Synthetic molecular motor activates drug delivery from polymersomes

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.

FAP Targeting of Photosensitizer-Loaded Polymersomes for Increased Light-Activated Cell Killing

“…Pol-Atto633 exhibited a slightly negative zeta potential (−4.0 ± 0.5 mV), in good agreement with the values obtained for polymersomes assembled using mixtures of PDMS- b -PMOXA copolymers (Table S2). We calculated an encapsulation efficiency of Atto633 of 47% ± 3%, assessed by UV spectroscopy, which is in agreement with values obtained for the encapsulation of small molecular weight molecules inside polymersomes during the self-assembly process. , …”

“…41 We calculated an encapsulation efficiency of Atto633 of 47% ± 3%, assessed by UV spectroscopy, which is in agreement with values obtained for the encapsulation of small molecular weight molecules inside polymersomes during the self-assembly process. 42,43 We then coupled the fibroblast activation protein inhibitor (FAPi; Figure 1a) to the azide-functional groups exposed at the surface of polymersomes by click chemistry. We used a DIBO-functionalized, poly(ethylene glycol)-linked FAPi molecule (DIBO-PEG 3 -FAPi) 31 where the strained cyclooctyne group allowed the conjugation of FAPi to the azide-terminated copolymer by SPAAC reaction.…”

Light-activation of molecular motors in polymersomes

“…However, the recent results reported by Guinart show that at much larger concentrations (50 mol%), the rotation of a motor can induce the disassembly of larger polymersomes (PDMS 25 - b -PMOXA 10 ). 22…”

“…Recently, Guinart et al published a study showing that the light irradiation of molecular motors can cause the complete disassembly of polymersomes of PDMS 25 - b -PMOXA 10 diblock copolymers and activate the delivery of drugs. 22 They achieved this by loading up to 50 mol% of their motor in polymersomes of ≈150 nm diameter. The authors demonstrated the first step of the motor's rotary cycle (the E / Z photoisomerization) in the polymersome, but the thermal helix inversion step was not investigated.…”

Molecular Machines For The Control Of Transmembrane Transport

“…Feringa and co-workers have investigated the use of molecular motors for the controlled release of cargo from lipid-bound compartments, with the view to develop targeted drug delivery vehicles . Incorporating motors within amphiphilic molecules has been shown to generate micelle and vesicle self-assembled structures, to allow the investigation of their dynamic behavior in biologically relevant media. , Hydrophobic motors have also been incorporated within lipid membranes, where 365 nm light irradiation led to the release of molecular cargo from DOPC (unsaturated lipid) vesicles .…”