Silk nanoparticles were prepared from silk fibroin solutions of domesticated
Bombyx mori and tropical tasar silkworm
Antheraea mylitta and investigated in respect to its particle size, surface ...charge, stability and morphology along with its cellular uptake and release of growth factors. The nanoparticles were stable, spherical, negatively charged, 150–170
nm in average diameter and exhibited mostly Silk II (β-sheet) structure and did not impose any overt toxicity. Cellular uptake studies showed the accumulation of fluorescence isothiocyanate conjugated silk nanoparticles in the cytosol of murine squamous cell carcinoma cells.
In vitro VEGF release from the nanoparticles showed a significantly sustained release over 3 weeks, signifying the potential application as a growth factor delivery system.
Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any ...surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.
Cancer is a leading cause of mortality and morbidity worldwide. Around 90% of deaths are caused by metastasis and just 10% by primary tumor. The advancement of treatment approaches is not at the same ...rhythm of the disease; making cancer a focal target of biomedical research. To enhance the understanding and prompts the therapeutic delivery; concepts of tissue engineering are applied in the development of in vitro models that can bridge between 2D cell culture and animal models, mimicking tissue microenvironment. Tumor spheroid represents highly suitable 3D organoid-like framework elucidating the intra and inter cellular signaling of cancer, like that formed in physiological niche. However, spheroids are of limited value in studying critical biological phenomenon such as tumor-stroma interactions involving extra cellular matrix or immune system. Therefore, a compelling need of tailoring spheroid technologies with physiologically relevant biomaterials or in silico models, is ever emerging. The diagnostic and prognostic role of spheroids rearrangements within biomaterials or microfluidic channel is indicative of patient management; particularly for the decision of targeted therapy. Fragmented information on available in vitro spheroid models and lack of critical analysis on transformation aspects of these strategies; pushes the urge to comprehensively overview the recent technological advancements (e.g. bioprinting, micro-fluidic technologies or use of biomaterials to attain the third dimension) in the shed of translationable cancer research. In present article, relationships between current models and their possible exploitation in clinical success is explored with the highlight of existing challenges in defining therapeutic targets and screening of drug efficacy.
We study electronic phase competition in a strongly correlated system of three coupled spinless Luttinger liquids—one of the simplest models where topologically nontrivial chiral orders may be ...realized. We study the problem as a coupled sine-Gordon model, using a perturbative renormalization group (RG) approach. In contrast with counterparts with fewer fermionic species, here the scaling procedure generates off-diagonal contributions to the phase stiffness matrix, which require both rescaling as well as large rotations of the bosonic fields. These rotations, generally non-abelian in nature, introduce a coupling between different interaction channels even at the tree-level order in the coupling constant scaling equations. We study competing phases in this system, taking into account the aforementioned rotations, and determine its critical behaviour in a variety of interaction parameter regimes where perturbative RG is possible. The phase boundaries are found to be of the Berezinskii–Kosterlitz–Thouless type, and we specify the parameter regimes where symmetry breaking between the three flavours of bosonic fields, orders involving different flavours, and chiral orders may be observed. Our approach and findings may be relevant for understanding phases and transitions at high magnetic fields in semimetals such as bismuth featuring three Fermi pockets.
Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical ...treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease. Combined with high-throughput characteristics, the employment of organ-on-chip technology would allow pharmaceutical companies and clinicians to test new therapeutic compounds and therapies. This will permit the screening of a large battery of new drugs in a fast and economic manner, to accelerate the diagnosis of the disease in the near future, and to test personalized treatments using cells from patients. In this review, we describe the latest advances in the field of organ-on-chip models of cancer metastasis and their integration with advanced imaging, screening and biosensing technologies for future precision medicine applications. We focus on their clinical applicability and market opportunities to drive us forward to the next generation of tumor models for improved cancer patient theranostics.
•Novel materials transmitting in mid-infrared spectral region.•Studied glasses may be good candidates for military and non-linear applications.•Hydrogenic excitonic model is ...applicable.•Transformation of TeO4 structural units into TeO3 units with increase in bismuth content.•B2O3 exists in the both BO3 trigonal and BO4 tetrahedral structural units.
Tellurium oxide based quaternary glasses in the system TeO2⋅B2O3⋅Bi2O3⋅ZnO have been prepared by melt quenching technique. Amorphous nature of the samples has been ascertained by X-ray Diffractogram. The values of density and molar volume increase with increase in Bi2O3 content. Theoretical calculations of crystalline volume (Vc) have also been made. The glass transition temperature (Tg) has been determined using differential scanning calorimetry (DSC) and its value is observed to decrease with increase in Bi2O3 content. IR and Raman spectra of the present glass system indicate that ZnO acts as network modifier and exists in ZnO4 units. TeO2 exists as TeO3, TeO4, and TeO6 structural units and the number of TeO4 groups decreases with increase in bismuth content except for the glass sample with x=5, which shows maximum number of TeO4 structural units among all other studied glass samples and transformation of some of TeO4 structural units into TeO3 structural units is observed with increase in bismuth content. Bismuth plays the role of network modifier with BiO6 octahedral structural units for glass samples with x=5, 10, and 15, whereas, exists in network forming BiO3 pyramidal structural units for glass sample with x=20. B2O3 exists in the form of BO3 trigonal and BO4 tetrahedral structural units. The transmittance of the present glasses is observed to be very high (up to 95%) in the spectral range (λ=2.5–6.5μm) which is of great technological importance. The percentage value of transmittance increases with increase in Bi concentration. The Hydrogenic excitonic model is applicable to the presently studied glasses and the optical band gap energies (Eg) calculated from this model and Tauc’s plots for direct transitions are almost same. Eg decreases with increase in bismuth content, however, the molar refractivity (Rm) show the reverse trend. Metallization criterion for these materials shows that these glasses may be potential candidates for non linear applications.
Osteosarcoma is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. Unfolding of effectual therapeutic strategies against osteosarcoma is impeded ...because of the absence of adequate animal models, which can truly recapitulate disease biology of humans. Tissue engineering provides an opportunity to develop physiologically relevant, reproducible, and tunable in vitro platforms to investigate the interactions of osteosarcoma cells with its microenvironment. Adipose-derived stem cells (ASCs) are detected adjacent to osteosarcoma masses and are considered to have protumor effects. Hence, the present study focuses on investigating the role of reactive ASCs in formation of spheroids of osteosarcoma cells (Saos 2) within a three-dimensional (3D) niche, which is created using gellan gum (GG)–silk fibroin. By modifying the blending ratio of GG–silk, the optimum stiffness of the resultant hydrogels such as GG and GG75: S25 is obtained for cancer spheroid formation. This work indicates that the co-existence of cancer and stem cells can form a spheroid, the hallmark of cancer, only in particular microenvironment stiffness. The incorporation of fibrillar silk fibroin within the hydrophilic network of GG in GG75: S25 spongy-like hydrogels closely mimics the stiffness of commercially established cancer biomaterials (e.g., Matrigel, HyStem). The GG75: S25 hydrogel maintains the metabolically active construct for a longer time with elevated expression of osteopontin, osteocalcin, RUNX 2, and bone sialoprotein genes, the biomarkers of osteosarcoma, compared to GG. The GG75: S25 construct also exhibits intense alkaline phosphatase expression in immunohistochemistry compared to GG, indicating itspotentiality to serve as biomimetic niche to model osteosarcoma. Taken together, the GG–silk fibroin-blended spongy-like hydrogel is envisioned as an alternative low-cost platform for 3D cancer modeling.
Metastatic lung cancer is one of the most lethal forms of cancer and molecular pathways driving metastasis are still not clearly elucidated. Metastatic cancer cells undergo an epithelial-mesenchymal ...transition (EMT) where they lose their epithelial properties and acquire a migratory and invasive phenotype. Here we identify that the expression of microRNAs from the miR-200 family and the miR-183~96~182 cluster are significantly co-repressed in non-small cell lung cancer cell lines and primary tumors from multiple TCGA dataset with high EMT scores. Ectopic expression of the miR-183~96~182 cluster inhibited cancer cell migration and invasion, whereas its expression was tightly modulated by miR-200. We identified Foxf2 as a common, novel and direct target of both these microRNA families. Foxf2 expression tightly correlates with the transcription factor Zeb1 and is elevated in mesenchymal-like metastatic lung cancer cells. Foxf2 expression induced robust EMT, migration, invasion and metastasis in lung cancer cells, whereas Foxf2 inhibition significantly repressed these phenotypes. We also demonstrated that Foxf2 transcriptionally represses E-cadherin and miR-200, independent of Zeb1, to form a double-negative feedback loop. We, therefore, identified a novel mechanism whereby the miR-200 family and the miR-183~96~182 cluster inhibit lung cancer invasion and metastasis by targeting Foxf2.
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