Nano Titania Applications in Cancer Theranostics

Titanium is one of the most abundantly utilized nanomaterials for human consumption. Biomedical applications of nano titania include sunscreens, drug delivery, prosthetic implants, bioimaging probes, and antimicrobial and antirheumatic agents for various treatment of diseases, including autoimmune disease, neurogenerative diseases, cardiovascular, musculoskeletal, and cancer. Its applications as a drug delivery vehicle and photosensitizer in cancer therapy and diagnosis are highly appreciated, especially for skin and natural cavities applications. The reactive oxygen species (i.e., H2O2, OH., OH2, 1O2, etc.) generation properties of nano titania after activation with light or ultrasound make it ideal for apoptosis induction in neoplastic cells. In addition, the singlet oxygen (1O2) generating properties make it suitable for bioimaging deep-seated and superficial tumors after activation. Nano titania is highly biocompatible with negligible adverse effects. In this chapter, we will focus on the anticancer effects of nano titania on various types of cancers by employing it as a drug delivery vehicle and sensitizer for external source-activated modalities viz. photodynamic and sonodynamic therapy

Pharmacological activation of mesenchymal stem cells increases gene expression pattern of cell adhesion molecules and fusion with neonatal cardiomyocytes

Cellular therapy is considered a better option for the treatment of degenerative disorders. Different cell types are being used for tissue regeneration. Despite extensive research in this field, several issues remain to be addressed concerning cell transplantation. One of these issues is the survival and homing of administered cells in the injured tissue, which depends on the ability of these cells to adhere. To enhance cell adherence and survival, Rap1 GTPase was activated in mesenchymal stem cells (MSCs) as well as in cardiomyocytes (CMs) by using 8-pCPT-2\u27-O-Me-cAMP, and the effect on gene expression dynamics was determined through quantitative reverse transcriptase-polymerase chain reaction analysis. Pharmacological activation of MSCs and CMs resulted in the upregulation of connexin-43 and cell adhesion genes, which increased the cell adhesion ability of MSCs and CMs, and increased the fusion of MSCs with neonatal CMs. Treating stem cells with a pharmacological agent that activates Rap1a before transplantation can enhance their fusion with CMs and increase cellular regeneration

Lyophilization based isolation of exosomes

Exosomes are nanoscale extracellular vesicles which regulate intercellular communication. They have great potential for application in nanomedicine. However, techniques for their isolation are limited by requirements for advanced instruments and costly reagents. In this study, we developed a lyophilization-based method for isolating exosomes from cultured cells. The isolated exosomes were characterized for protein content using Bradford assay, and for size distribution and shape using scanning electron microscopy (SEM) and nanoparticles tracking analysis (NTA). In addition, CD63, CD9, CD81, HSP70 and TSG101 were evaluated as essential exosomal surface markers using Western blot. Drug loading and release studies were performed to confirm their drug delivery properties using an in vitro model. Exosomes were also loaded with commercial dyes (Cy5, Eosin) for the evaluation of their drug delivery properties. All these characterizations confirmed successful exosome isolation with measurements of less than 150 nm, having a typical shape, and by expressing the known exosome surface protein markers. Finally, tyrosine kinase inhibitors (dasatinib and ponatinib) were loaded on the exosomes to evaluate their anticancer effects on leukemia cells (K562 and engineered Ba/F3-BCR-ABL) using MTT and Annexin-PI assays. The expression of MUC1 protein on the exosomes isolated from MCF-7 cells also indicated that their potential diagnostic properties were intact. In conclusion, we developed a new method for exosome isolation from cultured cells. These exosomes met all the essential requirements in terms of characterization, drug loading and release ability, and inhibition of proliferation and apoptosis induction in Ph+ leukemia cells. Based on these results, we are confident in presenting the lyophilization-based exosome isolation method as an alternative to traditional techniques for exosome isolation from cultured cells

Titania-graphene oxide nanocomposite-based philadelphia-positive leukemia therapy

Philadelphia-positive (Ph+) leukemia is a type of blood cancer also known as acute lymphoblastic leukemia (ALL), affecting 20-30% of adults diagnosed worldwide and having an engraved prognosis as compared to other types of leukemia. The current treatment regimens mainly rely on tyrosine kinase inhibitors (TKIs) and bone marrow transplants. To date, several generations of TKIs have been developed due to associated resistance and frequent relapse, with cardiovascular system anomalies being the most devastating complication. Nanotechnology has the potential to address these limitations by the targeted drug delivery and controlled release of TKIs. This study focused on the titanium dioxide (TiO2) and graphene oxide (GO) nanocomposite employment to load nilotinib and ponatinib TKIs for therapy of Ph+ leukemia cell line (K562) and Ba/F3 cells engineered to express BCR-ABL oncogene. Meanwhile, after treatment, the oncogene expressing fibroblast cells (Rat-1 P185) were evaluated for their colony formation ability under 3D conditions. To validate the nanocomposite formation, the TiO2-GO nanocomposites were characterized by scanning electron microscope, DLS, XRD, FTIR, zeta potential, EDX, and element mapping. The TKI-loaded TiO2-GO was not inferior to the free drugs after evaluating their effects by a cell viability assay (XTT), apoptosis induction, and colony formation inhibition. The cell signaling pathways of the mammalian target of rapamycin (mTOR), signal transducers and activators of transcription 5 (STAT5), and extracellular signal-regulated kinase (Erk1/2) were also investigated by Western blot. These signaling pathways were significantly downregulated in the TKI-loaded TiO2-GO-treated groups. Based on the findings above, we can conclude that TiO2-GO exhibited excellent drug delivery potential that can be used for Ph+ leukemia therapy in the future, subject to further investigations

Hydrophobic iron oxide nanoparticles: Controlled synthesis and phase transfer via flash nanoprecipitation

Iron oxide nanoparticles (IONPs) synthesized via thermal decomposition find diverse applications in biomedicine owing to precise control of their physico-chemical properties. However, use in such applications requires phase transfer from organic solvent to water, which remains a bottleneck. Through the thermal decomposition of iron oleate (FeOl), we systematically investigate the impact of synthesis conditions such as oleic acid (OA) amount, temperature increase rate, dwell time, and solvent on the size, magnetic saturation, and crystallinity of IONPs. Solvent choice significantly influences these properties, manipulating which, synthesis of monodisperse IONPs within a tunable size range (10-30 nm) and magnetic properties (75 to 42 Am2Kg-1) is obtained. To enable phase transfer of IONPs, we employ flash nanoprecipitation (FNP) for the first time as a method for scalable and precise size control, demonstrating its potential over conventional methods. Poly(lactic-co-glycolic acid) (PLGA)-coated IONPs with hydrodynamic diameter (Hd) in the range of 250 nm, high colloidal stability and high IONPs loadings up to 43% were obtained, such physicochemical properties being tuned exclusively by the size and hydrophobicity of starting IONPs. They showed no discernible cytotoxicity in human dermal fibroblasts, highlighting the applicability of FNP as a novel method for the functionalization of hydrophobic IONPs for biomedicine