Removal of Uremic Toxin by MXenes
The wearable artificial kidney (WAK) is considered to be a potential candidate offering better quality of life to patients with end-stage renal disease. The key technology, also a major challenge, is the adsorbent system for dialysate regeneration. MXene 2D nanosheets are made of two to four atomic layers of a transition metal interleaved with carbon or nitrogen with surface terminations bonded to the outer metallic layers. The combination of a core transition-metal carbide with surface terminations makes MXenes conductive clay-resembling materials. This suggests that the MXene structure could potentially be fine-tuned to adsorb specific molecules by optimizing the interatomic and interlaminar distance of the material. Additionally, because MXene surfaces are terminated with −OH, −O−, and −F, their affinity with adsorbates could be further enhanced by forming hydrogen bonds on the surface. Therefore, we are devoted to developing a MXene-based adsorbent system to remove uremic toxins from dialysate and even blood directly. As the first step, we have demonstrated that urea, one of the most important uremic toxins, can be rapidly and selectively removed by MXene from aqueous solution and spent dialysate. What’s more, healthy donor hemocompatibility assays showed that MXene Ti3C2Tx has no significant impact on blood clotting, hemolysis, and platelet activation, indicating MXenes are safe to use for blood-contacting applications. In next step, our research work will involve increasing sorption capacity by selecting a different MXene or by surface functionalization, expanding to other uremic toxins (Creatinine, Uric acid, et.al.), and developing a dynamic system approaching to a WAK in clinic.
Sorption of Cytokines and Proteins by Carbon-based Materials
Fast removal of inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), IL-8, and IL-6 from blood circulation is crucial in the medical conditions such as acute organ failure, bacterial and viral infection, sepsis, etc. We have achieved efficient removal of cytokines by employing carbon-based materials, including mesoporous carbide-derived carbon, carbon nanotubes, graphene nanoplatelets (GnP). The pore size (specifically in carbide-derived carbons) and accessible surface area are significant factors governing the rate and effectiveness of the adsorption process. We also extensively work on modification/optimization of surface chemistry of expanded graphite for protein adsorption by using bovine serum albumin (BSA) as a model protein. Based on the adsorptive properties determined in the equilibrium conditions, a flow-through system based on granulated GnP with poly(tetrafluoroethylene) (PTFE) was designed to remove cytokines from blood plasma. This kind of graphitic adsorbent offers open hydrophobic surface fully available for adsorption of proteins and can also be used in treatment of a broad range of conditions ranging from radiation decease and drug overdose to Ebola, Crohn’s decease, Ankylosing Spondylitis and other conditions related to excess of cytokines or toxic proteins in blood. The next step is to modify the materials and develop a system that uses these materials to clean blood, in the same method that the blood would be cleaned in a hospital setting.
Nanodiamonds for Drug Delivery Applications
Nanodiamond powder is one of the most promising carbon nanomaterials for drug delivery applications. Diamond nanoparticles of ~5 nm in size offer a large accessible surface and tailorable surface chemistry; have unique optical, mechanical, and thermal properties, and are non-toxic. Although the potential of nanodiamond in drug delivery has been demonstrated, fundamental mechanisms, thermodynamics, and kinetics of drug adsorption on nanodiamond are still poorly understood. To fully exploit the potential of nanodiamond in drug delivery, attention must be paid to its purity, surface chemistry, dispersion quality, as well as to temperature, ionic composition, and other parameters of the environment that may influence drug adsorption and desorption on nanodiamond. Surface modification of nanodiamond and its effects on adsorption equilibria of several important drugs representative of different classes, including antibiotics, chemotherapeutic, and anti-inflammatory drugs, are currently being explored by our group. With the help of our collaborators both at Drexel and abroad, we are working towards integrating these ND-based drug delivery systems into the body to fight infection and disease.
- F. Meng, M. Seredych, C. Chen, V. Gura, S. Mikhalovsky, S. Sandeman, G. Ingavle, T. Ozulumba, L. Miao, B. Anasori, Y. Gogotsi, MXene Sorbents for Removal of Urea from Dialysate – a Step towards the Wearable Artificial Kidney, ACS Nano, 2018, 12(10), 10518-10528.
- M. Seredych, B. Haines, V. Sokolova, P. Cheung, F. Meng, L. Stone, L. Mikhalovska, S. Mikhalovsky, V. N. Mochalin, Y. Gogotsi, Graphene-Based Materials for the Fast Removal of Cytokines from Blood Plasma, ACS Applied Bio Materials, 2018, 1(2), 436-443.
- S. Yachamanei, G. Yushin, S.H. Yeon, Y. Gogotsi, C. Howell, S. Sandeman, G. Phillips, S. Mikhalovsky, Mesoporous Carbide-derived Carbon for Cytokine Removal from Blood Plasma”, Biomaterials, 2010, 31(18), 4789-4794.
- V. Presser, S.H. Yeon, C. Vakifahmetoglu, C.A. Howell, S.R. Sandeman, P. Colombo, S. Mikhalovsky, Y. Gogotsi. Hierarchical Porous Carbide-Derived Carbons for the Removal of Cytokines from Blood Plasma, Advanced Healthcare Materials, 2012, 1(6), 796-800.
- V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, The Properties and Applications of Nanodiamonds, Nature Nanotechnology, 2011, 7(1), 11.
- A. Pentecost, M. Kim, S. Jeon, Y. Ko, I. C. Kwon, Y. Gogotsi, K. Kim, K. L. Spiller, Immunomodulatory Nanodiamond Aggregate-based Platform for the Treatment of Rheumatoid arthritis, Regenerative Biomaterials, 2019, 6 (3), 163–174.
- V. N. Mochalin, A. Pentecost, X. M. Li, I. Neitzel, M. Nelson, C. Wei, T. He, F. Guo, Y. Gogotsi. Adsorption of Drugs on Nanodiamond: Towards Development of a Drug Delivery Plaform. Molecular Pharmaceutics, 2013, 10(10), 3728-3735.