A fast growing development in the field of nanomedicine is the application of autonomously propelled devices including micro-and nano-motors that are capable to convert various sources of energy into mechanical motion to harness non-Brownian motility for active cargo transport. A recent contribution of our group was the development of photothermally driven biodegradable hybrid nanomotors, based on polymeric vesicles, or polymersomes, which were able to traverse biological membranes and effectively penetrate tumor tissues, permitting active transport of molecular and macromolecular cargo.1 This platform offers promising applications in tissue penetration and cargo/drug delivery; however, encapsulating functional components such as fluorescent dyes or chemotherapeutics with a certain loading content are essential, not only to study the bio-distribution but also to achieve a more effective therapeutic performance. Besides, we are still faced with challenges that occur in conventional photo-therapeutics. For example, for photodynamic therapy, photosensitizers need to be incorporated which are effectively excited by irradiation and subsequently transform their energy to create singlet oxygen radicals. However, the efficiency of photosensitizers is often hampered by aggregation-induced quenching or photo-bleaching behavior. To provide a possible solution to circumvent these issues, intricately designed nanoparticles are needed. Particularly, through functional synergy between integrated physical elements, particle design can be kept simple and performance tailored towards the biomedical application. Aggregation-induced emission (AIE) is a feature that meets these criteria and we, therefore, embarked on the idea to integrate AIE functionality in our nanomotor systems.
Fig. 1 Design of synergistic AIE-transduced phototherapeutic nanomotors. The hemispherical Au shell is directly activated using two-photon near-infrared irradiation and indirectly activated via energy transduction from the AIE polymersome to result in enhanced phototaxis.
The first stage of our work involved the synthesis of amphiphilic block copolymers with an AIE photosensitizer block, which upon self-assembly would result in polymersomes with the AIE moieties included in the hydrophobic membrane. The optimal procedure involved an approach in which we used a pentafluorophenyl based block copolymer which could be modified post-polymerization with the desired AIE moiety.2 We obtained well-defined block-co-polymers, which met the criteria for controlled self-assembly. Spherical polymersomes were prepared via a solvent switch method, which was extensively characterized via light scattering techniques and electron microscopy. After a sputter coating procedure, hybrid polymersomes comprising hemispherical Au shells were prepared. The hybrid polymersomes displayed several intriguing properties. For instance, the asymmetric Au nanoshell enabled the hybrid particles to harness two-photon near-infrared (TP-NIR) irradiation and produce a thermal gradient, triggering autonomous propulsion allowing the particles to be used as photo-activated nanomotors. The plasmonic heating effect also resulted in a photo-thermal therapy. Besides, the AIE moieties allowed facile tracking of the nanomotors with confocal imaging and enabled the production of reactive oxygen species (ROS) through two-photon light irradiation, for photodynamic therapy. Furthermore, both functional modalities did not simply act concurrently but also in unison – whereby the AIE capacity transduced TP-NIR irradiation into plasmonic energy and, through its highly stable fluorescence, photothermally activated the Au layer to provide enhanced motile behavior to increase the therapeutic effect. Finally, these functional nanomotors were demonstrated to be a powerful tool for site-specific therapy, triggered by an externally controlled physical stimulus (TP-NIR) without the need for chemical signaling.
The project was challenging and required collaborations with a multidisciplinary team. Working intensively together with researchers with backgrounds in synthetic chemistry, biomedical engineering, and physics, allowed us to push the boundaries of nanomedical engineering and photo-therapy. Although nanomotors have already emerged as a promising platform in nanomedicine, we are confident that our design with its integrated functionalities will attract a broad readership and contribute to the growth of this field. We sincerely hope that this could contribute to the design of functional photo-therapeutic systems and inspire researchers in different fields to work together, pushing the boundaries of nanomedicine and providing promising utilities for future clinic use.
To learn more about our work, please read our article "Photoactivated Nanomotors via Aggregation Induced Emission for Enhanced Phototherapy" in Nature Communications (https://doi.org/10.1038/s41467-021-22279-w).
- Shao, J. X.; Cao, S. P.; Williams, D. S.; Abdelmohsen, L. K. E. A.; van Hest, J. C. M., Photoactivated Polymersome Nanomotors: Traversing Biological Barriers. Angew. Chem. Int. Ed. 2020, 59 (39), 16918-16925.
- Cao, S. P.; Abdelmohsen, L. K. E. A.; Shao, J. X.; van den Dikkenberg, J.; Mastrobattista, E.; Williams, D. S.; van Hest, J. C. M., pH-Induced Transformation of Biodegradable Multilamellar Nanovectors for Enhanced Tumor Penetration. Acs Macro Letters 2018, 7 (11), 1394-1399.