Chemical and Biomolecular Engineering - Research Publications

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    Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine
    Ju, Y ; Lee, WS ; Pilkington, EH ; Kelly, HG ; Li, S ; Selva, KJ ; Wragg, KM ; Subbarao, K ; Nguyen, THO ; Rowntree, LC ; Allen, LF ; Bond, K ; Williamson, DA ; Truong, NP ; Plebanski, M ; Kedzierska, K ; Mahanty, S ; Chung, AW ; Caruso, F ; Wheatley, AK ; Juno, JA ; Kent, SJ (AMER CHEMICAL SOC, 2022-06-27)
    Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle-immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0-70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68-16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9-377.1) and 2.64-fold (0.76-12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo. PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle-leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA vaccines should be monitored. It may be useful to identify suitable alternatives to PEG for developing next-generation LNP vaccines to overcome PEG immunogenicity in the future.
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    Role of Molecular Interactions in Supramolecular Polypeptide-Polyphenol Networks for Engineering Functional Materials
    Han, Y ; Lafleur, RPM ; Zhou, J ; Xu, W ; Lin, Z ; Richardson, JJ ; Caruso, F (AMER CHEMICAL SOC, 2022-07-01)
    Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid synthesis and study of diverse polypeptide-based materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide-polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (Ka of ∼2 × 104 M-1) and polyproline (Ka of ∼2 × 106 M-1) exhibited stronger interactions with polyphenols than other amino acids (Ka of ∼2 × 103 M-1). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine-tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline-tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.
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    Exploiting Supramolecular Dynamics in Metal–Phenolic Networks to Generate Metal–Oxide and Metal–Carbon Networks
    Pan, S ; Goudeli, E ; Chen, J ; Lin, Z ; Zhong, Q ; Zhang, W ; Yu, H ; Guo, R ; Richardson, JJ ; Caruso, F (Wiley, 2021-06-21)
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    Protein precoating modulates biomolecular coronas and nanocapsule-immune cell interactions in human blood
    Li, S ; Ju, Y ; Zhou, J ; Faria, M ; Ang, C-S ; Mitchell, AJ ; Zhong, Q-Z ; Zheng, T ; Kent, SJ ; Caruso, F (ROYAL SOC CHEMISTRY, 2022-06-09)
    The biomolecular corona that forms on particles upon contact with blood plays a key role in the fate and utility of nanomedicines. Recent studies have shown that precoating nanoparticles with serum proteins can improve the biocompatibility and stealth properties of nanoparticles. However, it is not fully clear how precoating influences biomolecular corona formation and downstream biological responses. Herein, we systematically examine three precoating strategies by coating bovine serum albumin (single protein), fetal bovine serum (FBS, mixed proteins without immunoglobulins), or bovine serum (mixed proteins) on three nanoparticle systems, namely supramolecular template nanoparticles, metal-phenolic network (MPN)-coated template (core-shell) nanoparticles, and MPN nanocapsules (obtained after template removal). The effect of protein precoating on biomolecular corona compositions and particle-immune cell interactions in human blood was characterized. In the absence of a pre-coating, the MPN nanocapsules displayed lower leukocyte association, which correlated to the lower amount (by 2-3 fold) of adsorbed proteins and substantially fewer immunoglobulins (more than 100 times) in the biomolecular corona relative to the template and core-shell nanoparticles. Among the three coating strategies, FBS precoating demonstrated the most significant reduction in leukocyte association (up to 97% of all three nanoparticles). A correlation analysis highlights that immunoglobulins and apolipoproteins may regulate leukocyte recognition. This study demonstrates the impact of different precoating strategies on nanoparticle-immune cell association and the role of immunoglobulins in bio-nano interactions.
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    Sonosynthesis of nanobiotics with antimicrobial and antioxidant properties.
    Zhu, H ; Wen, Q ; Bhangu, SK ; Ashokkumar, M ; Cavalieri, F (Elsevier BV, 2022-05)
    Transforming small-molecule antibiotics into carrier-free nanoantibiotics represents an opportunity for developing new multifunctional therapeutic agents. In this study, we demonstrate that acoustic cavitation produced by high-frequency ultrasound transforms the antibiotic doxycycline into carrier-free nanobiotics. Upon sonication for 1 h at 10-15 W cm-3, doxycycline molecules underwent hydroxylation and dimerization processes to ultimately self-assemble into nanoparticles of ∼100-200 nm in size. Micrometer sized particles can be also obtained by increasing the acoustic power to 20 W cm-3. The nanodrugs exhibited antioxidant properties, along with antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacterial strains. Our results highlight the feasibility of the ultrasound-based approach for engineering drug molecules into a nanosized formulation with controlled and multiple bio-functionalities.
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    Evaluation of a lanthanide nanoparticle-based contrast agent for microcomputed tomography of porous channels in subchondral bone
    Silva, MO ; Kirkwood, N ; Mulvaney, P ; Ellis, A ; Stok, KS (WILEY, 2022-05-19)
    Osteoarthritis (OA) is a chronic joint disease that causes disability and pain. The osteochondral interface is a gradient tissue region that plays a significant role in maintaining joint health. It has been shown that during OA, increased neoangiogenesis creates porous channels at the osteochondral interface allowing the transport of molecules related to OA. Importantly, the connection between these porous channels and the early stages of OA development is still not fully understood. Microcomputed tomography (microCT) offers the ability to image the porous channels at the osteochondral interface, however, a contrast agent is necessary to delineate the different X-ray attenuations of the tissues. In this study BaYbF5 -SiO2 nanoparticles are synthesized and optimized as a microCT contrast agent to obtain an appropriate contrast attenuation for subsequent segmentation of structures of interest, that is, porous channels, and mouse subchondral bone. For this purpose, BaYbF5 nanoparticles were synthesized and coated with a biocompatible silica shell (SiO2 ). The optimized BaYbF5 -SiO2 27 nm nanoparticles exhibited the highest average microCT attenuation among the biocompatible nanoparticles tested. The BaYbF5 -SiO2 27 nm nanoparticles increased the mean X-ray attenuation of structures of interest, for example, porous channel models and mouse subchondral bone. The BaYbF5 -SiO2 contrast attenuation was steady after diffusion into mouse subchondral bone. In this study, we obtained for the first time, the average microCT attenuation of the BaYbF5 -SiO2 nanoparticles into porous channel models and mouse subchondral bone. In conclusion, BaYbF5 -SiO2 nanoparticles are a potential contrast agent for imaging porous channels at the osteochondral interface using microCT.
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    Lysozyme microspheres incorporated with anisotropic gold nanorods for ultrasound activated drug delivery.
    Bhargawa, B ; Sharma, V ; Ganesh, M-R ; Cavalieri, F ; Ashokkumar, M ; Neppolian, B ; Sundaramurthy, A (Elsevier BV, 2022-05)
    We report on the fabrication of lysozyme microspheres (LyMs) incorporated with gold nanorods (NRs) as a distinctive approach for the encapsulation and release of an anticancer drug, 5-Fluorouracil (5-FU). LyMs with an average size of 4.0 ± 1.0 µm were prepared by a sonochemical method and characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). The LyMs were examined using hydrophobic (nile red) as well as hydrophilic (trypan blue) dyes under confocal laser scanning microscopy (CLSM) to obtain information about the preferential distribution of fluorescent molecules. Notably, the fluorescent molecules were accumulated in the inner lining of LyMs as the core was occupied with air. The encapsulation efficiency of 5-FU for LyMs-NR was found to be ∼64%. The drug release from control LyMs as well as LyMs incorporated with NRs was investigated under the influence of ultrasound (US) at 200 kHz. The total release for control LyMs and LyMs incorporated with gold NRs was found to be ∼70 and 95% after 1 h, respectively. The density difference caused by NR incorporation on the shell played a key role in rupturing the LyMs-NR under US irradiation. Furthermore, 5-FU loaded LyMs-NR exhibited excellent anti-cancer activity against the THP-1 cell line (∼90% cell death) when irradiated with US of 200 kHz. The enhanced anti-cancer activity of LyMs-NR was caused by the transfer of released 5-FU molecules from bulk to the interior of the cell via temporary pores formed on the surface of cancer cells, i.e., sonoporation. Thus, LyMs-NR demonstrated here has a high potential for use as carriers in the field of drug delivery, bio-imaging and therapy.
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    Complementary bulk and surface passivations for highly efficient perovskite solar cells by gas quenching
    Tang, S ; Bing, J ; Zheng, J ; Tang, J ; Li, Y ; Mayyas, M ; Cho, Y ; Jones, TW ; Yang, TC-J ; Yuan, L ; Tebyetekerwa, M ; Nguyen, HT ; Nielsen, MP ; Ekins-Daukes, NJ ; Kalantar-Zadeh, K ; Wilson, GJ ; McKenzie, DR ; Huang, S ; Ho-Baillie, AWY (ELSEVIER, 2021-08-18)
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    The Critical Importance of Adopting Whole-of-Life Strategies for Polymers and Plastics
    Moad, G ; Solomon, DH (MDPI AG, 2021-07-23)
    Plastics have been revolutionary in numerous sectors, and many of the positive attributes of modern life can be attributed to their use. However, plastics are often treated only as disposable commodities, which has led to the ever-increasing accumulation of plastic and plastic by-products in the environment as waste, and an unacceptable growth of microplastic and nanoplastic pollution. The catchphrase “plastics are everywhere”, perhaps once seen as extolling the virtues of plastics, is now seen by most as a potential or actual threat. Scientists are confronting this environmental crisis, both by developing recycling methods to deal with the legacy of plastic waste, and by highlighting the need to develop and implement effective whole-of-life strategies in the future use of plastic materials. The importance and topicality of this subject are evidenced by the dramatic increase in the use of terms such as “whole of life”, “life-cycle assessment”, “circular economy” and “sustainable polymers” in the scientific and broader literature. Effective solutions, however, are still to be forthcoming. In this review, we assess the potential for implementing whole-of-life strategies for plastics to achieve our vision of a circular economy. In this context, we consider the ways in which given plastics might be recycled into the same plastic for potential use in the same application, with minimal material loss, the lowest energy cost, and the least potential for polluting the environment.
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    Benthic cyanobacteria: A utility-centred field study.
    Gaget, V ; Almuhtaram, H ; Kibuye, F ; Hobson, P ; Zamyadi, A ; Wert, E ; Brookes, JD (Elsevier BV, 2022-03)
    Although there is growing evidence that benthic cyanobacteria represent a significant source of toxins and taste and odour (T&O) compounds in water bodies globally, water utilities rarely monitor for them. Benthic cyanobacteria grow in an array of matrices such as sediments, biofilms, and floating mats, and they can detach and colonize treatment plants. The occurrence of compounds produced by benthic species across matrix and climate types has not been systematically investigated. Consequently, there is a lack of guidance available to utilities to monitor for and mitigate the risk associated with benthic cyanobacteria. To assess toxin and T&O risk across climatic zones and provide guidance to water utilities for the monitoring of benthic mats, two field surveys were conducted across three continents. The surveys examined the occurrence of six secondary metabolites and associated genes, namely, geosmin, 2-methylisoborneol (MIB), anatoxin-a, saxitoxin, microcystin, and cylindrospermopsin, in benthic environmental samples collected across three climates (i.e., temperate, sub-tropical, and tropical) and a range of matrix types. Existing enzyme-linked immunosorbent assays (ELISAs) and qPCR assays and were used to measure compound concentrations and their associated genes in samples. A novel qPCR assay was designed to differentiate the production of MIB by actinobacteria from that of cyanobacteria. MIB occurrence was higher in warmer climates than temperate climates. Cyanobacteria in benthic mats were the major producers of taste and odour compounds. Floating mats contained significantly higher concentrations of geosmin and saxitoxins compared to other matrix types. Samples collected in warmer areas contained significantly more saxitoxin and cylindrospermopsin than samples collected in temperate climates. While these trends were mainly indicative, they can be used to establish monitoring practices. These surveys demonstrate that benthic mats are significant contributors of secondary metabolites in source water and should be monitored accordingly. Benthic cyanobacteria were the sole producers of T&O in up to 17% of the collected samples compared to actinobacteria, which were sole producers in only 1% of the samples. The surveys also provided a platform of choice for the transfer of methodologies and specific knowledge to participating utilities to assist with the establishment of monitoring practices for benthic cyanobacteria and associated secondary metabolites.