Nano LIFE

Dexamethasone is a synthetic corticosteroid that has historically been used to treat inflammation, such as from osteoarthritis, spinal cord injury and, more recently, COVID-19. The mechanism of action of dexamethasone is generally known to include attenuation of pro-inflammatory responses as well as upregulation of anti-inflammatory elements. A major issue with the use of dexamethasone is its delivery, as it is normally administered in large quantities via methods like bolus injection to attempt to maintain sufficient concentrations days or weeks after administration. In this review, we examine the mechanism of action of dexamethasone and its effects on three major cell types in the context of specific diseases: macrophages in the context of COVID, chondrocytes in the context of osteoarthritis, and astrocytes in the context of neuro-inflammatory disease. From this, we identify the key proinflammatory cytokines interleukin-1 (IL-1) and Tumor Necrosis Factor alpha (TNF-a) as universal effectors of inflammation that should be targeted alongside dexamethasone administration. Additionally, we review current extended release dosing mechanisms for dexamethasone to act over periods of weeks and months. We suggest that dual treatment of dexamethasone with IL-1 and/or TNF-a monoclonal antibodies will be an effective immediate treatment for inflammation, while the addition of fully developed dexamethasone extended release mechanisms will allow for effective long-term control of inflammatory disease.

The use of antigen delivery systems is essential for inducing antitumor immune responses. Among these, virus-like particles (VLPs) increase the immunogenicity of coupled antigens to stimulate cellular and humoral immune responses. In particular, non-enveloped or capsid VLPs (cVLPs) are a promising antigen delivery system option due to their additional advantages of high production yields and low cost. This review summarizes the latest works on cVLPs in cancer vaccines, supporting cVLPs as a tumor antigen delivery system for immunotherapy and addressing some critical aspects of cVLP use such as production, assembly, decoration and immunization strategies, which can improve the effectiveness of cancer vaccines based on cVLPs.

The current review article explores the binding empathy of carbon nanotubes (CNTs) for different molecular targets, in the context of their potential use to fight against severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). CNTs are touted as one of the most impending theranostic tools, owing to their exceptional mechanical, thermal and optical properties. Furthermore, their structural reliability and functional group flexibility make them especially useful for the design of advanced biosensing devices both for diagnostic and therapeutic applications against SARS-CoV-2. In addition, CNTs could also function both as an antigen carrier and an adjuvant when used concurrently with current and upcoming COVID-19 vaccines.

Objective: In this study, we investigated the antitumor advantages of human mammaglobin (MGB) antibody-modified shikonin (SK)-loaded liposomes (MGB-SK-LPs) in the treatment of breast cancer. Methods: MGB-SK-LPs were prepared via the solvent evaporation method, and their encapsulation rate, drug-loading capacity and in vitro release performance were determined after characterization and analysis. Fluorescein isothiocyanate (FITC) was used as a probe to investigate the cell uptake behavior. The MTT method was used to investigate the cytotoxicity and proliferation behavior, whereas flow cytometry was used to detect the effect of MGB-SK-LPs on tumor cell apoptosis. The antitumor activity of the xenograft tumor model in nude mice was also evaluated. Results: MGB-SK-LPs had a particle size of $208.1\pm 3.7$ nm and a zeta potential of $17.2\pm 4.3$mV. The encapsulation rate of SK and the drug-loading capacity of MGB-liposomes to SK were $89.34\%\pm 0.93\%$ and $25.08\%\pm 0.49\%$, respectively. The MGB-SK-LPs had a sustained-release function with spherical morphology. MGB-SK-LPs, which had low cytotoxicity, can be ingested by breast cancer cells and inhibit proliferation and promote apoptosis. In vivo antitumor activity of SK was significantly enhanced by liposome encapsulation and MGB-targeted modification. Conclusions: MGB-SK-LPs prepared in this study can specifically target breast cancer cells, effectively concentrate drugs on the surface of the tumor cells, and release them slowly. Moreover, they can significantly enhance the antitumor therapeutic effect of SK in vivo, providing a promising solution for targeted treatment of breast cancer.

Engineered three-dimensional (3D) cell culture models can accelerate drug discovery, and lead to new fundamental insights in cell–cell, cell–extracellular matrix (ECM), and cell–biomolecule interactions. Existing hydrogel or scaffold-based approaches for generating 3D tumor models do not possess significant tunability and possess limited scalability for high throughput drug screening. We have developed a new library of hydrogels, called Amikagels, which are derived from the crosslinking of amikacin hydrate (AH) and poly(ethylene glycol) diglycidyl ether (PEGDE). Here we describe the use of Amikagels for generating 3D tumor microenvironments (3DTMs) of breast cancer cells. Biological characteristics of these breast cancer 3DTMs, such as drug resistance and hypoxia were evaluated and compared to those of two-dimensional (2D) monolayer cultures. Estrogen receptor (ER) positive breast cancer 3DTMs formed on Amikagels were more dormant compared to their respective 2D monolayer cultures. Relative to their respective 2D cultures, breast cancer 3DTMs were resistant to cell death induced by mitoxantrone and doxorubicin, which are commonly used chemotherapeutic drugs in cancer, including breast cancer. The drug resistance seen in 3DTMs was correlated with hypoxia seen in these cultures but not in 2D monolayer cultures. Inhibition of Mucin 1 (MUC1), which is overexpressed in response to hypoxia, resulted in nearly complete cell death of 2D monolayer and 3DTMs of breast cancer. Combination of an ER stress inducer and MUC1 inhibition further enhanced cell death in 2D monolayer and 3DTMs. Taken together, this study shows that the Amikagel platform represents a novel technology for the generation of physiologically relevant 3DTMs in vitro and can serve as a platform to discover novel treatments for drug-resistant breast cancer.