Design of "Smart" Nano-Scale Delivery Systems for Biomolecular Therapeutics

Hoffman, Amanda; Stayton, Patrick S.; El-Sayed, Mousa; Murthy, N. S.; Bulmuş, Volga; Lackey, Chantal A.; Cheung, Calvin

doi:10.1166/jbn.2007.031

Cited by 17 publications

(13 citation statements)

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“…79,84,86,87,219,322,380 It also enables the localization of a high concentration of drugs at a desired site of the body. Polymer-drug conjugates as prodrugs require the use of uniform polymers to be able to obtain a consistent in ViVo profile with an identifiable structure-activity correlation.…”

Section: Soluble Polymer-drug Conjugatesmentioning

confidence: 99%

Bioapplications of RAFT Polymerization

et al. 2009

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His Ph.D. was in collaboration with Solvay-Solexis and devoted to the synthesis of new graft copolymers using grafting "to". In 2005, he undertook a postdoctorate position with Dupont Performance and Elastomers (Willmington, United States) and Dr. B. Ameduri dealing with the synthesis of original fluorinated elastomers using controlled radical polymerization (e.g., iodine transfer polymerization). Since October 2006, he has been a senior research fellow under the direction of Prof. Thomas Davis in the Centre of Advanced Macromolecular Design (CAMD), University of New South Wales. His research interests mainly cover the preparation of well-defined polymers, protein-polymer conjugates, and hybrid organic-inorganic nanoparticles using controlled radical polymerization. He has coauthored over 40 peer-reviewed research papers, including 2 book chapters, and 2 patents. Volga Bulmus received her B.E. and M.Sc. in Chemical Engineering and her Ph.D. in bioengineering (Hacettepe University, Turkey), in 2000. She worked as a postdoctoral research fellow in the Bioengineering Department at the University of Washington between 2001 and 2003. In 2004, she was granted a highly competitive The University of New South Wales (UNSW) Vice Chancellor's Research Fellowship (Australia). In 2008, she was appointed as a Senior Lecturer at the School of Biotechnology and Biomolecular Sciences (UNSW). She is also an adjunct member of The Centre for Advanced Macromolecular Design (CAMD) at UNSW. Dr. Bulmus leads a group of 5-10 researchers working on the development of advanced polymers for biotechnology and biomedical applications. She has published over 45 peer reviewed research papers. Her research interests include design, synthesis, and evaluation of well-defined polymeric systems for nanobiotechnology and drug delivery applications ranging from antitumor chemotherapy and gene silencing to bioseparations and biosensors. Tom Davis has been an academic at UNSW for 17 years following a stint in industry as a research manager at ICI in the U.K. He has coauthored 315+ reviewed papers, patents, and book chapters. He is the Director of the Centre for Advanced Macromolecular Design (CAMD) at UNSWsa Centre with expertise in bio/organic polymer synthesis and polymerization kinetics. He is also a visiting Professor at the Institute for Materials Research & Engineering (IMRE) in Singapore. In 2005 he was awarded a Federation Fellowship by the Australian Research Council. He serves (or has served) on the editorial advisory boards of Macromolecules,

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Section: Soluble Polymer-drug Conjugatesmentioning

confidence: 99%

Bioapplications of RAFT Polymerization

et al. 2009

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“…Synthetic polymers have been investigated as facilitators of trehalose into cytoplasm by interacting with the cell membrane and temporarily increasing permeability [39][40][41][42][43][44] . Amphipathic polymers with weakly ionizable carboxyl acid side groups and hydrophobic side chains have garnered interest because of their high affinity for lipid membranes and ability to elevate membrane permeability by mimicking viral peptides as well as promote endosomal escape 62,63 . The most popular biopolymer investigated for trehalose-loading has been PP50, composed of biodegradable poly(L-lysine iso-phthalamide) (PLP) grafted with L-phenylalanine 64 .…”

Section: Polymers and Peptidesmentioning

confidence: 99%

Intracellular Delivery of Trehalose for Cell Banking

Stewart

2018

Langmuir

102

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Advances in stem cell technology and regenerative medicine have underscored the need for effective banking of living cells. Cryopreservation, using very low temperatures to achieve suspended animation, is widely used to store or bank cells for later use. This process requires the use of cryoprotective agents (CPAs) to protect cells against damage caused by the cooling and warming process. However, current popular CPAs like DMSO can be toxic to cells and must be thoroughly removed from cells before they can be used for research or clinical applications. Trehalose, a nontoxic sugar found in organisms capable of withstanding extreme cold or desiccation, has been explored as an alternative CPA. The disaccharide must be present on both sides of the cellular membrane to provide cryo-protection. However, trehalose is not synthesized by mammalian cells nor has the capability to diffuse through their plasma membranes. Therefore, it is crucial to achieve intracellular delivery of trehalose for utilizing the full potential of the sugar for cell banking. In this review, various methods that have been explored to deliver trehalose into mammalian cells for their banking at both cryogenic and ambient temperatures are surveyed. Among them, the nanoparticle-mediated approach is particularly exciting. Collectively, studies in the literature demonstrate the great potential of using trehalose as the sole CPA for cell banking, to facilitate the widespread use of living cells in modern medicine.

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“…35 In contrast, ATRP requires protection of acidic groups, and oen involves complications resulting from incomplete hydrolysis and lm detachment during the deprotection step. 36 Previously, homopolymers of 2-alkylacrylic acids with alkyl groups longer than methyl, [37][38][39][40][41] as well as copolymers of some of 2-alkylacrylic acids (aAA) with NIPAM 42 were studied in solution, and showed an interesting membrane disruption behavior at pH close to physiologic values, opening ways to use this effect for biological applications. Here, we present synthesis of such types of polymers at surfaces, and show that the use of EAA in copolymerization with NIPAM brushes enables pH and temperature response at neutral pH values even when EAA is fully ionized and its content in the copolymer is high.…”

Section: Introductionmentioning

confidence: 99%

Tunable pH and temperature response of weak polyelectrolyte brushes: role of hydrogen bonding and monomer hydrophobicity

Zhuk

et al. 2013

Soft Matter

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We report on weak polyacid brushes with highly tunable pH and temperature response characteristics. This was achieved by synthesizing a series of homo-and copolymers which contain 2-alkylacrylic acids (aAAs) of increased hydrophobicity, i.e. acrylic acid (AA), methacrylic acid (MAA), or 2-ethylacrylic acid (EAA), using surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. As revealed by contact angle measurements, in situ ellipsometry and AFM studies of brush swelling, the pH-response of PAA and PMAA brushes was similar, with brushes remaining highly swollen (swelling ratio 2.5-3.0) at low pH values. The PEAA brush, however, was unique as it showed low degrees of water uptake (<10%) at pH < 5 due to insolubility of this polyelectrolyte in acidic solutions, moderate swelling at high pH and relatively high (>70 ) contact angles in the entire pH region from 2 to 8. Copolymer brushes of aAAs with N-isopropylacrylamide (NIPAM), denoted as P(AA-co-NIPAM), P(MAA-co-NIPAM) and P(EAA-co-NIPAM), demonstrated dual pH and temperature response, which was strongly dependent on the type of aAA co-monomer. P(AA-co-NIPAM) and P(MAA-co-NIPAM) brushes underwent large-amplitude pHinduced changes in brush swelling and water contact angle in the range of pH from 3 to 6, and were only weakly responsive to temperature in the transition region. In contrast, more hydrophobic P(EAA-co-NIPAM) brushes demonstrated both pH and temperature responses at physiologically relevant neutral/ basic pH values even when the content of EAA units in the copolymer was as high as $50%. We discuss the role of inter-and intra-molecular hydrogen bonding and monomer hydrophobicity and ionization (quantified by FTIR) in determining pH ranges for brush response. These findings might enable control of molecular/cellular adhesion and flow at interfaces potentially useful in microfluidic and biomedical applications.

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Design of "Smart" Nano-Scale Delivery Systems for Biomolecular Therapeutics

Cited by 17 publications

References 0 publications

Bioapplications of RAFT Polymerization

Bioapplications of RAFT Polymerization

Intracellular Delivery of Trehalose for Cell Banking

Tunable pH and temperature response of weak polyelectrolyte brushes: role of hydrogen bonding and monomer hydrophobicity

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