Synthetic molecular motor activates drug delivery from polymersomes

Author:

Guinart Ainoa1ORCID,Korpidou Maria2ORCID,Doellerer Daniel1,Pacella Gianni3ORCID,Stuart Marc C. A.1ORCID,Dinu Ionel Adrian24ORCID,Portale Giuseppe3,Palivan Cornelia245ORCID,Feringa Ben L.13ORCID

Affiliation:

1. Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AG Groningen, The Netherlands

2. Department of Chemistry, University of Basel, BPR 1096, 4058 Basel, Switzerland

3. Faculty of Science and Engineering, Zernike Institute for Advanced Materials, University of Groningen, 9747 AG Groningen, The Netherlands

4. National Centre of Competence in Research-Molecular Systems Engineering, BioPark Rosental 1095 Basel, Switzerland

5. Swiss Nanoscience Institute, University of Basel, 4056 Basel, Switzerland

Abstract

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b -PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Funder

EC | ERC | HORIZON EUROPE European Research Council

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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