Comparison of Selenic Acid and Pyruvic Acid-Loaded Silver Nanocarriers Impact on Colorectal Cancer Viability.

Colorectal cancer (CRC) is a leading cause of morbidity and death worldwide. As current cancer drugs are ineffective, new solutions are being sought in other fields, including nanoscience. Similarly, silver nanoparticles play an important role in the pharmaceutical industry as they act as anti-cancer agents with less harmful effects and are usually 1 to 100 nm in size. Selenic acid (SA) and pyruvic acid (PA) are involved in various metabolic pathways in cancer. For this reason, we decided to detect their influence on colorectal cancer using silver-based (Ag) nanocarriers. DLS, Zetasizer, SEM and UV-Vis analyses were used to characterize AgSA and AgPA. A UV spectrophotometer was used to analyze the release of the NPs. MTT analyses were used to measure the viability of HCT116 and HUVEC cells, and IC50 values were calculated using GraphPad Prism. The indicated dosage and particle size of AgSA NPs proved to be suitable for cytotoxicity. Moreover, injection of these nanoparticles into non-cancer cells proved safe due to their minimal toxicity. In contrast, the AgPA NPs have no cytotoxicity and induce proliferation of HCT116 cells. Finally, only the synthesised AgSA nanoparticles could be used for advanced cancer therapy, which is both inexpensive and has minimal side effects.

Poly(L-lactic acid)/poly(ethylene oxide) based composite electrospun fibers loaded with magnesium-aluminum layered double hydroxide nanoparticles.

Two types of MgAl layered double hydroxide nanoparticles, MgAl LDH, at Mg:Al ratio of 2:1 and 3:1were prepared and used as inorganic fillers to improve the mechanical properties of poly(lactic acid)/poly(ethylene oxide) (PLA/PEO) electrospun composite fibers. Their detailed structural characterization was performed using X-ray diffraction (XRD) and transmission electron spectroscopy (TEM) techniques. Spectroscopic, thermal, mechanical, and morphological properties of the electrospun composite fibers, and cell proliferation on their surface, were examined. XRD and TEM analyses showed that the LDH nanoparticles were 50 nm in size and the Mg:Al ratio did not affect the average spacing between crystal layers. Fourier transform infrared (FTIR) and thermal analyses (TA) revealed the compatibility of the filler and the polymer matrix. The nanoparticles considerably improved the mechanical properties of the electrospun mats. The tensile strength and elongation at break values of the composite samples increased from 0.22 MPA to 0.40 MPa and 12.2 % to 45.66 %, respectively, resulting from the interaction between LDH and the polymer matrix. Scanning electron microscopy (SEM) and MTT analyses demonstrated that the electrospun composite fibers supported the SaOS-2 cells attachment and proliferation on the fiber surfaces, along with their suitable cytocompatibility.

Evaluation of anticancer effects of carboplatin-gelatin nanoparticles in different sizes synthesized with newly self-assembly method by exposure to IR light.

Carboplatin (CP), a platinum analog, is one of the most widely used chemotherapeutic agents in the treatment of colorectal cancer. Although platinum-based drugs are quite effective in anticancer treatments, their use in a wide spectrum and effective treatment possibilities are limited due to their systemic side effects and drug resistance development. In recent years, studies have focused on increasing the therapeutic efficacy of platinum-based drugs with drug delivery systems. Gelatin, a protein, obtained by the hydrolysis of collagen, is a biocompatible and biodegradable material that can be used in nano drug delivery systems. In this study, CP-loaded gelatin-based NPs (CP-NPs) were exposed to IR light in different temperatures at 30, 35, 40, 45, and 50 °C and characterized by FESEM-EDX, FTIR, UV-Vis, DLS. Accordingly, we synthesized gelatin-based CP-NPs of different sizes between 10-290 nm by exposure to IR. We found that CP-NPs-50, 16 nm nano-sized, obtained at 50 °C had the most cytotoxicity and was 2.2 times more effective than the free drug in HCT 116 colon cancer cells. Moreover, we showed that the cytotoxicity of CP-NPs-50 in normal HUVEC cells was lower. Additionally, we demonstrated that CP-NPs enhanced apoptotic activity while not developing MDR1-related resistance in colon cancer cells. In this study, for the first time drug loaded gelatin-based nanoparticles were synthesized in different sizes with a newly self-assembly method by exposing them to infrared light at different temperatures and their anticancer effects were evaluated subsequently.

Development and In Vitro Evaluation of Biocompatible PLA-Based Trilayer Nanofibrous Membranes for the Delivery of Nanoceria: A Novel Approach for Diabetic Wound Healing.

The attempts to explore and optimize the efficiency of diabetic wound healing's promotors are still in progress. Incorporation of cerium oxide nanoparticles (nCeO2) in appropriate nanofibers (NFs) can prolong and maximize their promoting effect for the healing of diabetic wounds, through their sustained releases, as well as the nanofibers role in mimicking of the extra cellular matrix (ECM). The as-prepared nCeO2 were analyzed by using UV-Vis spectroscopy, XRD, SEM-EDX, TEM and FTIR, where TEM and SEM images of both aqueous suspension and powder showed spherical/ovoid-shaped particles. Biodegradable trilayer NFs with cytobiocompatibility were developed to sandwich nCeO2 in PVA NFs as a middle layer where PLA NFs were electrospun as outer bilayer. The nCeO2-loaded trilayer NFs were characterized by SEM, XRD, FTIR and DSC. A two-stage release behavior was observed when the nanoceria was released from the trilayer-based nanofibers; an initial burst release took place, and then it was followed by a sustained release pattern. The mouse embryo fibroblasts, i.e., 3T3 cells, were seeded over the nCeO2-loaded NFs mats to investigate their cyto-biocompatibility. The presence and sustained release of nCeO2 efficiently enhance the adhesion, growth and proliferation of the fibroblasts' populations. Moreover, the incorporation of nCeO2 with a higher amount into the designed trilayer NFs demonstrated a significant improvement in morphological, mechanical, thermal and cyto-biocompatibility properties than lower doses. Overall, the obtained results suggest that designated trilayer nanofibrous membranes would offer a specific approach for the treatment of diabetic wounds through an effective controlled release of nCeO2.

Mechanical and Biocompatibility Properties of Calcium Phosphate Bioceramics Derived from Salmon Fish Bone Wastes.

Natural calcium phosphates derived from fish wastes are a promising material for biomedical application. However, their sintered ceramics are not fully characterized in terms of mechanical and biological properties. In this study, natural calcium phosphate was synthesized through a thermal calcination process from salmon fish bone wastes. The salmon-derived calcium phosphates (sCaP) were sintered at different temperatures to obtain natural calcium phosphate bioceramics and then were investigated in terms of their microstructure, mechanical properties and biocompatibility. In particular, this work is concerned with the effects of grain size on the relative density and microhardness of the sCaP bioceramics. Ca/P ratio of the sintered sCaP ranged from 1.73 to 1.52 when the sintering temperature was raised from 1000 to 1300 °C. The crystal phase of all the sCaP bioceramics obtained was biphasic and composed of hydroxyapatite (HA) and tricalcium phosphate (TCP). The density and microhardness of the sCaP bioceramics increased in the temperature interval 1000-1100 °C, while at temperatures higher than 1100 °C, these properties were not significantly altered. The highest compressive strength of 116 MPa was recorded for the samples sintered at 1100 °C. In vitro biocompatibility was also examined in the behavior of osteosarcoma (Saos-2) cells, indicating that the sCaP bioceramics had no cytotoxicity effect. Salmon-derived biphasic calcium phosphates (BCP) have the potential to contribute to the development of bone substituted materials.

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study.

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging.

Indocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named "therapeutic window" in the tissue engineering. Unfortunately, rapid elimination and short-term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l-lactic acid) and poly(ε-caprolactone) via a simple one-step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa-2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG-encapsulated multiaxial nanofiber mats. ICG-encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG-loaded nanoparticles in systemic administration.

Characterization and Isolation of Very Small Embryonic-like (VSEL) Stem Cells Obtained from Various Human Hematopoietic Cell Sources.

Stem cell transplantation is one of the available treatments for leukemia, lymphoma, hereditary blood diseases and bone marrow failure. Bone marrow (BM), peripheral blood progenitor cells (PBPC), and cord blood (CB) are the predominant sources of stem cells. Recently a new type of stem cell with a pluripotent potential has been identified. These cells were named "very small embryonic like stem cells (VSELs)". It is claimed that VSEL stem cells can be found in adult BM, peripheral blood (PB), CB and other body tissues. This study is designed to characterize and isolate VSEL stem cells from different human hematopoietic sources; CB, PB and apheresis material (PBPC). VSEL stem cells were isolated from MNC and erythrocyte layers for all materials by using centrifugation and ficoll gradient method. We determined embryonic markers by flow cytometry, immunofluorescence and western blotting methods. Results from western blotting and immunofluorescence show high level of NANOG and OCT4 protein expression in PB, apheresis material and CB. Immunofluorescence images showed cytoplasmic and nuclear presence of these proteins. Flow cytometry results exhibited a higher expression of VSELs markers on debris area than CD45- population and higher expression on CB than PB. As a result, these findings have shown that it is necessary to investigate the function of pluripotent stem cell markers in differentiated adult cells. We further conclude that erythrocyte lysis method had the highest cell recovery amount among erythrocyte lysis and ficoll gradient methods. Consequently, this study gives us new information and viewpoints about expression of pluripotent stem cell (PSC) markers in adult tissues.