Statement of research interests

Low-dimensional polymer-based nanomaterials exhibiting unique physicochemical properties have recently emerged as promising tools for different biomedical applications ranging from tissue engineering to virus interactions. Among this class of materials, two-dimensional nanomaterials have attracted much attention owing to their large surface area and prominent optical, electrical, photothermal, and photodynamic properties along with outstanding loading capacity and fast cellular uptake. Two-dimensional polymers (2D polymers), on the other hand, are single-monomer-thick two-dimensional nanomaterials (2D nanomaterials) with defined and covalently linked repeating units. The physicochemical properties of both 2D nanomaterials and 2D polymers depend strongly on their surface chemistry, which is defined by a combination of parameters including functionality, charge, heteroatom doping, defects, edges and number of layers. All of these factors must be standardized or clearly defined to shed light on the correlation between the molecular structure and properties of 2D polymers and guide further development for biomedical applications.

Hyperbranched polymers, due to high functionality, are strong candidates for multivalent interactions at biointerfaces, exemplified by pathogen blocking with low IC50. They can be transferred to different supramolecular structures by modification of their functional groups or backbone. Versatility of hyperbranched polymers can be developed by copolymerization with different sustainable monomers via circular chemistry. Sustainable synthetic protocols are eco-friendly pathways with minimized environmental concerns that help us and next generations for a safer life with less health risks.

My research interests focus on two-dimensional polymers, polymer-coated two-dimensional nanomaterials, hyperbranched polymers and sustainable chemistry. I am developing new sustainable pathways for the synthesis of functional polymers using waste streams. Moreover, deep understanding of the mechanism of polymerizations and investigation of the relationship between physicochemical properties of functional polymers and their interactions at biointerfaces is among my research interests (Figure 1). I am seeking straightforward polymerizations for the preparation of a broad family of functional polymers at high scale for wide range of biomedical applications.

To achieve these goals, I have focused on three strategies:

 i) Synthesis of polymer-coated two-dimensional nanomaterials with defined functionality: Investigation of their interactions at nano-biointerfaces and their applications for cancer therapy and pathogen interactions

Over the past several years my group has developed a variety of functional nanomaterials based on the ring-opening polymerization of cyclic monomers including, glycidol, ε-caprolactone, lactide and oxazoline (Figure 2 a, e). We have synthesized hyperbranched polyglycerol-b-polyoxazoline copolymers on a 300 g scale and have used them for diabetic wound healing. Results of the clinical phase I study are very promising and we are pushing this project for the next phases. In addition, we have developed a new nondestructive covalent functionalization method for the low-dimensional nanomaterials through which we have been able to prepare new polymer-coated platforms with defined functionalities. Polymer coated two-dimensional nanomaterials have shown great potential in nematode- and pathogen incapacitation as well as healing of infected diabetic wounds (Figure 2 c, d, f-k). The selective and stepwise post-functionalization of nanomaterials together with the nondestructive features of our functionalization opens up new avenues for the construction of photoswitchable nanodevices and functional nanomaterials as candidates for the efficient treatment of multidrug-resistant bacteria and cancer cells as well as the incapacitation of viruses including SARS-CoV-2, HSV, VSV and influenza (Figure 3 a-d).

Figure 1.Our group aims to push forward novel functional polymers for the purpose of minimally invasive therapeutics. We have accumulated experience and expertise in ring opening polymerization, polymer-functionalized nanomaterials, sustainable chemistry, wound healing and pathogen interactions to perform interdisciplinary projects and create a platform for the future applications.

One of our current and future plans is to construct highly functional biocompatible and biodegradable two-dimensional polyols using colloidal platforms. We use covalent and noncovalent methods to construct such polymers. In the covalent method, polyglycerol branches are conjugated to the surface of a platform by pH-cleavable linkers. These branches are then crosslinked side by side to obtain a two-dimensional polyglycerol networks on the surface of the platform. Finally, two-dimensional polyglycerol is separated from the platform by acidification and breaking the pH-cleavable linkers (Figure 4a).

The obtained two-dimensional polyglycerols with a thickness of 3 nm and lateral size of 200 nm are water-soluble polyfunctional nanomaterials and have shown great potential in nanomedicine (Figure 4 b, c). We have used two-dimensional polyglycerols to strongly inhibit herpes simplex virus type 1 (HSV-1) and SARS-CoV-2. The IC₅₀ of the sulfated version of two-dimensional polyglycerol for the inhibition of infection was 3 nM (Figure 4 d-f).

ii) Synthesis of two-dimensional polyols using colloidal platforms: New systems for drug delivery, molecular recognition at biointerfaces, atherosclerosis treatment and diabetic wound healing

 

Figure 3. a) Cryo-TEM image of polyglycerol coated graphene with wrapped influenza A virus, the virions are colored red for better recognition. b) The subvolume of the 3D structure reconstructed from cryo-ET data, shown as “voltex”-presentation (virion orange, polyglycerol coated graphene white) corresponds to the marked area in the upper cryo-electron micrograph, rotated by 45°. It is obvious that the virion is wrapped by polymer-coated sheets. c) Schematic representation of virus wrapping by polymer-coated graphene sheets. d) Surface charge conversion of a polyglycerol-functionalized nanographene sheets after permeation into the tumor tissue. Negatively charged graphene sheets change to positive sheets in tumor, sites and positively charged graphene sheets are quickly taken up by cells (top). Hyperthermia surmounting of multiple drug resistance by functionalized graphene sheets. After, charge-mediated cellular internalization, graphene sheets accumulate into the mitochondria by targeting ligands. Mitochondrial dysfunction and accelerated drug release through hyperthermia results in MDR suppression and efficient chemotherapy.

In noncovalent method, supramolecular interactions between platform and monomers are driving forces for the production of 2D polyols. For example, functionalized cyclodextrins are loaded on the surface of boron nitride by supramolecular interactions and then they are linked side by side to produce a two-dimensional polycylodextrin with a lateral size of several micrometers and thickness of one nanometer (Figure 4 g-i). Our future plan is to use two-dimensional polycylodextrins for pathogen incapacitation.

Figure 4. a) Schematic illustration and synthetic route for two-dimensional hyperbranched polyglycerol (2D-hPG). 2D-hPG can be formed on both sides of graphene; however, for simplification, it is shown only on one side. Vial in the bottom-left shows the aqueous dispersion of graphene sheets with a polyglycerol coverage. Vial in the top-middle displays the aqueous solution after click reaction and acidification. While the graphene template is precipitated in the bottom of vial upon centrifugation, two-dimensional polyglycerol remains in the supernatant. b, c) SFM and TEM images of a 2D-hPG showing monolayers of polyglycerol with 3 nm thickness and around 200 nm lateral size respectively. d) 2D-hPG is sulfated by one pot reaction to obtain extracellular matrix mimic for pathogen interactions. e, f) Schematic representation and IC₅₀ of sulfated version of 2D-hPG for blocking viruses and inhibiting them from infection. g, h, i) Optical microscopy, SFM and SEM images of two-dimensional polycylodextrin.

iii) Sustainable chemistry to produce functional polymers from industrial waste streams

Recently, we have focused on sustainable chemistry and biodegradable materials, which is of great interest, due to the environmental concerns of toxic and non-biodegradable compounds. We combine industrial waste streams from biogenic resources for the synthesis of functional polymers to improve environmental safety.

As an example, we use glycerol and lignin, as byproducts of the biodiesel and paper industries, respectively, to build-up new adsorber materials for the removal of PFAS from water using a circular approach. Lignin is functionalized by alkylamines via Mannich reaction to improve the electrostatic and hydrophobic interactions with PFAS. Glycerol is also changed to linear and hyperbranched polyglycerols by new synthetic protocols, which are used as linkers to crosslink functionalized lignin and making beads. The produced beads are used to remove PFAS from water.

Once the adsorber material is exhausted, we use supercritical carbon dioxide (scCO2) to desorb the PFAS for safe destruction and regenerate the adsorber for repeated use. Because of its long-term biodegradability, the material can eventually be used to improve soil quality at the end of its product life (Figure 5).

Figure 5. We combine two industrial waste streams from biogenic resources (lignin and glycerol) for the synthesis of aminoalkyl-functionalized adsorber beads. In a circular approach these unloaded adsorber beads are used to remove perfluorinated alkyl substances (PFAS) from water. The PFAS loaded beads are recycled with supercritical CO₂ in order to recover the unloaded adsorber beads. At the end of life, the PFAS free adsorber beads have the potential to be used for water and nutrient retention in soil to provide sustainable carbon and nitrogen sources.

Another example is to functionalize lignin by glycerol and use it as a crosslinker to change demolition to green cement with excellent mechanical properties. This is a promising approach to recycle demolition and decrease production of cement, as one of the highest CO₂ emission industries (Figure 6).

Figure 6. In a circular approach lignin-glycerol composite is used as crosslinker to recycle demolition and change it to a new type of cement that can be used in building industry.