Co-delivery of carboplatin and doxorubicin using ZIF-8 coated chitosan-poly(N-isopropyl acrylamide) nanoparticles through a dual pH/thermo responsive strategy to breast cancer cells.

A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.6 % and 55.54 %, respectively. NPs showed a pH and thermoresponsive drug release profile with a sustained prolonged release under physiological conditions. The in vitro cytotoxicity experiments showed a significant synergism of CBP and DOX to induce the IC50 of 1.96 µg/mL in MCF-7 cells and 4.54 µg/mL in MDA-MB-231 cells. Also, the final NPs were safer than free DOX and CBP on normal cells. The in vitro study confirmed the higher potency of the designed NPs in combination therapy against breast cancer cells with lower side effects than free drugs.

Clinical Outcomes and Effectiveness of CRLX101 for Solid Tumors: A Systematic Review and Meta-analysis.

BACKGROUND: While it has been demonstrated that delivery of cytotoxic chemotherapy using nanoparticles greatly improves patient drug tolerance and reduces toxicity when compared to the standard formulation, the crucial question of whether they also increase anticancer efficacy remains. The CRLX101 is a nanoparticle composed of cyclodextrin and 20(S)-camptothecin cytotoxic chemotherapy. OBJECTIVE: In order to compare the efficacy of the CRLX101 to its corresponding traditional formulation, we carried out this systematic literature search for randomized clinical and non-randomized trials. METHODS: Multiple electronic databases, including PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and clinicaltrials.gov, were used to conduct a thorough literature search. By employing a technique akin to a random-effects model, the median of the study-specific was taken into account as the pooled median estimate with a 95% confidence interval. RESULTS: Finally, nine clinical studies were chosen for the meta-analysis. The treatment and control groups' overall survival were examined in five and three trials, respectively. Additionally, six out of nine trials and two out of nine trials, respectively, examined the treatment and control groups for progression-free survival (PFS). Meta-analysis revealed that the treatment group had a lower median overall survival (OS) but a greater median progression-free survival than the control group. CONCLUSION: Our meta-analysis shows that CRLX101 outperforms camptothecin in PFS despite its inferior OS. Unresolved pharmacology limits carrier-mediated drug therapeutic application. Carrier-mediated dosages may differ from normal formulations because they are rarely studied.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. AIMS: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. MATERIALS AND METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells.

This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity. Targeted liposomes increased cytotoxicity on MCF-7 cells more significantly than NIH-3T3 cells. Cell flow cytometry indicated that targeted liposomes uptake was superior to plain (non-targted) liposomes and free drug. Free drug and RB-loaded liposomes interrupted cell cycle in G1. However, amino acid-targeted liposomes arrested cells more than the free drug at this stage. Targeted liposomes reduced cell cycle with more interruption in the G2/M phase compared to the negative control.

Keratin- and VEGF-Incorporated Honey-Based Sponge-Nanofiber Dressing: An Ideal Construct for Wound Healing.

To overcome the drawbacks of single-layered wound dressings, bilayer dressings are now introduced as an alternative to achieve effective and long-term treatment. Here, a bilayer dressing composed of electrospun nanofibers in the bottom layer (BL) and a sponge structure as the top layer (TL) is presented. Hydrophilic poly(acrylic acid) (PAAc)-honey (Hny) with interconnected pores of 76.04 µm was prepared as the TL and keratin (Kr), Hny, and vascular endothelial growth factor (VEGF) were prepared as the BL. VEGF indicates a gradual release over 7 days, promoting angiogenesis, as proven by the chick chorioallantoic membrane assay and in vivo tissue histomorphology observation. Additionally, the fabricated dressing material indicated a satisfactory tensile profile, cytocompatibility for human keratinocyte cells, and the ability to promote cell attachment and migration. The in vivo animal model demonstrated that the full-thickness wound healed faster when it was covered with PAAc-Hny/Hny-Kr-VEGF than in other groups. Additionally, faster blood vessel formation, collagen synthetization, and epidermal layer generation were also confirmed, which have proven efficient healing acceleration in wounds treated with synthesized bilayer dressings. Our findings indicated that the fabricated material can be promising as a functional wound dressing.

Enhancement of the anti-microbial activity of Mentha spicata essential oil on storage by glycerosomes.

Mentha spicata essential oil (EO) is isolated from the aerial parts of Mentha spicata L. with pronounced antibacterial effects as food preservative in food industry. Nevertheless, its application in the clinical industry and food is significantly restricted by its poor water solubility and physicochemical instability. Glycerosomes of this EO were prepared to enhance its anti-microbial stability. The EO was encapsulated in the glycerosomes and characterized for its physical properties. The optimized EO-loaded glycerosomes displayed entrapment efficiency of 93.2 ± 7.5%, release efficiency of 75.4 ± 6.1%, the particle size of 276 nm, and zeta potential of - 30.4 mV. Scanning electron microscopy (SEM) image showed spherical morphology of the glycerosomes. EO release from optimized formulation of glycerosomes best fitted with a first-order kinetic model. Compared with free EO, EO-loaded glycerosomes showed better storage stability. The results indicated that the incorporation of EO in glycerosomes possessed sustained release properties and significantly enhanced antibacterial effects in storage.

Anti HER-2 aptamer functionalized gold nanoparticles of dasatinib for targeted chemo-radiotherapy in breast cancer cells.

In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles. The loading efficiency of the activated drug on plain and porous gold nanoparticles was 52 and 68 %, respectively, which was significantly more than the loading of free DSB in gold nanoparticles (1-2.5 %). The anti HER-2 aptamer was conjugated to porous gold nanoparticles loaded with the activated drug. Various characterization techniques such as FESEM, TEM, AFM, zeta potential and ICP-MS were used to confirm the binding of the drug to gold nanoparticles. 1HNMR and FTIR spectroscopic analyses were employed to examine the structural characteristics of the conjugated drug. These analytical techniques confirmed the successful incorporation of succinyl and thiol groups onto the drug molecule. The amount of aptamer binding to different types of gold nanoparticles was obtained from the intensity of the light emitted from the bands observed in electrophoresis gel and due to the presence of porosity in porous gold nanoparticles, the amount of aptamer conjugation on porous gold nanoparticles increased compared to plain ones. Cell cytotoxicity and cellular uptake were evaluated by MTT assay and TEM in BT-474 and MCF-7 cells. Aptamer-functionalized porous gold nanoparticles containing activated dasatinib showed higher cytotoxicity and cellular uptake than modified DSB-loaded nanoparticles and un-activated DSB. The combination of radiation therapy with the modified dasatinib attached to porous gold nanoparticles and aptamer demonstrated a notable reduction in the IC50 values for both the BT-474 and MCF-7 cell lines. Specifically, the IC50 value for the BT-474 cells decreased from 6.95 µM (for unmodified dasatinib) to 2.57 µM, while for the MCF-7 cells, it decreased from 13.97 µM to 8.57 µM. These findings indicate a significant improvement in the efficacy of the modified dasatinib compared to its unmodified counterpart when used in conjunction with radiation therapy.

Gene network analysis of oxaliplatin-resistant colorectal cancer to target a crucial gene using chitosan/hyaluronic acid/protamine polyplexes containing CRISPR-Cas9.

Colorectal cancer (CRC) treatment is dramatically hampered by resistance to oxaliplatin alone or in the combination of irinotecan or 5-fluorouracil and leucovorin. This study aims to design and assess Chitosan/Hyaluronic Acid/Protamine sulfate (CS/HA/PS) polyplexes loaded with CRISPR plasmid for targeting a key gene in cancer drug resistance. Here, recent findings were considered to validate oxaliplatin-resistant CRC-related genes and systems biology approaches employed to detect the critical gene. The polyplexes were characterized according to particle size, zeta potential, and stability. Moreover, carrier toxicity and transfection efficiency were assessed on oxaliplatin-resistant HT-29 cells. The post-transfection evaluations were performed to confirm gene disruption-mediated CRISPR. Eventually, excision cross complementation group 1(ERCC1), a crucial member of the nucleotide excision repair pathway, was selected to be targeted using CRISPR/Cas9 to reverse oxaliplatin resistance in HT-29 cells. CS/HA/PS polyplexes containing CRISPR/Cas9 plasmid exhibited negligible toxicity and comparable transfection efficiency with Lipofectamine™. Following the efficient gene delivery, sequences in CRISPR/Cas9 target sites were altered, ERCC1 was downregulated, and drug sensitivity was successfully restored in oxaliplatin-resistant cells. Findings indicate that CS/HA/PS/CRISPR polyplexes provide a potential strategy for delivering cargo and targeting oxaliplatin resistance-related gene to manipulate drug resistance as a rising concern in cancer therapeutic approaches.

Asymmetric tri-layer sponge-nanofiber wound dressing containing insulin-like growth factor-1 and multi-walled carbon nanotubes for acceleration of full-thickness wound healing.

To more closely resemble the structure of natural skin, multi-layered wound dressings have been developed. Herein, a tri-layer wound dressing was prepared containing a polyacrylamide (PAAm)-Aloe vera (Alo) sponge that had been incorporated with insulin-like growth factor-1 (IGF1) to provide a porous absorbent layer, which was able to promote angiogenesis. Alo nanofibers with multi-walled carbon nanotubes (MWCNT) were electrospun into the bottom layer to increase cell behavior, and a small film of stearic acid was put as a top layer to avoid germy penetration. In comparison to bilayer dressing, the tensile strength increased by 17.0 % (from 0.200 ± 0.010 MPa to 0.234 ± 0.022 MPa) and the elastic modulus by 45.6 % (from 0.217 ± 0.003 MPa to 0.316 ± 0.012 MPa) in the presence of Alo nanofibers containing 0.5 wt% of MWCNT at the bottom layer of Trilayer0.5 dressing. The release profile of IGF1, the antibacterial activity and the degradability of different wound dressings were investigated. Trilayer0.5 indicated the highest cell viability, cell adhesion and angiogenic potential among the prepared dressing materials. In-vivo rat model revealed that the Trilayer0.5 dressing treated group had the highest rate of wound closure and wound healing within 10 days compared to other groups.

A 3D printed polylactic acid-Baghdadite nanocomposite scaffold coated with microporous chitosan-VEGF for bone regeneration applications.

Three-dimensional (3D) printing technology has become an advanced approach for fabricating patient-specific scaffolds with complex geometric shapes to replace damaged or diseased tissue. Herein, polylactic acid (PLA)-Baghdadite (Bgh) scaffold were made through the fused deposition modeling (FDM) 3D printing method and subjected to alkaline treatment. Following fabrication, the scaffolds were coated with either chitosan (Cs)-vascular endothelial growth factor (VEGF) or lyophilized Cs-VEGF known as PLA-Bgh/Cs-VEGF and PLA-Bgh/L.(Cs-VEGF), respectively. Based on the results, it was found that the coated scaffolds had higher porosity, compressive strength and elastic modulus than PLA and PLA-Bgh samples. Also, the osteogenic differentiation potential of scaffolds following culture with rat bone marrow-derived mesenchymal stem cells (rMSCs) was evaluated through crystal violet and Alizarin-red staining, alkaline phosphatase (ALP) activity and calcium content assays, osteocalcin measurements, and gene expression analysis. The release of VEGF from the coated scaffolds was assessed and also the angiogenic potential of scaffolds was evaluated. The sum of results presented in the current study strongly suggests that the PLA-Bgh/L.(Cs-VEGF) scaffold can be a proper candidate for bone healing applications.

Preparation and characterization of hydroxyapatite nanoparticles doped with nickel, tin, and molybdate ions for their antimicrobial effects.

BACKGROUND: Hydroxyapatite (HAp) nanoparticles doped with some ions have shown anticancer and antibacterial properties and are of great interest for the development of new biomedical applications. Therefore, the present study aimed to investigate the preparation and in vitro characterization of HAp nanoparticles doped with (Ni2+), tin (Sn2+), molybdate (Mo3+) ions for prevention of infections specially in bone tissue engineering. METHODS: HAp and HAp nanocrystal powders doped with nickel (Ni2+), tin (Sn2+), molybdate ions (Mo3+) with concentrations of 500, 1000, and 2000 ppm were prepared by the sol-gel method using a combination of calcium nitrate and phosphorous pentoxide as chemical reagents. The nanoparticles were characterized by FT-IR, XRD, EDAX and SEM. Their antimicrobial effect was studied by disk diffusion method on two types of bacteria: Pseudomonas aeruginosa and Staphylococcus aureus. RESULTS: FT-IR and XRD tests confirmed the formation of HAp nanoparticles. SEM images showed the morphology and nanostructure of HAp and Ni@HAp. Ni@HAp showed significantly more antimicrobial effects than the other two ions on S. aureus. EDAX confirmed the presence of Ni2+ ions in the Ni@HAp structure and the element map also showed very good dispersion of elements in both HAp and Ni@HAp structures. CONCLUSIONS: HAp nanoparticles doped with nickel ions may be considered as a promising antibacterial treatment in bone tissue engineering and repairing of skeletal injuries contaminated with S. aureus.

Sodium-borohydride exfoliated bismuthene loaded with Mitomycin C for chemo-photo-radiotherapy of triple negative breast cancer.

In current study, a new remotely controlled drug delivery, radio-sensitizing, and photothermal therapy agent based on thioglycolic acid modified bismuth nanosheets is thoroughly evaluated. Bismuth nanosheets were synthesized using sodium borohydride (NaBH4) and Tween 20 through low energy (400 W) sonication within 2 h. The resultant nanosheets were 40-60 nm in size and 1-3 atomic layers in thickness. The morphological and structural characteristics of the nanosheets were studied using transmission electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, Raman spectroscopy and ultraviolet spectroscopy. The surface of the nanosheets was modified using thioglycolic acid, which resulted in enhanced Mitomycin C loading capacity to 274.35% and circumvented the burst drug release due to the improved electrostatic interactions. At pH 7.4 and 5.0, the drug release was significantly boosted from 45.1 to 69.8%, respectively. Thioglycolic acid modified bismuth nanosheets under 1064 nm laser irradiation possessed photothermal conversion efficiency of η=51.4% enabling a temperature rise of 24.9 °C at 100 µg/ml in 5 min. The combination of drug delivery, photothermal therapy, and radio-sensitization greatly damaged the MDA-MB-231 cells through apoptosis and diminished their colony forming.

Thermosensitive TMPO-oxidized lignocellulose/cationic agarose hydrogel loaded with deferasirox nanoparticles for photothermal therapy in melanoma.

Deferasirox (DFX) is an iron-chelating agent effective in treating various kinds of cancers, which inhibits iron metabolism in cancer cells. The recent study aimed to prepare an injectable thermosensitive hydrogel based on lignocellulose and agarose containing deferasirox-loaded polypyrrole nanoparticles for local drug delivery in a combined chemo-photothermal therapy by laser light irradiation. Polypyrrole nanoparticles containing DFX were made by the emulsification method and optimized. Thermosensitive hydrogels were prepared by quaternary ammonium substituted agarose and TMPO-oxidized lignocellulose at different ratios, and the optimal hydrogel was selected based on gelation time, gelation temperature, and injectability. DFX- loaded polypyrrole nanoparticles were then added to the hydrogel, and the drug release, rheology test, injectability, degradation, and swelling percent, as well as cytotoxicity, and photothermal properties, were studied on B16F10, human melanoma cells. The hydrogel with 2 % anionic lignocellulose and 0.5 % cationic agarose showed the shortest gelation time and the highest mechanical strength. It transferred from a liquid state at 4 °C into a semisolid form at 37 °C with a gelation time of 10.3 min. The nanoparticles loaded in hydrogel showed dose-dependent cytotoxicity. The cytotoxic dose of the drug was reduced by laser light irradiation.

PDGF and VEGF-releasing bi-layer wound dressing made of sodium tripolyphosphate crosslinked gelatin-sponge layer and a carrageenan nanofiber layer.

The use of dressings is one of the most common methods for wound treatment. Since most single-layer dressings cannot mimic the hierarchical structure of the skin well, multi-layer dressings have been considered. In this study, a bilayer dressing was fabricated using a gelatin sponge layer cross-linked with sodium tripolyphosphate (Gel-STPP) and a layer of carrageenan nanofibers containing platelet-rich fibrin (Carr-PRF). Chemical interactions between the two layers were characterized by FTIR, and the microstructure was visualized by SEM. It was found that the presence of Carr-PRF nanofiber layer increased tensile strength by 12.96 % (from 0.216 ± 0.015 to 0.268 ± 0.036 MPa) and elastic modulus by 56.70 % (from 0.388 ± 0.072 to 0.608 ± 0.029 MPa) compared to Gel-STPP sponge. Gel-STPP/Carr-PRF wound dressing had a 45.76 ± 4.18 % degradability after 7 days of immersion in phosphate buffered saline (PBS). PRF-containing bilayer wound dressing was able to sustainably release growth factors over 7 days. The Carr-PRF nanofiber layer coated on Gel-STPP sponge was an ideal environment for adhesion and proliferation of L929 cells. Gel-STPP/Carr-PRF bilayer dressing outperformed the other tested samples in terms of angiogenic potential. Average wound closure was 94.21 ± 2.06 % in Gel-STPP/Carr-PRF dressing treated rats after 14 days, and based on the histopathological and immunohistochemical examinations, the Gel-STPP/Carr-PRF dressing group augmented full-thickness wound healing, keratin layer and skin appendages formation after 14 days.

A Systematic Review and Meta-Analysis on the Effect of Flavonoids on Insulin-like Growth Factor and Insulin-like Growth Factor Binding Protein and Incidence of Breast Cancer.

BACKGROUND: Insulin-like growth factor (IGF-1) is associated with breast cancer in menopausal women. Naturally occurring biomolecules found in common dietary protocols, such as flavonoids, play a key role in the inhibition and treatment of cancer. In-vitro/in-vivo studies showed that treatment involving flavonoids led to a reduced risk of breast cancer due to the decrease of IGF-1 level in addition to an increased insulin-like growth factor binding protein (IGFBP)-3. However, clinical studies did not show conclusive results in this regard because they are contradictory. OBJECTIVE: The aim of the present study was to find the effect of flavonoids on IGF-1 and IGFBP-3 and the incidence of breast cancer. METHODS: This systematic review was performed using PubMed, Scopus, ISI Web of Science, and EMBASE databases to collect results about the clinical use of flavonoids and their effects on breast cancer. After eliminating duplicate articles, the title and abstract of the remaining articles were examined in thematic communication, and related clinical articles were selected and studied based on inclusion criteria. The data were extracted from each article, and then statistical analysis was subsequently carried out by Comprehensive Meta-Analysis. RESULTS: The results showed that the effect of flavonoids on changes in IGF1 and IGFBP-3 was not statistically significant. No significant heterogeneity was detected across the studies. Pooled effect size also indicated that the mean change was not statistically significant. No significant heterogeneity was detected across the studies. There was no evidence of publication bias for IGF1 and IGFBP-3. CONCLUSION: This meta-analysis study suggests that flavonoid supplementations have no significant effect on IGF-1 and IGFBP-3, and a high soy diet has beneficial effects on IGF system components, which might be useful in breast cancer.

Assessment of Oxaliplatin-Loaded Iodine Nanoparticles for Chemoradiotherapy of Human Colorectal Cancer (HT-29) Cells.

Colorectal cancer is highly prevalent worldwide and has significant morbidity and mortality in humans. High-atomic-number nanoparticles such as iodine can act as X-rays absorbers to increase the local dose. The synthesis and fabrication of oxaliplatin-loaded iodine nanoparticles, their characterization, cell toxicity, radiosensitivity, cell apoptosis, and cell cycle assay in human colorectal cancer (HT-29) cells are investigated. Results show that the synthesis of a new iodine nanoparticle, polymerized triiodobenzene coated with chitosan and combined with oxaliplatin as a chemotherapeutic drug, performed well in vitro in an intracellular radiosensitizer as chemoradiotherapy agent in HT-29 cell lines. Findings also show that the INPs alone have no impact on cell cycle development and apoptosis. In contrast, oxaliplatin-loaded INPs along with 2 and 6 MV radiation doses produced more apoptosis. The interaction of INPs with mega-voltage photon energies is the cause of a major radiosensitization enhancement in comparison to radiation alone. Furthermore, results show that INPs may work as radiosensitization nanoprobe agents in the treatment of HT-29 cells due to their effect on increasing radiation dose absorption. Overall, iodine nanoparticles may be used in the treatment of colorectal cancers in clinical studies.

Comparison of physical, mechanical and biological effects of leucocyte-PRF and advanced-PRF on polyacrylamide nanofiber wound dressings: In vitro and in vivo evaluations.

Platelet-rich fibrin (PRF) is extracted from the blood without biochemical interference and, also, with the ability of a long-term release of growth factors that can stimulate tissue repair and regerenation. Here, leucocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) were extracted and utilized for the creation of nanofibers containing polyacrylamide (PAAm), PAAm / L-PRF and PAAm / A-PRP through electrospinning processing technique. The effect of the type of PRF on the physical, mechanical and biological properties of the resultant nanofiberous wound dressings are thoroughly evaluated. The results presented in the current study reveals that the fiber diameter is grealtly reduced through the utilization of L-PRF. In addition, mechanical property is also positively affected by L-PRF and the degradation rate is found to be higher compared to A-PRF group. The L929 cells proliferation and adhesion, angiogenesis potential and wound healing ability was significantly higher in PAAm/A-PRF nanofibers compared to pure PAAm and PAAm/L-PRF nanofibers owed to the release of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). Overall, the utilization of L-PRF or A-PRF can improve the physical, mechanical and biological behavior of nanofiber making them an ideal candidate for wound dressings, with the emphasis on the skin tissue repair and regeneration applications.

Cationic Okra gum coated nanoliposomes as a pH-sensitive carrier for co-delivery of hesperetin and oxaliplatin in colorectal cancers.

Oxaliplatin (OXP) is the typical treatment for colorectal cancer. Combining chemotherapeutic drugs can reduce drug resistance and side effects. In the present study, the co-delivery of OXP with Hesperetin (HSP), a natural anti-cancer flavonoid, by nanoliposomes was studied against HT-29 colon cancer cells. Cationic Okra gum (COG) was synthesized to coat nanoliposomes. The successful synthesis of COG was confirmed by NMR spectroscopy. Liposomes were prepared by thin film hydration technique. Formulations containing 0.5, 1, and 2 mg·ml-1 COG, had particle sizes ranging from 145 to 175 nm and zeta potentials for uncoated and coated formulations changed between -29 and -0.403 mV. Coated liposomes released 98 and 66% of HSP and OXP, respectively during 24 h pH-dependently. Cationic Okra gum enhanced the physical stability of the liposomes for about 30 days. The composite liposomes containing OXP and HSP at final concentrations of 1.125 and 125 µM, respectively could generate significant cytotoxicity at 48 h in comparison to each drug alone. Extracted drug-target interactions from the STITCH database, showed that Catalase (CAT) is the common target between OXP and HSP drugs. Measurement of the CAT activity may be used as an indicator to investigate the mechanism of action of these drugs in subsequent experiments.

An overview of the intracellular localization of high-Z nanoradiosensitizers.

Radiation therapy (RT) is a method commonly used for cancer treatment worldwide. Commonly, RT utilizes two routes for combating cancers: 1) high-energy radiation to generate toxic reactive oxygen species (ROS) (through the dissociation of water molecules) for damaging the deoxyribonucleic acid (DNA) inside the nucleus 2) direct degradation of the DNA. However, cancer cells have mechanisms to survive under intense RT, which can considerably decrease its therapeutic efficacy. Excessive radiation energy damages healthy tissues, and hence, low doses are applied for cancer treatment. Additionally, different radiosensitizers were used to sensitize cancer cells towards RT through individual mechanisms. Following this route, nanoparticle-based radiosensitizers (herein called nanoradiosensitizers) have recently gained attention owing to their ability to produce massive electrons which leads to the production of a huge amount of ROS. The success of the nanoradiosensitizer effect is closely correlated to its interaction with cells and its localization within the cells. In other words, tumor treatment is affected from the chain of events which is started from cell-nanoparticle interaction followed by the nanoparticles direction and homing inside the cell. Therefore, passive or active targeting of the nanoradiosensitizers in the subcellular level and the cell-nano interaction would determine the efficacy of the radiation therapy. The importance of the nanoradiosensitizer's targeting is increased while the organelles beyond nucleus are recently recognized as the mediators of the cancer cell death or resistance under RT. In this review, the principals of cell-nanomaterial interactions and which dominate nanoradiosensitizer efficiency in cancer therapy, are thoroughly discussed.