H2020Individual fellowship2020–2022

AutoPolymer · Autocatalytic Self-Synthesising Polymersomes

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-08-01 → 2022-07-31
EU contribution
€212,934
Participants
1
Scheme
MSCA-IF

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Results in brief

Autocatalytic Self-Synthesising Polymersomes

Is there life beyond biology? How does chemistry become biology? Beyond formulating questions that are intellectually challenging, the main objective of this proposal was to find features of life in artificial synthetic constructs to generate technologies at the Living/Non-Living interface. The work employed cell units as a source of inspiration, which act as highly cooperative machinery to work in unison and produce cellular functions such as growth, communication, nourishment, or reproduction. In order to stay alive and produce their complex functions, they continuously produce energy gradients and metabolite transport in a state that is out-of-equilibrium with their environment. The overall goal of AutoPolymer has been to generate polymeric nanoparticles with capacity to undergo these out-of-equilibrium states and perform functions that remind us to living systems. For example, predatory particle populations that could feed from prey particle populations were explored in an aim to establish systems that could self-synthesise in the near future. In another example, the project took inspiration from the circadian rhythm which uses day and night cycles to regulate the alternation of metabolic activity. In these processes, the oscillation of metabolite concentrations is controlled by chemical hierarchical networks of independent oscillators that communicate and regulate each other to adapt to light intensity. By generating out-of-equilibrium polymer-enzyme hybrids that could catalyse antagonistic reactions in response to light, oscillations of chemical concentrations could be achieved. Overall, these results establish the developed chemical platform as a highly promising proof-of-concept to achieve systems at the Living/Non-Living interface that can manipulate cell activity finding applications in the modulation of bioreactors for the synthesis of compounds of industrial interest, or to generate motile, self-adaptive biomedical implants. The multidisciplinary nature of this highly ambitions project was strongly supported by its localisation within the world-renowned Stevens Group at Imperial College London. The diverse nature of the project required input from a number of personnel within the Group with research backgrounds across chemistry, materials science, cell biology, molecular dynamics simulations, and spectroscopy and was crucial to meeting project outcomes. Ongoing collaborations which have been established as a result of this fellowship will continue to drive this work towards future applications.

Data: CORDIS, © European Union

Project objective

Polymersomes, hollow polymer vesicles made from assembled amphiphilic block copolymers, are interesting systems for drug delivery as they can be synthesised to be biocompatible, biodegradable, and/or stimuli-responsive. A main limitation of all drug delivery vehicles is that they require multiple steps of synthesis and a posterior self-assembly process that generates low yields and high quantities of non-encapsulated waste, limiting industrial scalability. Being hosted in the Stevens Group (www.stevensgroup.org, recognised with over 30 major awards), AutoPolymer aims at generating a versatile platform for the generation of polymersome-based drug delivery vehicles which can self-replicate by synthesising amphiphilic block copolymers in the lumen, with the future perspective of co synthesising encapsulated therapeutic agents. The strategy builds on finding bioinspiration in nature, mimicking the autosynthesis of structural components of cells through the mitosis process. This will be achieved by generating enzyme-containing polymersomes which have the capacity to biocatalyse polymerisation reactions. The polymers will be synthesised in the lumen of the polymersomes and will then migrate and assemble to the existing membrane. This will allow for membrane surface area growth and posterior binary fission splitting the encapsulated contents. The incorporation of light responsive chemical motifs to the polymersomes throughout their autosynthesis will be studied to render light-responsive drug delivery vehicles. The polymersomes will be tested for their therapeutic effects on cell lines. The approach is highly versatile and could, in principle, be used for a great variety of chemical compositions and encapsulated therapeutic agents. The potential of the project will be evaluated through the outstanding infrastructure of the Stevens Group.

Original text from CORDIS.

Participants

  • IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonCoordinatorUnited Kingdom

Links

Data: CORDIS, © European Union