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107. Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: The importance of reproducing blood-brain barrier heterogeneity

Author

Brighi, Caterina, Reid, Lee, Genovesi, Laura A., Kojic, Marija, Millar, Amanda, Bruce, Zara, White, Alison L., Day, Bryan W., Rose, Stephen, Whittaker, Andrew K., Puttick, Simon, Brighi, Caterina, Reid, Lee, Genovesi, Laura A., Kojic, Marija, Millar, Amanda, Bruce, Zara, White, Alison L., Day, Bryan W., Rose, Stephen, Whittaker, Andrew K., and Puttick, Simon

Abstract

The clinical translation of new nanoparticle-based therapies for high-grade glioma (HGG) remains extremely poor. This has partly been due to the lack of suitable preclinical mouse models capable of replicating the complex characteristics of recurrent HGG (rHGG), namely the heterogeneous structural and functional characteristics of the blood-brain barrier (BBB). The goal of this study is to compare the characteristics of the tumor BBB of rHGG with two different mouse models of HGG, the ubiquitously used U87 cell line xenograft model and a patient-derived cell line WK1 xenograft model, in order to assess their suitability for nanomedicine research. Method: Structural MRI was used to assess the extent of BBB opening in mouse models with a fully developed tumor, and dynamic contrast enhanced MRI was used to obtain values of BBB permeability in contrast enhancing tumor. H&E and immunofluorescence staining were used to validate results obtained from the in vivo imaging studies. Results: The extent of BBB disruption and permeability in the contrast enhancing tumor was significantly higher in the U87 model than in rHGG. These values in the WK1 model are similar to those of rHGG. The U87 model is not infiltrative, has an entirely abnormal and leaky vasculature and it is not of glial origin. The WK1 model infiltrates into the non-neoplastic brain parenchyma, it has both regions with intact BBB and regions with leaky BBB and remains of glial origin. Conclusion: The WK1 mouse model more accurately reproduces the extent of BBB disruption, the level of BBB permeability and the histopathological characteristics found in rHGG patients than the U87 mouse model, and is therefore a more clinically relevant model for preclinical evaluations of emerging nanoparticle-based therapies for HGG.

Published
2020

108. Sodium-Ion Storage Mechanism in Triquinoxalinylene and a Strategy for Improving Electrode Stability

Author

Zhao, Qinglan, Zhao, Wei, Zhang, Cheng, Wu, Yilan, Yuan, Qinghong, Whittaker, Andrew K., Zhao, X.S., Zhao, Qinglan, Zhao, Wei, Zhang, Cheng, Wu, Yilan, Yuan, Qinghong, Whittaker, Andrew K., and Zhao, X.S.

Abstract

Sodium-ion batteries are a promising alternative to lithium-ion batteries. In particular, organic sodium-ion batteries employing environmentally friendly organic materials as electrodes are gaining increasing research interest for developing secondary batteries as a result of the ease of processing, low cost, and flexibility of the organic electrode materials. Triquinoxalinylene (TQA) is a very promising organic electrode material for sodium-ion batteries. However, the poor cycling stability of TQA is impeding its adoption as an electrode material. In this work, we investigated the sodium-ion storage mechanism in TQA and the decay in capacity using both experimental and computational means. A strategy for improving the cycling stability is proposed, and it is demonstrated that the retention of capacity can be significantly improved from 31 to 85%. © Published 2020 by the American Chemical Society.

Published
2020

109. Ultrasensitive Magnetic Tuning of Optical Properties of Films of Cholesteric Cellulose Nanocrystals

Author

Chen, Tianxing, Zhao, Qinglan, Meng, Xin, Li, Yao, Peng, Hui, Whittaker, Andrew K., Zhu, Shenmin, Chen, Tianxing, Zhao, Qinglan, Meng, Xin, Li, Yao, Peng, Hui, Whittaker, Andrew K., and Zhu, Shenmin

Abstract

Chiral photonic crystals derived from the self-assembly of cellulose nanocrystals (CNCs) have found important applications in optical devices due to the capacity to adjust the chiral nematic phase under external stimulus, in particular an applied magnetic field. To date, strong magnetic fields have been required to induce an optical response in CNC films. In this work, the self-assembly of films of CNCs can be tuned by applying an ultrasmall magnetic field. The CNCs, decorated with Fe3O4 nanoparticles (Fe3O4/CNCs), were dispersed in suspensions of neat CNCs so as to alter the magnetic response of the CNCs. A subsequent process of dispersion not only prevents the clumping of the magnetic nanoparticles but also enhances the sensitivity to an applied magnetic field. A small magnetic field of 7 mT can tune the self-assembly and the microstructure of the CNCs. The pitch of the chiral structure decreased with an increase in applied magnetic field, from 302 to 206 nm, for fields from 7 to 15 mT. This phenomenon is opposite that observed for neat CNCs, in which the pitch is observed to increase with an increase in the external magnetic strength. The optical response under application of an ultrasmall magnetic field could help with theoretical research and enable more applications, such as sensors or nanotemplating agents. Copyright © 2020 American Chemical Society.

Published
2020

124. Microconfinement from Dendronized Chitosan Oligosaccharides for Mild Synthesis of Silver Nanoparticles.

Author

Yi Yao, Shijie Cao, Xiacong Zhang, Jiatao Yan, Wen Li, Whittaker, Andrew K., and Afang Zhang

Abstract

Synthesis of noble metal nanoparticles with controllable sizes and morphologies by environment-friendly methods is scientifically important and technologically challenging. Here, we report fabrication of monodispersed silver nanoparticles (AgNPs) in aqueous conditions with dendronized chitosan oligosaccharides (CSOs) as templates. These dendronized CSOs carry three-folded dendritic oligoethylene glycol pendants, which integrate the features of biocompatibility from oligosaccharides, as well as multi-valency and crowding structure effects from dendronized topologies. The crowded dendrons afford a hydrophobic microenvironment for these polymers to complex with silver ions and mediate their conversion to form narrowly distributed AgNPs when triggered with low energy visible light. AgNPs embedded within dendronized CSOs formed stable nanocomposites, which exhibit excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria. Characteristic encapsulation and shielding effects, together with their excellent biocompatibility, make these CSOs appealing for eco-friendly and controllable fabrication of precious metal nanoparticles, which are expected to find various bio-applications. [ABSTRACT FROM AUTHOR]

Published
2022
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125. Sustained release ketamine-loaded porous silicon-PLGA microparticles prepared by an optimized supercritical CO2 process.

Author

Xu, Weizhi, Zhao, Zonglan, Falconer, James, Whittaker, Andrew K., Popat, Amirali, Smith, Maree T., Kumeria, Tushar, and Han, Felicity Y.

Abstract

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO2) method, thereby avoiding the use of organic solvent. Multiple parameters including theoretical drug loading (DL), presence of pSi, size of scCO2 vessel, PLGA type, and use of co-solvent were investigated with a view to obtaining high DL and a sustained-release for an extended period. The most important finding was that the use of a large scCO2 vessel (60 mL) resulted in a much higher encapsulation efficiency (EE) compared with a small vessel (12 mL). In addition, pre-loading ketamine into pSi slightly improved the level of drug incorporation (i.e. EE and DL). Although the in vitro release was mainly affected by the drug payload, the use of the large scCO2 vessel reduced the burst release and extended the release period for PLGA microparticles with 10% or 20% ketamine loading. Together, our findings provide valuable information for optimization of drug delivery systems prepared with the aid of scCO2. [ABSTRACT FROM AUTHOR]

Published
2022
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127. Correction to High F-Content Perfluoropolyether-Based Nanoparticles for Targeted Detection of Breast Cancer by 19F Magnetic Resonance and Optical Imaging

Author

Zhang, Cheng, primary, Moonshi, Shehzahdi Shebbrin, additional, Wang, Wenqian, additional, Ta, Hang Thu, additional, Han, Yanxiao, additional, Han, Felicity Y., additional, Peng, Hui, additional, Král, Petr, additional, Rolfe, Barbara E., additional, Gooding, J. Justin, additional, Gaus, Katharina, additional, and Whittaker, Andrew K., additional

Published
2020
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131. Rapid Generation of Block Copolymer Libraries Using Automated Chromatographic Separation

Author

Zhang, Cheng, primary, Bates, Morgan W., additional, Geng, Zhishuai, additional, Levi, Adam E., additional, Vigil, Daniel, additional, Barbon, Stephanie M., additional, Loman, Tessa, additional, Delaney, Kris T., additional, Fredrickson, Glenn H., additional, Bates, Christopher M., additional, Whittaker, Andrew K., additional, and Hawker, Craig J., additional

Published
2020
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132. Sulfoxide‐Containing Polymer‐Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation

Author

Qiao, Ruirui, primary, Fu, Changkui, additional, Li, Yuhuan, additional, Qi, Xiaole, additional, Ni, Dalong, additional, Nandakumar, Aparna, additional, Siddiqui, Ghizal, additional, Wang, Haiyan, additional, Zhang, Zheng, additional, Wu, Tingting, additional, Zhong, Jian, additional, Tang, Shi‐Yang, additional, Pan, Shuaijun, additional, Zhang, Cheng, additional, Whittaker, Michael R., additional, Engle, Jonathan W., additional, Creek, Darren J., additional, Caruso, Frank, additional, Ke, Pu Chun, additional, Cai, Weibo, additional, Whittaker, Andrew K., additional, and Davis, Thomas P., additional

Published
2020
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136. Low‐Fouling Fluoropolymers for Bioconjugation and In Vivo Tracking

Author

Fu, Changkui, primary, Demir, Baris, additional, Alcantara, Sheilajen, additional, Kumar, Vinod, additional, Han, Felicity, additional, Kelly, Hannah G., additional, Tan, Xiao, additional, Yu, Ye, additional, Xu, Weizhi, additional, Zhao, Jiacheng, additional, Zhang, Cheng, additional, Peng, Hui, additional, Boyer, Cyrille, additional, Woodruff, Trent M., additional, Kent, Stephen J., additional, Searles, Debra J., additional, and Whittaker, Andrew K., additional

Published
2020
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138. Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity

Author

Brighi, Caterina, primary, Reid, Lee, additional, Genovesi, Laura A, additional, Kojic, Marija, additional, Millar, Amanda, additional, Bruce, Zara, additional, White, Alison L, additional, Day, Bryan W, additional, Rose, Stephen, additional, Whittaker, Andrew K, additional, and Puttick, Simon, additional

Published
2020
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