ORCID Profile
0000-0001-8906-1798
Current Organisation
University of Queensland
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Publisher: University of Queensland Library
Date: 2020
Publisher: American Chemical Society (ACS)
Date: 28-06-2017
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.EJPB.2018.06.017
Abstract: Precise engineering of nanoparticles with systematically varied properties (size, charge surface properties, targeting ligands, etc.) remains a challenge, limiting the effective optimization of nanoparticles for particular applications. Herein we report a single-step microfluidic combinatorial approach for producing a library of single and dual-ligand liposomes with systematically-varied properties including size, zeta potential, targeting ligand, ligand density, and ligand ratio. A targeting ligand folic acid and a cell penetrating peptide TAT were employed to achieve the optimal synergistic targeting effect. In 2D cell monolayer models, the single-ligand folic acid modified liposome didn't show any enhanced cellular uptake, while the incorporation of TAT peptide "switched on" the function of folic acid, and induced significant elevated cellular uptake compared to the single ligand modified liposomes, showing a strong synergistic targeting effect. The folic acid and TAT peptide dual-ligand liposome also demonstrated enhanced tumor penetration as observed using 3D tumor spheroid models. The in vivo study further confirmed the improved tumor targeting and longer tumor retention (up to 72 h) of the dual-ligand liposomes. Our work not only proved the versatility of this microfluidic combinatorial approach in producing libraries of multifunctional liposomes with controlled properties but also revealed the great potential of the optimized liposome formulation for synergistic targeting effects.
Publisher: American Chemical Society (ACS)
Date: 28-02-2018
Abstract: The physicochemical properties of nanoparticles (size, charge, and surface chemistry, etc.) influence their biological functions often in complex and poorly understood ways. This complexity is compounded when the nanostructures involved have variable mechanical properties. Here, we report the synthesis of liquid-filled silica nanocapsules (SNCs, ∼ 150 nm) having a wide range of stiffness (with Young's moduli ranging from 704 kPa to 9.7 GPa). We demonstrate a complex trade-off between nanoparticle stiffness and the efficiencies of both immune evasion and passive/active tumor targeting. Soft SNCs showed 3 times less uptake by macrophages than stiff SNCs, while the uptake of PEGylated SNCs by cancer cells was independent of stiffness. In addition, the functionalization of stiff SNCs with folic acid significantly enhanced their receptor-mediated cellular uptake, whereas little improvement for the soft SNCs was conferred. Further in vivo experiments confirmed these findings and demonstrated the critical role of nanoparticle mechanical properties in regulating their interactions with biological systems.
Publisher: American Chemical Society (ACS)
Date: 29-07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2019
DOI: 10.1101/652099
Abstract: The delivery of adequate concentration of anticancer drugs to tumor site is critical to achieve effective therapeutic treatment, but it is challenging to experimentally observe drug transport and investigate the spatial distribution of the drug in tumor microenvironment. In this study, we investigated the drug transport from a blood vessel to tumor tissue, and explored the effect of tumor size, tumor numbers and positioning on drug concentration distribution using a numerical method in combination with a microfluidic Tumor-Vasculature-on-a-Chip (TVOC) model. The TVOC model is composed of a vessel channel, a tumor channel sandwiched with a porous membrane. A species transport model based on computational fluid dynamics was adapted to investigate drug transport. The numerical simulation was firstly validated using experimental data, and then used to analyse the spatial-temporal structure of the flow, and to investigate the effect of tumor size and positioning on drug transport and drug concentration heterogeneity. We found the drug concentration surrounding the tumor is highly heterogeneous, with the most downstream point the most difficult for drugs to transport and the nearest point to the blood vessel the easiest. Moreover, tumor size and positioning contribute significantly to this drug concentration heterogeneity on tumor surface, which is dramatically augmented in large and downstream-positioned tumors. These studies established the relationship between solid tumor size ositioning and drug concentration heterogeneity in the tumor microenvironment, which could help to understand heterogenous drug distribution in tumor microenvironment.
Publisher: American Chemical Society (ACS)
Date: 04-08-2017
DOI: 10.1021/ACS.LANGMUIR.7B01382
Abstract: Designed peptide surfactants offer a number of advanced properties over conventional petrochemical surfactants, including biocompatibility, sustainability, and tailorability of the chemical and physical properties through peptide design. Their biocompatibility and degradability make them attractive for various applications, particularly for food and pharmaceutical applications. In this work, two new peptide surfactants derived from an hiphilic peptide surfactant (AM1) were designed (AM-S and C
Publisher: American Chemical Society (ACS)
Date: 31-10-2018
Abstract: Nanoparticle tumor accumulation relies on a key mechanism, the enhanced permeability and retention (EPR) effect, but it remains challenging to decipher the exact impact of the EPR effect. Animal models in combination with imaging modalities are useful, but it is impossible to delineate the roles of multiple biological barriers involved in nanoparticle tumor accumulation. Here we report a microfluidic tumor-vasculature-on-a-chip (TVOC) mimicking two key biological barriers, namely, tumor leaky vasculature and 3D tumor tissue with dense extracellular matrix (ECM), to study nanoparticle extravasation through leaky vasculature and the following accumulation in tumor tissues. Intact 3D tumor vasculature was developed with selective permeability of small molecules (20 kDa) but not large ones (70 kDa). The permeability was further tuned by cytokine stimulation, demonstrating the independent control of the leaky tumor vasculature. Combined with tumor spheroids in dense ECM, our TVOC model is capable of predicting nanoparticles' in vivo tumor accumulation, thus providing a powerful platform for nanoparticle evaluation.
Publisher: Wiley
Date: 23-05-2018
Abstract: The concept of dual-ligand targeting has been around for quite some time, but remains controversial due to the intricate interplay between so many different factors such as the choice of dual ligands, their densities, ratios and length matching, etc. Herein, the synthesis of a combinatorial library of single and dual-ligand nanoparticles with systematically varied properties (ligand densities, ligand ratios, and lengths) for tumor targeting is reported. Folic acid (FA) and hyaluronic acid (HA) are used as two model targeting ligands. It is found that the length matching and ligand ratio play critical roles in achieving the synergetic effect of the dual-ligand targeting. When FA is presented on the nanoparticle surface through a 5K polyethylene glycol (PEG) chain, the dual ligand formulations using the HA with either 5K or 10K length do not show any targeting effect, but the right length of HA (7K) with a careful selection of the right ligand ratio do enhance the targeting efficiency and specificity significantly. Further in vitro 3D tumor spheroid models and in vivo xenograft mice models confirm the synergetic targeting efficiency of the optimal dual-ligand formulation (5F2H
Publisher: Wiley
Date: 14-03-2019
Abstract: Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time-consuming, and often fail to replicate human activity. Here a microfluidic tumor-on-a-chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time-elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX-loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.
No related grants have been discovered for Haofei Wang.