MXene quantum dots as promising material for immunoengineering

(Nanowerk Spotlight) MXenes are a family of 2D transition metal carbides, nitrides, and carbonitrides that are made by selectively etching MAX phases. Originally discovered in 2011 by two groups of researchers led by Michel W Barsoum and Yury Gogotsi at Drexel University, it wasn’t until 2017 that MXenes' true potential was realized and researchers started intensively researching and discovering new MXenes.
So far, more than 40 MXenes have been reported with various combinations of metal, carbon, and nitrogen atoms, as well as surface functional groups, such as oxygen or halogens. The ultimate number will be far greater and in time they may even develop into the largest family of 2D materials.
MXenes' astonishing properties, such as their metal-like electrical conductivity reaching ∼20 000 S cm-1, render them quite useful in a large number of applications, including energy storage and harvesting, electrodes, optoelectronic, biomedical, communications, and environmental pollution control and water desalination.
Though the basic definition of MXenes as 2D transition metal carbides and nitrides is straightforward, there is enough variety in structures and compositions that defining a terminology for MXenes is necessary when discussing them in detail.
The general formula of MXenes is Mn+1XnTx, where M represents the transition metal site, X represents carbon or nitrogen sites, n can vary from 1 to 4, and Tx (where x is variable) indicates surface terminations on the outer transition metal layers.
The formula is written as (M', M")n+1XnTx if there are two randomly distributed transition metals occupying M sites in the MXene structure (M' and M" representing the two different transition metals).
MXenes are created by etching a MAX phase by mainly using strong etching solutions such as HF, a mixture of fluoride salts and various acids, non-aqueous etchants, halogens, and molten salts etc. This etching process selectively removes the A (Al) atom from layered MAX phases. Through this exfoliation process, the carbide layers are separated into two MXene sheets just a few atoms thick.
In recent years, there has been a rapid growth in MXene research due to their distinctive two-dimensional structure and outstanding properties. Especially, in biomedical applications, MXenes have attracted widespread interest with numerous studies on biosafety, antibacterial, bioimaging, cancer therapy, tissue regeneration, drug delivery system, photothermal therapy and biosensor applications. Although their development is still in the experimental stage, a comprehensive understanding of the current status of MXenes in biomedicine will promote their use in clinical applications.
Recently, Dr. Sanjay Dhingra and his research team at Max Rady College Medicine, University of Manitoba, have reported the synthesis process and biomedical applications of a novel nanomaterial for in vivo treatment of vasculopathy – a general term used to describe any disease affecting blood vessels (Advanced Functional Materials, "Fabrication of Smart Tantalum Carbide MXene Quantum Dots with Intrinsic Immunomodulatory Properties for Treatment of Allograft Vasculopathy").
Step-by-step schematic on the conversation of Ta4AlC3 MAX phase bulk to 0D Ta4C3Tx Mxene quantum dots
Synthesis schematic model, stoichiometry, and materials characterization. Step-by-step schematic on the conversation of Ta4AlC3 MAX phase bulk to 0D Ta4C3Tx MQDs using a facile protocol. Briefly, Ta4AlC3 MAX phase powder was etched using an HCl/NaF etchant to remove Al layers and synthesize Ta4C3Tx MXene nanosheets. This wet etching was performed continuously during the synthesis process for 48 h. Simultaneously, heating at 60 °C enhanced the exfoliation and functionalization of Ta4AlC3 to form accordion-like 2D MXene. The exfoliated Ta4C3Tx nanosheets were further treated by sonication and mechanical vibration to obtain multi-, oligo-, and monolayer flakes, which were subsequently treated using a hydrothermal process to form Ta4C3Tx MQDs with concentrated functional groups as well as stable surface tantalum oxides. (Reprinted from doi:10.1002/adfm.202106786 under a Creative Commons CC BY license)
Through their innovative approach using rational design and synthesis strategies, the researchers developed intrinsically immunomodulatory and anti-inflammatory tantalum carbide MXene quantum dots (Ta4C3Tx MQDs). The team is confident that this new nanomaterial could reduce or even avoid the need for anti-rejection drugs for heart transplant patients.
For patients in the end stages of heart disease, cardiac transplantation is considered to be the gold-standard treatment, providing substantial improvements in survival and quality of life. However, heart transplants are not without risk, and almost all transplant recipients will suffer from mild to potentially fatal forms of complication.
Some of the most common complications are organ rejection, cardiac allograft vasculopathy, graft dysfunction, chronic kidney disease, infection and malignancy. Virtually all heart transplant recipients will suffer at least one complication that could impair their quality of life and potentially even threaten their survival.
For instance, the recipient’s immune system may try to reject the foreign organ. Patients have to take anti-rejection medication, which could result in serious side effects, for the rest of their lives. These immunosuppressant drugs, while suppressing immune responses to keep the body from rejecting the new organ, often cause higher rates of infections in the patient.
The hope for the novel immunoengineered MXene nanomaterials is that these side effects could become a thing of the past.
These MQDs work by altering the surface receptor expression of immune cells and reduce their activation. In other words, MQDs may halt the body's automatic inflammatory response, which is the irreversible first stage of rejection attempts of transplanted organs.
This work comes at a critical juncture in the field, as poor long-term safety of several other MXene compositions is being challenged as viable for eventual clinical translatability.
For example, in vitro studies on cytotoxicity of delaminated Ti3 C2 MXene, the long-term bio inertness of titanium-based materials has since been called into question. In fact, several reports on the cytotoxicity of Ti3C2Tx MXene at medium-to-high concentrations raised significant concern about the eventual clinical translatability of these materials (see for instance: Journal of Hazardous Materials, "In vitro studies on cytotoxicity of delaminated Ti3 C2 MXene ").
In contrast, the new tantalum nanomaterial developed by Dr. Dhingra and his team did not induce oxidative stress and cytotoxicity in cultured human endothelial cells. As they report in their paper, when applied in an in vivo model of organ transplant rejection, intravenous administration of Ta4C3Tx MQDs reduced both immune cell infiltration and structural degeneration within transplanted tissues.
By Yashwant Mahajan, Associate Editor, Nanowerk

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