Drug Delivery Using Hydrophilic Metal-Organic Frameworks (MOFs): Effect of Structure Properties of MOFs on Biological Behavior of Carriers.

To study the influence of pore structural properties of metal-organic frameworks (MOFs) on drug adsorption and delivery, we synthesized two MOF termed TMU-6(RL1) {[Zn(oba)(RL1)0.5]n·(DMF)1.5} and TMU-21(RL2) {[Zn(oba)(RL2)0.5]n·(DMF)1.5} with amine basic N-donor pillars containing phenyl or naphthyl cores with various hydrophilic properties around the main center of the reaction. TG, IR, XPS, and PXRD analyses were used to extensively characterize the MOFs. The synthesized carriers showed high adsorption efficiency, stability, and controlled release. As an anticancer drug, Nimesulide (Nim) was adsorbed to MOFs using multiple adsorption mechanisms, such as Hostπ-πGuest interaction and HostN-H···OGuest hydrogen bonds. Moreover, Hirshfeld surface analysis showed when the benzene core was replaced with the naphthalene core, the percentage of intermolecular interactions of π···π and N···H by amine sites in TMU-21(RL2) decreased compared with TMU-6(RL1), while the percentage of these interactions with guest molecules increased. The results showed that changes in the hydrophobicity/hydrophilicity properties of MOFs would alter their ability to adsorb Nim in the pore of the frameworks. In vitro anticancer studies also showed that the cytotoxicity of Nim in MOFs@Nim composites against human cervical cancer cell line (HeLa cells) and human colon cancer cell line (HT-29 cells) is much higher than that of free Nim. Generally, based on the results, it can be said that the biological behavior of carriers can be regulated by adjusting the structure properties of MOFs.

Wet-spinnability and crosslinked Fiber properties of alginate/hydroxyethyl cellulose with varied proportion for potential use in tendon tissue engineering.

Researchers have examined different bio-inspired materials in tissue engineering and regenerative medicine to fabricate scaffolds to address tendon regeneration requirements. We developed fibers based on alginate (Alg) and hydroxyethyl cellulose (HEC) by wet-spinning technique to mimic the fibrous sheath of ECM. Various proportions (25:75, 50:50, 75:25) of 1 % Alg and 4 % HEC were blended to this aim. Two steps of crosslinking with different concentrations of CaCl2 (2.5 and 5 %) and glutaraldehyde (2.5 %) were used to improve physical and mechanical properties. The fibers were characterized by FTIR, SEM, swelling, degradation, and tensile tests. The in vitro proliferation, viability, and migration of tenocytes on the fibers were also evaluated. Moreover, the biocompatibility of implanted fibers was investigated in an animal model. The results showed ionic and covalent molecular interactions between the components. In addition, by properly maintaining surface morphology, fiber alignment, and swelling, lower concentrations of HEC in the blending provided good degradability and mechanical features. The mechanical strength of fibers was in the range of collagenous fibers. Increasing the crosslinking led to significantly different mechanical behaviors in terms of tensile strength and elongation at break. Because of good in vitro and in vivo biocompatibility, tenocyte proliferation, and migration, the biological macromolecular fibers could serve as desirable tendon substitutes. This study provides more practical insight into tendon tissue engineering in translational medicine.

Anti-cancer effects of human placenta-derived amniotic epithelial stem cells loaded with paclitaxel on cancer cells.

Available therapeutic strategies for cancers have developed side effects, resistance, and recurrence that cause lower survival rates. Utilizing targeted drug delivery techniques has opened up new hopes for increasing the efficacy of cancer treatment. The current study aimed to investigate the appropriate condition of primming human amniotic epithelial cells (hAECs) with paclitaxel as a dual therapeutic approach consisting of inherent anticancer features of hAECs and loaded paclitaxel. The effects of paclitaxel on the viability of hAECs were evaluated to find an appropriate loading period. The possible mechanism of hAECs paclitaxel resistance was assessed using verapamil. Afterward, the loading and releasing efficacy of primed hAECs were evaluated by HPLC. The anti-neoplastic effects and apoptosis as possible mechanism of conditioned media of paclitaxel-loaded hAECs were assessed on breast and cervical cancer cell lines. hAECs are highly resistant to cytotoxic effects of paclitaxel in 24 h. Evaluating the role of P-glycoproteins in hAECs resistance showed that they do not participate in hAECs resistance. The HPLC demonstrated that hAECs uptake/release paclitaxel with optimum efficacy in 8000 ng/ml treatment. Assessing the anti-proliferative effect of primed hAECs condition media on cancer cells showed that the secretome induced 3.3- and 4.8-times more potent effects on MCF-7 and HeLa, respectively, and enhanced the apoptosis process. These results suggest that hAECs could possibly be used as a drug delivery system for cancer treatment. Besides, inherent anticancer effects of hAECs were preserved during the modification process. Synergistic anticancer effects of paclitaxel and hAECs can be translated into clinical practice, which would be evaluated in the future studies.

Fabrication of nanochitosan incorporated polypyrrole/alginate conducting scaffold for neural tissue engineering.

The utilization of conductive polymers for fabrication of neural scaffolds have attracted much interest because of providing a microenvironment which can imitate nerve tissues. In this study, polypyrrole (PPy)-alginate (Alg) composites were prepared using different percentages of alginate and pyrrole by oxidative polymerization method using FeCl3 as an oxidant and electrical conductivity of composites were measured by four probe method. In addition, chitosan-based nanoparticles were synthesized by ionic gelation method and after characterization merged into PPy-Alg composite in order to fabricate a conductive, hydrophilic, processable and stable scaffold. Physiochemical characterization of nanochitosan/PPy-Alg scaffold such as electrical conductivity, porosity, swelling and degradation was investigated. Moreover, cytotoxicity and proliferation were examined by culturing OLN-93 neural and human dermal fibroblasts cells on the Nanochitosan/PPy-Alg scaffold. Due to the high conductivity, the film with ratio 2:10 (PPy-Alg) was recognized more suitable for fabrication of the final scaffold. Results from FT-IR and SEM, evaluation of porosity, swelling and degradation, as well as viability and proliferation of OLN-93 neural and fibroblast cells confirmed cytocompatiblity of the Nanochitosan/PPy-Alg scaffold. Based on the features of the constructed scaffold, Nanochitosan/PPy-Alg scaffold can be a proper candidate for neural tissue engineering.

Purified compounds from marine organism sea pen induce apoptosis in human breast cancer cell MDA-MB-231 and cervical cancer cell Hela.

Marine organisms are an important source of chemical compounds which are appropriate for use as therapeutic agents. Among them, Sea pens produce valuable chemical compounds being used as anti-cancer drugs. The aim of this study was to investigate anti-cancer property of extracted and purified compounds from marine organism Sea pen and evaluate their effects on inducing of apoptosis. The extracts were prepared from dried colony of Virgularia gustaviana. The compounds (3ß)-Cholest,5en,3ol (cholesterol) (15 mg), Hexadecanoic acid (2.5 mg) and 2-Hexadecanol (10.7 mg) were identified by GC-MS and NMR. The cytotoxic effects of the compounds were evaluated on Hela and MDA-Mb-231 human cancer cell lines with MTT assay. Immunocytochemistry and Western Blot analyses were used to evaluate the expression of apoptosis related markers Caspase 3, Caspase 8, Bax and BCL2 in cancer cells after treating with three compounds. The purified compounds reduced viability of human breast cancer cell line MDA-MB-231 and human cervical cancer cell line Hela concentration-dependently. 2-Hexadecanol reduced significantly the viability of both cancer cell lines in comparison to the other purified compounds. Treatment of cancer cells with the three purified compounds increased the expression of caspase-3, caspase-8 and Bax proteins and decreased the relative Bcl-2/Bax ratio, demonstrating induction of apoptosis as possible mechanism of action. According to the results, three purified compounds inhibit the growth of cancer cells by inducing of apoptosis pathway; an effect which needs to be further investigated in the future studies.