging agent to a target organ.

New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for 99mTc that showed a remarkable uptake and targeting ability towards the infection site that was induced in mice.

Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with 99m Tc) with high in silico affinity. The novel prepared 99m Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors . 99m Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7 ± 3.25). It showed in vitro stability for up to 6 h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60 min post-injection. The data described previously could recommend 99m Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging.

Bisphosphonates are widely used for treatment of osteoporosis. Recently, they have been reported to be effective anticancer agents. In this work, we designed some substituted phenyl (azanediyl) bis (methylene phosphonic acid) to be tested for their anticancer effect. Both molecular docking and dynamics studies were used to select the top ranked highly scored compounds. The selected hits showed potential in vitro anticancer effect against some cell lines. Biodistribution pattern and gamma scintigraphy were conducted to the most effective derivative (BMBP) after radiolabeling with 99mTc. Results of biodistribution and scintigraphic imaging of 99mTc-BMBP in tumor bearing mice showed a notable tumor affinity, and confirmed the targeting affinity of BMBP to the tumor tissues. As a conclusion, BMBP could act as potential anticancer agent and imaging probe.

Zirconium molybdate gel was prepared by mixing (99)Mo, produced from (98)Mo(n,gamma) reaction and Zr solutions in nitrate media with excess H(2)O(2), and used as the base material for (99)Mo/(99m)Tc generator. The prepared generator showed a good performance. (99m)Tc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The (99m)Tc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. (99m)Tc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95+/-2% by adding (99m)Tc to 30 mg ceftriaxone in the presence of 50 microg SnCl(2).2H(2)O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. (99m)Tc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6+/-0.6 at 4h post injection). The abscess to normal muscle ratio indicated that (99m)Tc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that (99m)Tc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.