Polymer Vesicles

Discher, Dennis E.; Eisenberg, Adi

doi:10.1126/science.1074972

Cited by 3,491 publications

(3,283 citation statements)

References 47 publications

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“…These screening experiments also revealed that ELP BC s with a hydrophilic-tohydrophobic ratio between 1:2 and 2:1 formed nanoparticles (1:2 ≤ ratio ≤ 2:1). This lower threshold of a 1:2 ratio is similar to an f value of 33%, which was shown by Discher et al 36 to form vesicles. Increasing the hydrophilic-to-hydrophobic ratio above 1:2 also resulted in nanoparticle formation, analogous to Discher's findings36.…”

Section: Thermal Properties Of Elp Bc Ssupporting

confidence: 84%

“…In addition, the size of the micelle was controlled by both the total length of the ELP BC and the hydrophilic-to-hydrophobic block ratio supported by the models of Israelachvili et al 42 and Discher et al 36 . For example, increasing the total length while maintaining a constant block ratio increased the micelle size from 29.1 nm for ELP-64/60 (length = 120) to 36.6 nm for ELP-96/90 (length = 180).…”

Section: Light Scattering Of Elp Bc Smentioning

confidence: 96%

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Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

et al. 2007

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We report herein thermally responsive elastin-like polypeptides (ELPs) in a linear AB diblock architecture with an N-terminal peptide ligand that self-assemble into spherical micelles when heated slightly above body temperature. A series of 10 ELP block copolymers (ELP BC s) with different molecular weights and hydrophilic-to-hydrophobic block ratios were genetically synthesized by recursive directional ligation. The self-assembly of these polymers from unimers into micelles was investigated by light scattering, fluorescence spectroscopy and cryo-TEM. These ELP BC s undergo two phase transitions as a function of solution temperature: a unimer to spherical micelle transition at an intermediate temperature, and a micelle to bulk aggregate transition at a higher temperature when the hydrophilic-to-hydrophobic block ratio is between 1:2 and 2:1. The critical micelle temperature is controlled by the length of the hydrophobic block and the size of the micelle is controlled by both the total ELP BC length and hydrophilic-to-hydrophobic block ratio. These polypeptide micelles display a critical micelle concentration in the range of 4-8 μM demonstrating high stability of these structures. These studies have also identified a subset of ELP BC s bearing terminal peptide ligands that are capable of forming multivalent spherical micelles that present multiple copies of the ligand on their corona in the clinically relevant temperature range of 37-42 °C and target cancer cells. These ELP BC s may be useful for drug targeting by thermally triggered multivalency. More broadly, the design rules uncovered by this study should be applicable to the design of other thermally reversible nanoparticles for diverse applications in medicine and biology.

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Section: Thermal Properties Of Elp Bc Ssupporting

confidence: 84%

Section: Light Scattering Of Elp Bc Smentioning

confidence: 96%

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

et al. 2007

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“…Synthetic polymers are showing great promise 11 particularly in recent years where liposome and polymer technology have merged in the design of self-assembling membrane-enclosed structures comprised of block copolymers called polymersomes 12,13,14 .…”

Section: Introductionmentioning

confidence: 99%

“…Advances in polymer synthesis techniques have enabled polymers to be designed with optimum properties for drug delivery including high molecular weights, enhanced stability, side chain functionality and more importantly, responsiveness [12][13][14]16 .…”

Section: Introductionmentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumour cells, reducing off-target toxicity that often compromises anti-cancer treatment. Here we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anti-cancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalised by HNSCC cells compared to normal oral cells. Polymersome cellular up-take was found to be mediated by class B scavenger receptors.We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumour models, PMPC-PDPA polymersomes were able to penetrate deep into the centre of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC.Moreover, the preferential internalisation of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumours.3

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“…This can be achieved using transmembrane proteins with the appropriate reaction centers able to catalyse several reactions simultaneously (two in our example). Potential scenarios might use polymer vesicles instead of liposomes (Discher and Eisenberg, 2002). After cellular division, each daughter cell has only one metabolic center.…”

Section: Article In Pressmentioning

confidence: 99%

Protocell self-reproduction in a spatially extended metabolism–vesicle system

Macía

Solé

2007

Journal of Theoretical Biology

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Cellular life requires the presence of a set of biochemical mechanisms in order to maintain a predictable process of growth and division. Several attempts have been made towards the building of minimal protocells from a top-down approach, i.e. by using available biomolecules. This type of synthetic approach has so far been only partially successful, and appropriate models of the synthetic protocell cycle might be needed to guide future experiments. In this paper, we present a simple biochemically and physically feasible model of cell replication involving a discrete semi-permeable vesicle with an internal minimal metabolism involving two reactive centers. It is shown that such a system can effectively undergo a whole cell replication cycle. The model can be used as a basic framework to model whole protocell dynamics including more complex sets of reactions. The possible implementation of our design in future synthetic protocells is outlined. r

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Polymer Vesicles

Cited by 3,491 publications

References 47 publications

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Protocell self-reproduction in a spatially extended metabolism–vesicle system

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