Particles and molecules: controlled interaction and on-demand release



Our research is focused on the interaction of particles with the surrounding environment that affects practically relevant properties of that environment. The ability of particles to release their drug load when and where necessary affects functioning of the nearby cancer cells or bacteria. Interference of particles with the chemical communication of cells allows for the control of their collective behavior, such as biofilm growth or susceptibility to a viral infection. Similar effects can be achieved by mimicking of cells or viruses with properly functionalized particles.

1. Targeting metastatic colorectal cancer by targeted release drug delivery nanoassemblies We load mesoporous nanoparticles based on silica and hydroxyapatite with an anti-cancer veratridine and seal it inside with casein. Due to their surface charge, the blood-brain-barrier-impermeable particles have selective affinity to cancerous cells. In the tumor tissue, the casein is digested by the MMP-7 protease and acid overexpressed by the cancerous cells, which releases veratridine at the target.

2. Repurposing of tooth desensitizing particles for the on-demand oral drug delivery Tooth hypersensitivity is known to be treated by the occlusion of the dentinal tubules exposed to the oral cavity. We found that a range of nontoxic particles are able to occlude dentinal tubules in an aqueous suspension, can be attached to the engineered surface of dental floss and assist in the pulp cell mineralization and tooth remineralization. We explore ability of these particles to carry antibacterial eugenol or other drugs and release them at the bacteria-affected areas of the tooth known for their elevated acidity by in vitro mimicking the human tooth in a newly developed microfluidic device.

3. Control of the biofilm growth by engineered 2D-carbons We found that functionalized graphite microparticles prepared by mechanoactivated exfoliative Diels-Alder addition to graphite6 inhibit bacterial growth and modify monolayer graphene by p-p stacking. We are exploring the ability of the modified graphite microparticles to carry quorum sensing agents able to control the formation of biofilms on 2D-surfaces.

4. Nontoxic biodegradable carriers for genetic modification of plants Our laboratory has engineered modified nontoxic biodegradable hydroxyapatite nanorods able to carry DNA to the plant cells.8 This nanocarrier is superior to more commonly used carbon nanotubes, which persist in the environment and may cause unintended genetic transfection. We are exploring the potential of our new particles to carry gene editing systems inside the cells and develop commercializable methods for agriculture.

5. Mimicking viral surfaces by nanoparticles to evaluate vaccines and antiviral compounds We study the role of surface molecules in the functioning of the immune system and antiviral drugs, mimicking viruses by similarly sized and shaped fluorescent silica nanoparticles. For instance, covalent attachment of H1N3 antigens to the particles enabled us to rapidly assess concentration of antiviral antibodies and therefore evaluate quality of vaccines. Now we are exploring the role of surface human agglutinins in the suppression of the viral replication.

Undergraduate students will be working under the direct supervision of graduate students and gain experience in the organic synthesis, preparation and characterization of the nanomaterials, and fabrication of microfluidic devices.

Selected Publications

1. Wijewantha, N.W.; Eikanger, M.M.; Antony, R.M.; Potts, R.A., Rezvani, Kh.; Sereda G. Targeting Colon Cancer Cells with Enzyme-Triggered Casein-Gated Release of Cargo from Mesoporous Silica-Based Nanoparticles. Bioconjugate Chemistry, 2021, 32(11), 2353-2365 ; DOI:??

2.Rezvani, K.; Sereda, G. Methods and Compositions for the Treatment of Cancer. US Patent Appl. # 20210093726, April 1, 2021 ; DOI:??

3.Farooq, I.; Moheet, I. A.; Al Shwaimi, E. J. A., In vitro dentin tubule occlusion and remineralization competence of various toothpastes. 2015, 60 (9), 1246-1253; DOI:??

4.Sereda G, Saeedi S. Pre-treatment of dentin with chondroitin sulfate or L-arginine modulates dentin tubule occlusion by toothpaste components. Am J Dent. 2019 Apr;32(2):81-88; DOI:??

5.Sereda G, Rashwan K, Saeedi S, Christianson D, Fraser S, Jordan B. Functionalized silk dental floss as a vehicle for delivery of bioactive minerals and ions to the tooth surface. Am J Dent. 2019, 32(3), 118-123; DOI:??

6. Sereda GA, VanLaecken A, Turner JA. Monitoring Demineralization and Remineralization of Human Dentin by Characterization of its Structure with Resonance-Enhanced AFM-IR Chemical Mapping, Nanoindentation, and SEM. Dent. Mat.. 2019, 35(4), 617-626; DOI:??

7. Subbiah, R.; Balbinot, G.; Collares, F.; Sereda G.; Bertassoni, L. Nanoscale mineralization of cell-laden methacrylated gelatin hydrogels using calcium carbonate - calcium citrate core-shell microparticles. J. Mater. Chem. B, 2021, 9, 9583-9593; DOI:??

8.Fran├ža, C.M.; Tahayeri, A.; Rodrigues, N.S.; Ferdosian, Sh.; Rontani, R.M.P.; Sereda, G.; Ferracane, J.L.; Bertassoni, L.E. The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials. Lab Chip 2020, 20, 405-413; DOI:??

9.Sereda GA, Sarder R, Keppen J. Mechanochemical Organic Functionalization of Graphite Produces Tunable Coatings of Carbon Fibers by Multilayered Graphite Microparticles. Nanomaterial Chem Technol. 2019, 1, 23-31; DOI:??

10.Chilkoor, G.; Sarder, R.; Islam, J.; ArunKumar, K.E.; Ratnayake, I.; Star, Sh.; Jasthi, Bh. K.; Sereda, G.; Koratkar, N.; Meyyappan, M. Maleic anhydride-functionalized graphene nanofillers render epoxy coatings highly resistant to corrosion and microbial attack. Carbon 2020, 159, 586-597; DOI:??

11.Izuegbunam, Ch.; Wijewantha, N.; Wone, B.; Ariyarathne, M.; Sereda G.; Wone, B. W. M. A nano-biomimetic transformation system enables in planta expression of a reporter gene in mature plants and seeds. Nanoscale Adv., 2021, 3, 3240-3250; DOI:??

12.Wone, B.; Sereda, G. Hydroxyapatite Nanocarrier for Genetic Cargo. US Patent Appl. # 17/316,045, May 10, 2021; DOI:??

13.Klonoski JM, Hurtig HR, Juber BA, Schuneman MJ, Bickett TE, Svendsen JM, Burum B, Penfound TA, Sereda G, Dale JB, Chaussee MS, Huber VC. Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus: S. pyogenes super-infection. Vaccine. 2014, 32(40), 5241-5249; DOI:??

14.Huber V, Sereda G, Dale J. Rapid and inexpensive assay for evaluation of antibody efficacy with custom-designed fluorescent nanoparticles. US Patent, Int. Appl., WO 2014145216 A1 20140918. 2014; DOI:??