Chemical and Biomedical Engineering - Research Publications

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    Modulating the Selectivity and Stealth Properties of Ellipsoidal Polymersomes through a Multivalent Peptide Ligand Display
    Tjandra, KC ; Forest, CR ; Wong, CK ; Alcantara, S ; Kelly, HG ; Ju, Y ; Stenzel, MH ; McCarroll, JA ; Kavallaris, M ; Caruso, F ; Kent, SJ ; Thordarson, P (Wiley, 2020-05-19)
    There is a need for improved nanomaterials to simultaneously target cancer cells and avoid non‐specific clearance by phagocytes. An ellipsoidal polymersome system is developed with a unique tunable size and shape property. These particles are functionalized with in‐house phage‐display cell‐targeting peptide to target a medulloblastoma cell line in vitro. Particle association with medulloblastoma cells is modulated by tuning the peptide ligand density on the particles. These polymersomes has low levels of association with primary human blood phagocytes. The stealth properties of the polymersomes are further improved by including the peptide targeting moiety, an effect that is likely driven by the peptide protecting the particles from binding blood plasma proteins. Overall, this ellipsoidal polymersome system provides a promising platform to explore tumor cell targeting in vivo.
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    Understanding the Uptake of Nanomedicines at Different Stages of Brain Cancer Using a Modular Nanocarrier Platform and Precision Bispecific Antibodies
    Houston, ZH ; Bunt, J ; Chen, K-S ; Puttick, S ; Howard, CB ; Fletcher, NL ; Fuchs, AV ; Cui, J ; Ju, Y ; Cowin, G ; Song, X ; Boyd, AW ; Mahler, SM ; Richards, LJ ; Caruso, F ; Thurecht, KJ (American Chemical Society (ACS), 2020-05-27)
    Increasing accumulation and retention of nanomedicines within tumor tissue is a significant challenge, particularly in the case of brain tumors where access to the tumor through the vasculature is restricted by the blood–brain barrier (BBB). This makes the application of nanomedicines in neuro-oncology often considered unfeasible, with efficacy limited to regions of significant disease progression and compromised BBB. However, little is understood about how the evolving tumor–brain physiology during disease progression affects the permeability and retention of designer nanomedicines. We report here the development of a modular nanomedicine platform that, when used in conjunction with a unique model of how tumorigenesis affects BBB integrity, allows investigation of how nanomaterial properties affect uptake and retention in brain tissue. By combining different in vivo longitudinal imaging techniques (including positron emission tomography and magnetic resonance imaging), we have evaluated the retention of nanomedicines with predefined physicochemical properties (size and surface functionality) and established a relationship between structure and tissue accumulation as a function of a new parameter that measures BBB leakiness; this offers significant advancements in our ability to relate tumor accumulation of nanomedicines to more physiologically relevant parameters. Our data show that accumulation of nanomedicines in brain tumor tissue is better correlated with the leakiness of the BBB than actual tumor volume. This was evaluated by establishing brain tumors using a spontaneous and endogenously derived glioblastoma model providing a unique opportunity to assess these parameters individually and compare the results across multiple mice. We also quantitatively demonstrate that smaller nanomedicines (20 nm) can indeed cross the BBB and accumulate in tumors at earlier stages of the disease than larger analogues, therefore opening the possibility of developing patient-specific nanoparticle treatment interventions in earlier stages of the disease. Importantly, these results provide a more predictive approach for designing efficacious personalized nanomedicines based on a particular patient’s condition.
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    Engineering of Nebulized Metal-Phenolic Capsules for Controlled Pulmonary Deposition
    Ju, Y ; Cortez-Jugo, C ; Chen, J ; Wang, T-Y ; Mitchell, AJ ; Tsantikos, E ; Bertleff-Zieschang, N ; Lin, Y-W ; Song, J ; Cheng, Y ; Mettu, S ; Rahim, MA ; Pan, S ; Yun, G ; Hibbs, ML ; Yeo, LY ; Hagemeyer, CE ; Caruso, F (John Wiley & Sons, 2020-03-18)
    Particle-based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal–phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from ≈100 to 200 nm in increments of ≈50 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing >85% of the capsules in the lung after 20 h, but <4% remaining after 30 days without causing lung inflammation or toxicity. Single-cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with >90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery.
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    Self-Assembly of a Metal-Phenolic Sorbent for Broad-Spectrum Metal Sequestration
    Rahim, MA ; Lin, G ; Tomanin, PP ; Ju, Y ; Barlow, A ; Bjornmalm, M ; Caruso, F (AMER CHEMICAL SOC, 2020-01-08)
    Metal contamination of water bodies from industrial effluents presents a global threat to the aquatic ecosystem. To address this challenge, metal sequestration via adsorption onto solid media has been explored extensively. However, existing sorbent systems typically involve energy-intensive syntheses and are applicable to a limited range of metals. Herein, a sorbent system derived from physically cross-linked polyphenolic networks using tannic acid and ZrIV ions has been explored for high-affinity, broad-spectrum metal sequestration. The network formation step (gelation) of the sorbent is complete within 3 min and requires no special apparatus. The key to this system design is the formation of a highly stable coordination network with an optimized metal–ligand ratio (1.2:1), affording access to a major fraction of the chelating sites in tannic acid for capturing diverse metal ions. This system is stable over a pH range of 1–9, thermally stable up to ∼200 °C, and exhibits a negative surface charge (at pH 5). The sorbent system effectively sequesters 28 metals in single- and multielement model wastes, with removal efficiencies exceeding 99%. Furthermore, it is demonstrated that this system can be processed as membrane coatings, thin films, or wet gels to capture metal ions and that both the sorbent and captured metal ions can be regenerated or directly used as composite catalysts.
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    Expanding the Toolbox of Metal-Phenolic Networks via Enzyme-Mediated Assembly
    Zhong, Q-Z ; Richardson, JJ ; Li, S ; Zhang, W ; Ju, Y ; Li, J ; Pan, S ; Chen, J ; Caruso, F (Wiley, 2020-01-01)
    Functional coatings are of considerable interest because of their fundamental implications for interfacial assembly and promise for numerous applications. Universally adherent materials have recently emerged as versatile functional coatings; however, such coatings are generally limited to catechol, (ortho‐diphenol)‐containing molecules, as building blocks. Here, we report a facile, biofriendly enzyme‐mediated strategy for assembling a wide range of molecules (e.g., 14 representative molecules in this study) that do not natively have catechol moieties, including small molecules, peptides, and proteins, on various surfaces, while preserving the molecule's inherent function, such as catalysis (≈80 % retention of enzymatic activity for trypsin). Assembly is achieved by in situ conversion of monophenols into catechols via tyrosinase, where films form on surfaces via covalent and coordination cross‐linking. The resulting coatings are robust, functional (e.g., in protective coatings, biological imaging, and enzymatic catalysis), and versatile for diverse secondary surface‐confined reactions (e.g., biomineralization, metal ion chelation, and N‐hydroxysuccinimide conjugation).
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    Modular Assembly of Host-Guest Metal-Phenolic Networks Using Macrocyclic Building Blocks
    Pan, S ; Guo, R ; Bertleff-Zieschang, N ; Li, S ; Besford, QA ; Zhong, Q-Z ; Yun, G ; Zhang, Y ; Cavalieri, F ; Ju, Y ; Goudeli, E ; Richardson, JJ ; Caruso, F (Wiley, 2020-01-02)
    The manipulation of interfacial properties has broad implications for the development of high‐performance coatings. Metal–phenolic networks (MPNs) are an emerging class of responsive, adherent materials. Herein, host–guest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin‐based MPNs are highly permeable (even to high molecular weight polymers: 250–500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (>150°) and superwetting (ca. 0°).