Dual-Purpose 3D-Silica Nanostructure Matrix for Rapid Epigenetic Reprogramming of Tumor Cell to Cancer Stem Cell Spheroid.

Cancer stem cells (CSCs), a rare subpopulation responsible for tumorigenesis and therapeutic resistance, are difficult to characterize and isolate. Conventional method of growing CSCs takes up to 2-8 weeks inhibiting the rate of research. Therefore, rapid reprogramming (RR) of tumor cells into CSCs is crucial to accelerate the stem cell oncology research. The current RR techniques cannot be utilized for CSC RR due to many limitations posed due to isolation requirements resulting in loss of vital data. Hence, a technique that can induce CSC RR without the need for isolation procedures is needed. Here, fabrication of a 3D-silica nanostructured extracellular matrix for RR and in situ monitoring is reported. The RR is tested using three preclinical cancer models. The 3D matrix and a zeta potential study confirm an intense material-cellular interaction resulting in the enhanced expressions of surface and epigenetic biomarkers. Cancer cells require only 3-day period to form CSC spheroids with 3D-silica extracellular matrix. Real-time single-cell monitoring of the methylene blue-induced photodynamic demonstrates the dual functionality. To the authors' knowledge, this is the first study to demonstrate a CSC epigenetic reprogramming using nanostructures. These findings may pave the path for accelerating the stem cell research in oncology.

Reforming DoLS: liberty protection safeguards.

From April 2022, current Deprivation of Liberty Safeguards (DoLS) will be replaced by Liberty Protection Safeguards (LPS). This review article outlines key information about these changes for patients, carers and healthcare professionals, for whom a deprivation of liberty may be relevant.Deprivation of liberty occurs within healthcare settings when someone's freedoms are limited in order to meet their care needs and lack capacity to consent to these arrangements. DoLS, enacted in 2009, ensured that patients deprived of liberties in care settings have similar rights to patients held under the Mental Health Act 1983. However, DoLS have been extensively criticised and considered unfit for purpose, therefore are being replaced by LPS.LPS intend to provide a more robust protection to a wider group of vulnerable people. This includes changes to patient age, transferability between a wider range of care settings, a reduced number of assessments for authorisation and less frequent reauthorisations.

Self-functional gold nanoprobes for intra-nuclear epigenomic monitoring of cancer stem-like cells.

Cancer epigenomic-environment is a core center of a tumor's genetic and epigenetic configuration. Surveying epigenomic-environment of cancer stem-like cells (CSC) is vital for developing novel diagnostic methods and improving current therapies since CSCs are among the most challenging clinical hurdles. To date, there exists no technique which can successfully monitor the epigenomics of CSC. Here, we have developed unique sub-10 nm Self-functional Gold Nanoprobes (GNP) as a CSC epigenomic monitoring platform that can easily maneuver into the nucleus while not producing any conformal changes to the genomic DNA. The GNP was synthesized using physical synthesis method of pulsed laser multiphoton ionization, which enabled the shrinking of GNP to 2.69 nm which helped us achieve two critical parameters for epigenomics monitoring: efficient nuclear uptake (98%) without complex functionalization and no conformational nuclear changes. The GNP efficiently generated SERS for structural, functional, molecular epigenetics, and nuclear proteomics in preclinical models of breast and lung CSCs. To the best of knowledge, this study is first to utilize the intranuclear epigenomic signal to distinguish between CSC from different tissues with >99% accuracy and specificity. Our findings are anticipated to help advance real-time epigenomics surveillance technologies such as nucleus-targeted drug surveillance and epigenomic prognosis and diagnostics.

Evaluation of effect of two different functionalized nanoparticle photodynamic therapy on nanohardness of root dentin-An in vitro study.

INTRODUCTION: The aim of this study was to evaluate the effect of functionalized nanoparticle photodynamic therapy on Nano hardness of root dentin METHODOLOGY: Fifty single rooted lower premolars were decoronated and sectioned into two halves. Then the samples were embedded horizontally in to the acrylic resin to expose the dentin surface. Baseline nanohardness was done at midroot level using a Nanohardness tester. Exposed dentin surfaces were immersed in the following irrigating solutions Post treatment nanohardness testing was done and results were analyzed statistically RESULTS: In general, all the samples in their respective groups had significant change in nanohardness following immersion in irrigant solutions except in NaOCl + EDTA and saline group. CSRB-np and PLGA-MBnp showed increased nanohardness (P = 0.005 and P = 0.007 respectively). Whereas NaOCl + EDTA + CHX showed decrease in nanohardness (P = 0.04). With regards to Modulus of elasticity (MOE), CSRB-np showed significant difference (P = 0.002) compared to the other groups. MOE increased in CSRB-np and PLGA-MBnp while it decreased in all the other groups. CONCLUSION: In this study, the improvement of nanohardness and modulus of elasticity following the immersion of root dentin in CSRB-np solution was demonstrated.

Curcumin Releasing Eggshell Derived Carbonated Apatite Nanocarriers for Combined Anti-Cancer, Anti-Inflammatory and Bone Regenerative Therapy.

Bone cancer or osteosarcoma is an aggressive cancer affecting the long bones and is treated by a combination of surgery and chemotherapy. Local drug delivery directly to the site of bone cancer and the use of plant-based drugs has been explored towards improving the efficacy and decreasing the toxicity of the anti-cancer drugs. Curcumin, derived from turmeric is highly effective against cancer cells and shows very low toxicity against normal cells. Bone repair is facilitated by use of bone substitutes such as bioceramics, amongst which the carbonated apatite (CA) nanocarriers closely mimic the natural bone mineral. In the current work, we have developed CA nanocarriers based local delivery of curcumin as an adjunct treatment for bone cancer. CA nanocarriers with 6 wt.% carbonate were prepared by wet chemical synthesis using synthetic derived (6SWCA) and eggshell derived (6EWCA) precursors along with hydroxyapatite (WHA) as a control. The X-ray diffraction (XRD) patterns showed the CAs to be phase pure with a mean crystallite size of 17 nm. The Fouriertransform infrared spectroscopy (FTIR) analysis of both CAs indicated the carbonate substitution as B-Type. The amount of carbonate substitution was observed to be around 6 wt.% using FTIR and CHNO elemental analyzer. The 6EWCA showed a greater loading (36%) and release (66%) of curcumin than 6SWCA and WHA nanocarriers. The bovine serum albumin (BSA) protein denaturation assay showed the curcumin loaded CAs to be highly anti-inflammatory while their anti-cancer activity was confirmed by the high cytotoxic activity against MG-63 human osteosarcoma cells. Conclusively, an eggshell derived apatite drug delivery system was found to be very suitable to cure osteosarcoma, prevent post-cancer inflammation and modulate bone repair and regeneration.