Encapsulation of Biomacromolecules within Polymersomes by Electroporation

Wang, Linge; Chierico, Luca; Little, Daniel; Patikarnmonthon, Nisa; Zhou, Yang; Azzouz, Mimoun; Madsen, Jeppe; Armes, Steven P.; Battaglia, Giuseppe

doi:10.1002/anie.201204169

Cited by 104 publications

(80 citation statements)

References 22 publications

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“…and allow large amounts of biological molecules, alone and in combination, including proteins and nucleic acids, to be compartmentalized into nanoscale reactors (29,30). Furthermore, we have demonstrated (31)(32)(33)(34) that, when two different copolymers are used to form one polymersome, the resulting membrane segregates laterally into patterns whose topology is strictly controlled by the molar ratio of the two copolymers and eventually coarsen into two separate domains forming asymmetric polymersomes (35).…”

Section: Introductionmentioning

confidence: 85%

“…To a first approximation, we can thus infer that the PBO membrane is two orders of magnitude less permeable than the PDPA membrane. We can use such an asymmetric polymersome to encapsulate enzymes using a technique based on electroporation (30). We chose glucose oxidase to catalyze the glucose oxidation to form D-glucono-d-lactone and hydrogen peroxide and catalase to catalyze the decomposition of hydrogen peroxide into water and oxygen.…”

Section: Introductionmentioning

confidence: 99%

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Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Joseph

Contini

Cecchin

et al. 2016

Preprint

Self Cite

114

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In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano-or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro-and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Joseph

Contini

Cecchin

et al. 2016

Preprint

Self Cite

114

View full text Add to dashboard Cite

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“…These polymersomes are formed through the self-assembly of amphiphilic copolymers in aqueous media, 7 and combine the advantages of long-term stability with the potential to encapsulate a broad range of cargoes. [8][9][10] We have previously demonstrated that the pH sensitive block copolymer poly(2-(methacryloyloxy) ethyl-phosphorylcholine)-co-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) can combine specific cellular targeting efficiency (through the PMPC block and its affinity toward the scavenger receptor B1), 11 with effective endosomal escape and cytosolic delivery following internalisation (by the pH sensitive PDPA). 8,12 In this study, we describe the half life and bio-distribution of the PMPC-PDPA polymersomes in vivo, showing the dynamics of accumulation within different tissues.…”

Section: Introductionmentioning

confidence: 99%

Targeting mononuclear phagocytes for eradicating intracellular parasites

Rizzello

Robertson

Elks

et al. 2017

Preprint

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Mononuclear phagocytes such as monocytes, tissue-specific macrophages and dendritic cells are primary actors in both innate and adaptive immunity, as well as tissue homoeostasis. They have key roles in a range of physiological and pathological processes, so any strategy targeting these cells will have wide-ranging impact. These phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favouring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis, which is the most pandemic and one of the deadliest disease with one third of the world's population infected, and 1.8 million deaths worldwide in 2015. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to both circulating monocytes and resident macrophages, using pH sensitive nanoscopic polymersomes made of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-co-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA). Polymersome selectivity to mononuclear phagocytes is demonstrated and ascribed to the polymerised phosphorylcholine motifs affinity toward scavenger receptors. Finally, we demonstrate the successful exploitation of this targeting for the effective eradication of intracellular bacteria that cause tuberculosis Mycobacterium tuberculosis as well as other intracellular parasites including the Mycobacterium bovis, Mycobacterium marinum and the most common bacteria associated with antibiotic resistance, the Staphylococcus aureus.

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“…Although the mechanism of electroporation is largely unknown (mainly due to the short time scales and difficulty in probing pore formation), polymersome are believed to undergo similar poration to that observed in natural lipid cell membranes [40]. Furthermore, there are multiple parameters which can affect the outcome of electroporation.…”

Section: Forming Magnetopolymersomesmentioning

confidence: 99%

Synthesis of ABA Tri-Block Co-Polymer Magnetopolymersomes via Electroporation for Potential Medical Application

et al. 2015

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Abstract:The ABA tri-block copolymer poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) (PMOXA-PDMS-PMOXA) is known for its capacity to mimic a bilayer membrane in that it is able to form vesicular polymersome structures. For this reason, it is the subject of extensive research and enables the development of more robust, adaptable and biocompatible alternatives to natural liposomes for biomedical applications. However, the poor solubility of this polymer renders published methods for forming vesicles unreproducible, hindering research and development of these polymersomes. Here we present an adapted, simpler method for the production of PMOXA-PDMS-PMOXA polymersomes of a narrow polydispersity (45˘5.8 nm), via slow addition of aqueous solution to a new solvent/polymer mixture. We then magnetically functionalise these polymersomes to form magnetopolymersomes via in situ precipitation of iron-oxide magnetic nanoparticles (MNPs) within the PMOXA-PDMS-PMOXA polymersome core and membrane. This is achieved using electroporation to open pores within the membrane and to activate the formation of MNPs. The thick PMOXA-PDMS-PMOXA membrane is well known to be relatively non-permeable when compared to more commonly used di-block polymer membranes due a distinct difference in both size and chemistry and therefore very difficult to penetrate using standard biological methods. This paper presents for the first time the application of electroporation to an ABA tri-block polymersome membrane (PMOXA-PDMS-PMOXA) for intravesicular in situ precipitation of uniform MNPs (2.6˘0.5 nm). The electroporation process facilitates the transport of MNP reactants across the membrane yielding in situ precipitation of MNPs. Further to differences in length and chemistry, a tri-block polymersome membrane structure differs from a natural lipid or di-block polymer membrane and as such the application and effects of electroporation on this type of polymersome is entirely novel. A mechanism is hypothesised to explain the final structure and composition of these biomedically applicable tri-block magnetopolymersomes.

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Encapsulation of Biomacromolecules within Polymersomes by Electroporation

Cited by 104 publications

References 22 publications

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Targeting mononuclear phagocytes for eradicating intracellular parasites

Synthesis of ABA Tri-Block Co-Polymer Magnetopolymersomes via Electroporation for Potential Medical Application

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