Clay microparticles for the enhancement of bone regeneration: in vitro studies.

Humans develop osteoporosis as they age, a disease characterized by the slow and consistent reduction in bone mass and the subsequent risk of fractures. Due to aging, the mesenchymal stem cells within the bone marrow niche, show a shift in differentiation from osteogenesis to adipogenesis. The challenge of osteoporosis treatment is being met with advances in nanotechnology and tissue engineering. In this study , we evaluated the potential of palygorskite clay mineral microparticles for the promotion of the osteogenic differentiation in human mesenchymal stem cells (hMSCs) in vitro. Alkaline phosphatase (ALP) activity and Alizarin red staining showed that osteogenic differentiation of hMSCs is enhanced in the presence of palygorskite clay. Although, gene expression analysis did not reveal upregulation of several osteogenic markers in the presence of the clay microparticles, another interaction mechanism resulted in the enhanced osteogenic differentiation of hMSCs. The charged surfaces of the palygorskite clay particles interact with the stem cells using their high adhesion characteristics, leading to complete bridging, adherence, and enveloping of the stem cells' cadherins and integrins with their environment. This restoration of the adhesion among the stem cells and their environment most probably promotes/restores the osteogenic differentiation of hMSCs. Therefore, palygorskite clay microparticles are a promising candidate for further in vivo studies on bone regeneration.

Melanoma treatment via non-specific adhesion of cancer cells using charged nano-clays in pre-clinical studies.

The incidence of malignant melanoma has rapidly increased in the last two decades. There are many challenges associated with the current conventional therapies, including tumour size and location, the specificity of treatments, tumour resistance, non-mutually exclusive mutations, drug resistance, and many adverse side effects. Due to conventional therapies having several limitations, we have explored an alternative therapy such as nano-clays; nano-sized natural materials originating from clay fraction of the soil. Recently, clay nanoparticles have increasingly been used as a drug carrier for cancer treatment due to their high absorption, ability to engulf microbes, and low toxicity. In this study, we evaluated the effects of a nano-clays mix on melanoma cell proliferation and cell viability in vitro and melanoma growth in vivo xenograft animal model. The in vitro study revealed that nano-clay treatments significantly reduced melanoma cell proliferation and cell viability in a dosage-dependent manner. The in vivo tumour xenograft model demonstrated that nano-clay mix treatment led to significantly reduced tumour size and weight, decreased tumour cell mitosis, and induced tumour necrosis. These processes owe to the most probable changes in the membrane potential of the cancer cells once nano-clays bind with the former through the high non-specific adhesion characteristic of the cancer cells. As the data suggest an important role of nano-clays as an inhibitor of melanoma cell proliferation and survival, these prove to be a natural and effective medicine for the treatment of melanoma. The proven compatibility of nano-clays with the human cells with little side-effects makes them a highly preferred choice for the treatment of melanoma and probably other types of cancers.

Nano-clays as Potential Pseudo-antibodies for COVID-19.

Despite several efforts, the development of an effective vaccine for COVID-19 may take a much longer time. Traditional/natural medicine, already experienced by humans, could be an earlier solution. Considering the research team's experience in using nano-clays as high-affinity material for cancer metastasis, melanoma treatment, and bone regeneration, we propose to use these nano-clays for the prevention/treatment of COVID-19. Owing to high affinity, nano-clays would capture the viruses before the latter get engaged with human hACE2. In this study, molecular-level simulations and modeling of the interaction of coronavirus spike and hACE2 proteins were performed with and without nano-clays. The results showed a very high level of affinity/cohesiveness among SARS-CoV-2 spike and nano-clays as compared to the one between the former and hACE2. We premise that these nano-clays since already being used as drug carriers could also be injected as "clays-alone" medicine. Recommendations have also been provided for future in vitro and in vivo studies.

Enhancing cancer cell adhesion with clay nanoparticles for countering metastasis.

Cancer metastasis results from the suppression of adhesion between cancer cells and the extracellular matrix, causing their migration from the primary tumor location and the subsequent formation of tumors in distant organs. This study demonstrates the potential use of nano-sized clay mineral particles to modulate adhesions between tumor cells and with the surrounding extracellular matrix. Atomic force microscopy studies of live cell cultures reveal a significant increase in adhesion between tumor cells and their environment after treatment with different types of electrically charged clay nanoparticles. The enhancement of adhesion among cancer cells was further confirmed through scratch type of wound healing assay studies. To provide insight into the adhesion mechanisms introduced by the clay nanoparticles, we performed a molecular-level computer simulation of cell adhesions in the presence and absence of the nanoparticles. Strong van der Waals and electrostatic attractions modelled in the molecular simulations result in an increase in the cohesive energy density of these environments when treated with clay crystallites. The increase in the cohesive energy density after the sorption of clay crystallites on cell-cell and cell-extracellular matrix complexes lends weight to our strategy of using clay nanoparticles for the restoration of adhesion among cancer cells and prevention of metastasis.

Use of nano-sized clay crystallites to restore adhesion among tumor and aging stem cells - a molecular simulations approach.

Adhesion of cells to the ECM is key to the regulation of cellular morphology, migration, proliferation, survival, and differentiation. The decrease in or loss of the cell's ability of mutual adhesiveness has been considered as one of the specific abnormalities in the surface properties of malignant cells. A change in the association of plasma membrane with cytoskeletal structures also seems to have a close relation with these abnormalities. Similar to the role of adhesions in tumor cells, stem cells' self-renewal is also tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. This study has demonstrated through molecular simulations the potential use of smectite (Na-montmorillonite) clay crystallites to create adhesions among tumor and stem cells. High electrostatic energies and cohesive energy densities measured in the simulations after the sorption of clay crystallites on cell-cell and cell-ECM complexes validate the concept of using these crystallites for the purposes. As results of this study are quite promising and clay crystallites could be considered as an option to restore adhesions in tumor and stem cells, other confirmatory tests and live cell culture studies are in process for the final validation.