Hyaluronic Acid-Targeted Niosomes for Effective Breast Cancer Chemostarvation Therapy.

Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC50 values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.

Niosomes containing paclitaxel and gold nanoparticles with different coating agents for efficient chemo/photothermal therapy of breast cancer.

Breast cancer (BC) is one of the most common cancers in women, and chemotherapy is usually used to overcome this cancer. To improve drug delivery to cancer sites and reduce their side effects, nanocarriers such as niosomes (NIOs) are used. Moreover, a combination of other therapeutic methods like photothermal therapy (PTT) can help to enhance the chemotherapy effect. The aim of this research is the design a nanocarrier that simultaneously delivers chemotherapy and PTT agents. To achieve this goal, NIOs containing paclitaxel (PTX) as a chemotherapeutic agent and spherical gold nanoparticles (AuNPs) coated with citrate, chitosan (CS), and polyamidoamine (PAMAM) as a PTT agent were synthesized by thin hydration methods. Their physicochemical properties were determined by dynamic light scattering, UV-Vis, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis. Cellular uptake, cell cytotoxicity, hyperthermia, and apoptosis effects of the proposed system were investigated in the MCF-7 BC cell line. The cellular uptake of NIOs/AuNPs-PAMAM (99.21%) and NIOs/AuNPs-CS (98.93%) by MCF-7 cells was higher than that of NIOs/AuNPs (79.55%), demonstrating that surface charge plays a key role in the cellular uptake of NPs. The MTT assay showed the cell viability of 45.48% for NIOs/AuNPs/PTX, 34.24% for NIOs/AuNPs-CS/PTX, and 37.67% for NIOs/AuNPs-PAMAM/PTX after 48 h of treatment. However, the application of hyperthermia significantly decreased the viability of cells treated with NIOs/AuNPs/PTX (37.72%), NIOs/AuNPs-CS/PTX (10.49%), and NIOs/AuNPs-PAMAM/PTX (4.1%) after 48 h. The apoptosis rate was high in NIOs/AuNPs-PAMAM/PTX (53.24%) and NIOs/AuNPs-CS/PTX (55.4%) confirming the data from MTT. In conclusion, the result revealed that combined PTT with chemotherapy increased cell cytotoxicity effects against the MCF-7 cells, and the AuNPs with various coating agents affected cellular uptake and hyperthermia which can be considered for efficient BC therapy.

Astaxanthin-loaded alginate-chitosan gel beads activate Nrf2 and pro-apoptotic signalling pathways against oxidative stress.

Oxidative stress (OS) plays a crucial role in disease development. Astaxanthin (ATX), a valuable natural compound, may reduce OS and serve as a treatment for diseases like neurodegenerative disorders and cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and OS management. We evaluated ATX's antioxidant activity via Alg-CS/ATX gel beads in vitro. ATX-encapsulated alginate-chitosan (Alg-CS/ATX) gel beads were synthesized and structurally/morphologically characterized by SEM, FT-IR, and XRD. Their biological effects were examined in human umbilical vein endothelial cells (HUVECs) treated with H2O2 through MTT assay, Annexin V/PI, cell cycle studies, and western blotting. Alg-CS effectively carried ATX, with high capacity and reduced pore size. Alg-CS/ATX displayed an 84% encapsulation efficiency, maintaining stability for 30 days. In vitro studies showed a 1.4-fold faster release at pH 5.4 than at neutral pH, improving ATX's therapeutic potential. HUVECs treated with Alg-CS/ATX showed enhanced viability via increased Nrf2 expression. Alg-CS gel beads exhibit significant potential as a biocompatible vehicle for delivering ATX to combat OS with considerable opportunity for clinical applications.

A review of the therapeutic potential of dental stem cells as scaffold-free models for tissue engineering application.

In the realm of regenerative medicine, tissue engineering has introduced innovative approaches to facilitate tissue regeneration. Specifically, in pulp tissue engineering, both scaffold-based and scaffold-free techniques have been applied. Relevant articles were meticulously chosen from PubMed, Scopus, and Google Scholar databases through a comprehensive search spanning from October 2022 to December 2022. Despite the inherent limitations of scaffolding, including inadequate mechanical strength for hard tissues, insufficient vents for vessel penetration, immunogenicity, and suboptimal reproducibility-especially with natural polymeric scaffolds-scaffold-free tissue engineering has garnered significant attention. This methodology employs three-dimensional (3D) cell aggregates such as spheroids and cell sheets with extracellular matrix, facilitating precise regeneration of target tissues. The choice of technique aside, stem cells play a pivotal role in tissue engineering, with dental stem cells emerging as particularly promising resources. Their pluripotent nature, non-invasive extraction process, and unique properties render them highly suitable for scaffold-free tissue engineering. This study delves into the latest advancements in leveraging dental stem cells and scaffold-free techniques for the regeneration of various tissues. This paper offers a comprehensive summary of recent developments in the utilization of dental stem cells and scaffold-free methods for tissue generation. It explores the potential of these approaches to advance tissue engineering and their effectiveness in therapies aimed at tissue regeneration.

Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin.

AIMS AND OBJECTIVE: The aim of this study was the preparation of mesoporous silica nanoparticles co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation of HN5 cells exposed to Rut-Cur-MSNs was evaluated. Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals; however, their low aqueous solubility and poor bioavailability limited their applications. The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the objective of this study. METHODS: The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut-Cur-MSNs was assessed compared to control untreated cells. RESULTS: The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05). CONCLUSION: The achieved results recommend that the prepared mesoporous silica nanoparticles containing rutin and curcumin can be a useful nanoformulation for the treatment of cancer. The produced nanomaterial in this study can be helpful for cancer therapy.

Effect of curcumin-containing nanofibrous gelatin-hydroxyapatite scaffold on proliferation and early osteogenic differentiation of dental pulp stem cells.

BACKGROUND: In recent years, the electrospinning method has received attention because of its usage in producing a mimetic nanocomposite scaffold for tissue regeneration. Hydroxyapatite and gelatin are suitable materials for producing scaffolds, and curcumin has the osteogenesis induction effect. AIMS: This study aimed to evaluate the toxicity and early osteogenic differentiation stimulation of nanofibrous gelatin-hydroxyapatite scaffold containing curcumin on dental pulp stem cells (DPSCs). OBJECTIVE: The objective of the present investigation was the evaluation of the proliferative effect and primary osteogenic stimulation of DPSCs with a nanofibrous gelatin-hydroxyapatite scaffold containing curcumin. Hydroxyapatite and gelatin were used as suitable and biocompatible materials to make a scaffold suitable for stimulating osteogenesis. Curcumin was added to the scaffold as an osteogenic differentiation-enhancing agent. METHODS: The effect of nano-scaffold on the proliferation of DPSCs was evaluated. The activity of alkaline phosphatase (ALP) as the early osteogenic marker was considered to assess primary osteogenesis stimulation in DPSCs. RESULTS: The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control after 14 days (P<0.05). CONCLUSION: The produced nanofibrous gelatin-hydroxyapatite scaffold containing curcumin can be utilized as a potential candidate in tissue engineering and regeneration of bone and tooth. FUTURE PROSPECTS: The prepared scaffold in the present study could be a beneficial biomaterial for tissue engineering and the regeneration of bone and tooth soon.

Co-Delivery of Cisplatin and Curcumin Using Mesoporous Silica Nanoparticles to Improve their Anticancer Effects.

AIMS: This study aimed to prepare and evaluate the physicochemical and anticancer properties of cisplatin and curcumin-loaded mesoporous silica nanoparticles (Cis-Cur-MSNs). BACKGROUND: In recent years, combination treatment has attained better outcomes than monotherapy in oncology. Cis-Cur-MSNs were prepared by precipitation technique. OBJECTIVE: The objective of the present study was the evaluation of the physicochemical and anticancer properties of cisplatin and curcumin-loaded mesoporous silica nanoparticles (Cis-Cur-MSNs). METHODS: The prepared materials were assessed in terms of physicochemical methods. The drug release pattern from the MSNs was also evaluated via ultraviolet spectrophotometry. In addition, the porosity and surface area of prepared nanoparticles were determined using the Brunauer-Emmett-Teller (BET) technique. The cytotoxicity of Cis-Cur-MSNs was evaluated on the HN5 cells as head and neck squamous carcinoma cell lines. Furthermore, ROS production of Cis-Cur-MSNs treated cells was evaluated compared with untreated cells. RESULTS: According to the results, prepared nanoparticles displayed nanometer size, rod morphology, and negative surface charge with mesoporous structure belonging to the MCM-41 family (twodimensional hexagonal). Regarding the results of BET adsorption and desorption isotherm analysis for Cis-Cur-MSNs and drug-free MSNs, pore diameter, pore volume, specific surface area, and drug-loaded pore area in MSNs were decreased. In the first 10 days, the prepared nanoparticles exhibited a relatively rapid release pattern for cisplatin and curcumin, and until the 35th day, the release of them from the MSNs continued slowly. CONCLUSION: The cytotoxic effect of Cis-Cur-MSNs was significantly more than Cur-MSNs and Cis- MSNs in 24 and 48 h incubation time (p < 0.05). The results suggest that Cis-Cur-MSNs may be beneficial in the development of a cancer treatment protocol. Others: The prepared nanoparticle in the present study could be a potential biomaterial for cancer treatment.

Effect of Curcumin on the Head and Neck Squamous Cell Carcinoma Cell Line HN5.

BACKGROUND: Curcumin has been isolated from the rhizomes of Curcuma longa. Over the years, it has shown outstanding therapeutic potential in various human disorders, including cancers. OBJECTIVE: The aim is to study curcumin's effects on the apoptosis signaling pathway in the head and neck squamous cell carcinoma (HNSCC) cell line HN5. METHODS: The cytotoxicity of curcumin on HN5 cells were assessed. In addition, HN5 cells were also treated with curcumin to evaluate its effect on the caspase-8, -9, Bcl-2, Bax, and Stat3 gene expressions. RESULTS: The results exhibited that cell viability reduced following curcumin treatment in a concentration- dependent manner. Curcumin treatment caused decreased expression of Bcl2, with simultaneous upregulation of the Bax/Bcl2 ratio. Curcumin increased caspase-9 expression, did not affect caspase-8, and decreased Stat3 expression. The induction of the mitochondria-dependent apoptosis pathway of curcumin happened by modulating the expression of Bcl2 and Bax genes, resulting in the caspase-9 activation. Furthermore, curcumin decreased the expression of the Stat3 in HN-5 cells. CONCLUSIONS: In conclusion, curcumin showed marked anticancer effects in the HN-5 cell line by modulating Stat-3; Bax/Bcl-2 expression in vitro.

Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.

Chitosan (CS)-based pH-sensitive nanocomposites were fabricated for the targeted delivery of doxorubicin (DOX) to osteosarcoma cells. To prepare the nanocomposite, CS was functionalized with succinic anhydride (SA) (CS-SA). CS-folic acid (FA) conjugates were produced by the conjugation of CS with FA via an amide bond. Next, Fe3O4 magnetic nanoparticles (MNPs) ferrofluid was fabricated, and nanocomposite was produced using MNPs and synthesized CS-SA/CS-FA and CS-SA via an inclusion formation between -COOH groups of CS-SA and hydroxyl groups of Fe3O4. Finally, DOX molecules were loaded onto the nanocomposites. The nanocomposites were characterized through FT-IR, DLS, XRD, VSM, TEM, and UV-Vis spectroscopy analyses. DOX release profile at various pHs indicated an enhanced release of DOX in acidic conditions. The cytotoxicity assay demonstrated that the nanocarriers alone were cytocompatible on cells examined. The MG-63 cells, which partly express the folate receptors (FRs), particularly FR-α, showed meaningfully higher cellular uptake of the DOX-loaded CS-FA/CS-SA@MNPs than the FR-negative lung cancer A549 cells. The DOX-loaded CS-FA/CS-SA-MNPs could induce significant cytotoxicity in the MG-63 cells but not in A549 cells. Based on these findings, the DOX-loaded CS-FA/ CS-SA-MNPs might be considered a smart pH-sensitive nanosystem for the targeted delivery of anticancer agents to osteosarcoma cancer cells.

Application of Collagen and Mesenchymal Stem Cells in Regenerative Dentistry.

Collagen is an important macromolecule of Extracellular Matrix (ECM) in bones, teeth, and temporomandibular joints. Mesenchymal Stem Cells (MSCs) interact with the components of the ECM such as collagen, proteoglycans, Glycosaminoglycans (GAGs), and several proteins on behalf of variable matrix elasticity and bioactive cues. Synthetic collagen-based biomaterials could be effective scaffolds for regenerative dentistry applications due to mimicking of host tissues' ECM. These biomaterials are biocompatible, biodegradable, readily available, and non-toxic to cells whose capability promotes cellular response and wound healing in the craniofacial region. Collagen could incorporate other biomolecules to induce mineralization in calcified tissues like bone and tooth. Moreover, the addition of these molecules or other polymers to collagen-based biomaterials could enhance mechanical properties, which is important in load-bearing areas such as the mandible. A literature review was performed via a reliable internet database (mainly PubMed) based on MeSH keywords. This review first describes the properties of collagen as a key protein in the structure of hard tissues. Then, it introduces different types of collagens, the correlation between collagen and MSCs, and the methods used to modify collagen in regenerative dentistry, including recent progression on the regeneration of periodontium, dentin-pulp complex, and temporomandibular joint by applying collagen. The prospects and challenges of collagen-based biomaterials in the craniofacial region are pointd out.

MUC-1 aptamer conjugated InP/ZnS quantum dots/nanohydrogel fluorescent composite for mitochondria-mediated apoptosis in MCF-7 cells.

The combined use of nanohydrogels (NHGs) and quantum dots (QDs) has resulted in the development of a nanoscaled drug delivery system (DDS) with fluorescence imaging potential. NHG-QDs composite loaded with anti-cancer drugs could be applied as an effective theranostics for simultaneous diagnosis and therapy of cancer cells. Here, we report on the synthesis of NHG-QDs nanosystem (NS) conjugated with an amino-modified MUC-1 aptamer (Ap) and loaded with hydrophobic paclitaxel (PTX). To effectively target and eradicate breast cancer MCF-7 cells, the nanocomposite was further loaded with the inhibitor of lactate dehydrogenase (LDH), sodium oxamate (SO) (Ap-NHG-QDs-PTX-SO) to inhibit the conversion of pyruvate to lactate via LDH and disrupting glycolysis. Results obtained from in vitro analysis (MTT assay, apoptosis/necrosis assessment, evaluation of mitochondria targeting, and gene expression profiling) revealed that Ap-NHG-QDs-PTX-SO NS could significantly target and inhibit MCF-7 cells and also induce mitochondria-mediated apoptosis. Collectively, the Ap-NHG-QDs-PTX-SO NS is proposed to serve as a robust theranostics for simultaneous imaging and therapy of breast cancer and other types of solid tumors.

Phytochemicals impact on osteogenic differentiation of mesenchymal stem cells.

Medicinal plants have always been utilized for the prevention and treatment of the spread of different diseases all around the world. To name some traditional medicine that has been used over centuries, we can refer to phytochemicals such as naringin, icariin, genistein, and resveratrol gained from plants. Osteogenic differentiation and mineralization of stem cells can be the result of specific bioactive compounds from plants. One of the most appealing choices for therapy can be mesenchymal stem cells (MSCs) because it has a great capability of self-renewal and differentiation into three descendants, namely, endoderm, mesoderm, and ectoderm. Stem cell gives us the glad tidings of great advances in tissue regeneration and transplantation field for treatment of diseases. Using plant bioactive phytochemicals also holds tremendous promises in treating diseases such as osteoporosis. The purpose of the present review article thus is to investigate what are the roles and consequences of phytochemicals on osteogenic differentiation of MSCs.

Smart stimuli-responsive biopolymeric nanomedicines for targeted therapy of solid tumors.

Solid tumors form a permissive microenvironment with irregular features, including high pressured tumor interstitial fluid with acidic pH, co-adaptation of cancer cells with other cells like the immune system cells, abnormal metabolism and anomalous overexpression of various pieces of molecular machinery. The functional expressions of several oncomarkers in different solid tumors have led to the development of targeted drug-delivery systems (DDSs). As a new class of DDSs, stimuli-responsive nanomedicines (SRNMs) have been developed using advanced nanobiomaterials such as biopolymers that show excellent biocompatibility with low inherent immunogenicity. In this review, we aim to overview different types of SRNMs, present deep insights into the stimuli-responsive biopolymers and discuss the most up-to-date progress in the design and development of SRNMs used as advanced DDSs for targeted therapy of cancer.

The effect of electromagnetic fields on survival and proliferation rate of dental pulp stem cells.

Aims: Extremely low-frequency electromagnetic fields (ELF-EMF) can affect biological systems and alter some cell functions like proliferation rate. Dental pulp tissue is known as a source of multipotent stromal stem cells (MSCs), which can be obtained by a less invasive and more available process compared to bone marrow-derived stem cells (BMSCs). This study aimed to consider the effect of ELF-EMF on proliferation rates of human dental pulp stem cells (hDPSCs).Material and methods: ELF-EMF was generated by a system including autotransformer, multi-meter, solenoid coils, teslameter and its probe. The effect of ELF-EMF with the intensity of 0.5 and 1 mT and 50 Hz on the proliferation rate of hDPSCs was assessed in 20 and 40 min per day for 7 days. MTT assay and DAPI test were used to determine the growth and proliferation of DPSCs.Results: Based on MTT, ELF-EMF has maximum effect with the intensity of 1 mT for 20 min/day on the proliferation of hDPSCs. The survival and proliferation rate in all exposure groups were significantly higher than the control group. Based on the data obtained from MTT and DAPI assay, the number of viable cells in the group exposed to 1 mT for 20 min/day was higher than other groups (p < .05).Conclusions: Regarding to the results of this study, 0.5 and 1 mT ELF-EMF can enhance survival and proliferation rates of hDPSCs.

Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids.

AIMS: The extracellular matrix (ECM) within the tumor nest plays a key role in cancer cell proliferation and invasion. It has been proven that the increased density of ECM, especially collagen network, correlates with the poor distribution of gold-nanoparticles (GNPs) to the tumor mass. Here, for the first time, we examined the combined effect of collagenase (COL) with metformin (MET)-conjugated GNPs on mammosphere generated from JIMT-1 breast cell line in vitro. MAIN METHODS: Mammospheres (on days 7 and 14) and monolayer culture were treated with MET, MET-GNPs, and a mixture of COL-GNPs and MET-GNPs for 5 days. To assess the impacts of the engineered nanoparticles (NPs) on the survival/apoptosis of cancer cells and cancer stem cells (CSCs), the amount/activity of collagen and the expression of pyruvate kinase M2, different methods were applied, including MTT, flow cytometry, immunofluorescence, ELISA and real-time PCR analyses. Our results confirmed the enhanced cytotoxic effects of MET-GNPs combined with COL-GNPs on mammospheres compared to the cells treated with MET alone or MET-GNPs. KEY FINDINGS: Upon treatment with the mixture of MET-GNPs and COL-GNPs, the population of the apoptotic cells was significantly increased. A marked reduction was found in the number of CD24-/CD44+ CSCs and the amount of collagen in the group received a mixture of MET-GNPs and COL-GNPs. SIGNIFICANCE: Based on our findings, the use of COL can improve the cellular interaction/penetration of MET-GNPs in mammospheres and its antitumor impacts on the CSCs.