Publications by authors named "Daniela A Wilson"

65 Publications

Generating biomembrane-like local curvature in polymersomes via dynamic polymer insertion.

Nat Commun 2021 04 14;12(1):2235. Epub 2021 Apr 14.

Institute for Molecules and Materials, Radboud University, Nijmegen, the Netherlands.

Biomembrane curvature formation has long been observed to be essential in the change of membrane morphology and intracellular processes. The significant importance of curvature formation has attracted scientists from different backgrounds to study it. Although magnificent progress has been achieved using liposome models, the instability of these models restrict further exploration. Here, we report a new approach to mimic biomembrane curvature formation using polymersomes as a model, and poly(N-isopropylacrylamide) to induce the local curvature based on its co-nonsolvency phenomenon. Curvatures form when poly(N-isopropylacrylamide) becomes hydrophobic and inserts into the membrane through solvent addition. The insertion area can be fine-tuned by adjusting the poly(N-isopropylacrylamide) concentration, accompanied by the formation of new polymersome-based non-axisymmetric shapes. Moreover, a systematic view of curvature formation is provided through investigation of the segregation, local distribution and dissociation of inserted poly(N-isopropylacrylamide). This strategy successfully mimicks biomembrane curvature formation in polymersomes and a detailed observation of the insertion can be beneficial for a further understanding of the curvature formation process. Furthermore, polymer insertion induced shape changing could open up new routes for the design of non-axisymmetric nanocarriers and nanomachines to enrich the boundless possibilities of nanotechnology.
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http://dx.doi.org/10.1038/s41467-021-22563-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046815PMC
April 2021

Control the Neural Stem Cell Fate with Biohybrid Piezoelectrical Magnetite Micromotors.

Nano Lett 2021 Apr 13;21(8):3518-3526. Epub 2021 Apr 13.

School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

Inducing neural stem cells to differentiate and replace degenerated functional neurons represents the most promising approach for neural degenerative diseases including Parkinson's disease, Alzheimer's disease, etc. While diverse strategies have been proposed in recent years, most of these are hindered due to uncontrollable cell fate and device invasiveness. Here, we report a minimally invasive micromotor platform with biodegradable helical () as the framework and superparamagnetic FeO nanoparticles/piezoelectric BaTiO nanoparticles as the built-in function units. With a low-strength rotational magnetic field, this integrated micromotor system can perform precise navigation in biofluid and achieve single-neural stem cell targeting. Remarkably, by tuning ultrasound intensity, thus the local electrical output by the motor, directed differentiation of the neural stem cell into astrocytes, functional neurons (dopamine neurons, cholinergic neurons), and oligodendrocytes, can be achieved. This micromotor platform can serve as a highly controllable wireless tool for bioelectronics and neuronal regenerative therapy.
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http://dx.doi.org/10.1021/acs.nanolett.1c00290DOI Listing
April 2021

Exploring New Horizons in Liquid Compartmentalization via Microfluidics.

Biomacromolecules 2021 May 9;22(5):1759-1769. Epub 2021 Apr 9.

Institute of Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.

Spatial organization of cellular processes is crucial to efficiently regulate life's essential reactions. Nature does this by compartmentalization, either using membranes, such as the cell and nuclear membrane, or by liquid-like droplets formed by aqueous liquid-liquid phase separation. Aqueous liquid-liquid phase separation can be divided in two different phenomena, associative and segregative phase separation, of which both are studied for their membraneless compartmentalization abilities. For centuries, segregative phase separation has been used for the extraction and purification of biomolecules. With the emergence of microfluidic techniques, further exciting possibilities were explored because of their ability to fine-tune phase separation within emulsions of various compositions and morphologies and achieve one of the simplest forms of compartmentalization. Lately, interest in aqueous liquid-liquid phase separation has been revived due to the discovery of membraneless phases within the cell. In this Perspective we focus on segregative aqueous phase separation, discuss the theory of this interesting phenomenon, and give an overview of the evolution of aqueous phase separation in microfluidics.
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http://dx.doi.org/10.1021/acs.biomac.0c01796DOI Listing
May 2021

Membrane folding and shape transformation in biomimetic vesicles.

Soft Matter 2021 Feb 19;17(7):1724-1730. Epub 2021 Jan 19.

Systems Chemistry Department, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.

Polymeric self-assembled structures have been a topic of interest in the last few decades, specifically for the use of biomedical applications, such as drug delivery. It is exciting to investigate the formation of various shapes and sizes of such structures, as the morphology is crucial for their function. In this manuscript the important factors to control the morphology during self-assembly and subsequent shape transformation processes are discussed. We describe the main parameters to control and show the practical application of these parameters on biodegradable amphiphilic PEG-PDLLA block-copolymers. Thereby a variety of different morphologies, including micelles, worms, LCVs, discs, rods, stomatocytes, nested vesicles, and spherical vesicles of various sizes are created using only four diblock-copolymers and with careful tuning of two organic solvents. Further advances will lead to formation of more complex structures.
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http://dx.doi.org/10.1039/d0sm01932aDOI Listing
February 2021

Supramolecular nanomotors with "pH taxis" for active drug delivery in the tumor microenvironment.

Nanoscale 2020 Nov;12(44):22495-22501

Institute of Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.

Self-propelled nanomotors demonstrating autonomous motion in biologically relevant fuel are currently being studied to overcome the use of external physical or chemical stimuli as precise delivery agents. In this context, the tumor microenvironment (TME) with slightly acidic pH is used for developing cargo-releasing artificial systems triggered by such conditions. However, there is still a need for fabrication of smart nanomotors that can sense the acidic pH prevalent in the TME rather than using an external fuel source for selective activation and thereafter migrating towards tumors for active drug delivery. Herein, supramolecular assembly-based nanomotors are fabricated by in-situ grown CaCO3 nanoparticles and studied for their motility behaviour in endogenously generated acidic pH by HeLa cells and further exploited as an active delivery vehicle for DOX molecules to the cells for their anticancer efficacy. The nanomotors are activated in slightly acidic pH showcasing "pH taxis" towards tumor cells without the need for any sophisticated/complicated technologies or an external fuel source for active and targeted delivery of drugs.
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http://dx.doi.org/10.1039/d0nr04415fDOI Listing
November 2020

Leveraging synthetic particles for communication: from passive to active systems.

Nanoscale 2020 Oct;12(41):21015-21033

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

Communication is one of the most remarkable behaviors in the living world. It is an important prerequisite for building an artificial cell which can be considered as alive. Achieving complex communicative behaviors leveraging synthetic particles will likely fill the gap between artificial vesicles and natural counterpart of cells and allow for the discovery of new therapies in medicine. In this review, we highlight recent endeavors for constructing communication with synthetic particles by revealing the principles underlying the communicative behaviors. Emergent progress using active particles to achieve communication is also discussed, which resembles the dynamic and out-of-equilibrium properties of communication in nature.
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http://dx.doi.org/10.1039/d0nr05675hDOI Listing
October 2020

Enzyme catalysis powered micro/nanomotors for biomedical applications.

J Mater Chem B 2020 08;8(33):7319-7334

Institute of Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.

With recent developments in the field of autonomous motion for artificial systems, many researchers are focusing on their biomedical application for active and targeted delivery. In this context, enzyme powered motors are at the forefront since they can utilize physiologically relevant fuels as their substrate and carry out catalytic reactions to power motion under in vivo conditions. This review focuses on the design and fabrication of enzyme powered motors together with their propulsion mechanism by using fuels present in biological environments. In addition, the recent advances in the field of enzyme powered motors for biomedical applications have been discussed together with the parameters that need to be considered for designing such systems. We believe that this review will provide insights and better understanding for the development of next generation biomedical technologies based on enzyme powered motors.
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http://dx.doi.org/10.1039/d0tb01245aDOI Listing
August 2020

Two-Photon-Induced [2 + 2] Cycloaddition of Bis-thymines: A Biocompatible and Reversible Approach.

ACS Omega 2020 May 12;5(20):11547-11552. Epub 2020 May 12.

Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Heverlee, Belgium.

Despite having great value across a wide variety of scientific fields, two-photon polymerizations currently suffer from two significant problems: the need for photoinitiators, which generate toxic side products, and the irreversibility of the process. Hence, the design of a versatile approach that circumvents these issues represents a major scientific challenge. Herein, we report a two-photon absorption strategy where reversible [2 + 2] cycloaddition of bis-thymines was achieved without the need for any photoinitiator. The cycloaddition and cycloreversion reactions could be induced by simply changing the irradiation wavelength, and repeated writing and erasing cycles were performed. The simplicity, reversibility, and biocompatibility of this strategy open up a whole new toolbox for applications across a wide variety of scientific fields.
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http://dx.doi.org/10.1021/acsomega.0c00770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254774PMC
May 2020

Self-Propelled PLGA Micromotor with Chemotactic Response to Inflammation.

Adv Healthc Mater 2020 04 6;9(7):e1901710. Epub 2020 Mar 6.

Institute for Molecules and Materials Radboud University, 6525 AJ, Nijmegen, The Netherlands.

Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site-specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug-loaded biodegradable micromotors showing self-propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters-stimulated macrophages are reported. The drug-loaded poly(lactic-co-glycolic acid) micromotors with asymmetric coverage of enzyme (patch-like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high-performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters-stimulated macrophages.
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http://dx.doi.org/10.1002/adhm.201901710DOI Listing
April 2020

Micro-/Nanomotors toward Biomedical Applications: The Recent Progress in Biocompatibility.

Small 2020 07 4;16(27):e1906184. Epub 2020 Mar 4.

School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.

Inspired by the highly versatile natural motors, artificial micro-/nanomotors that can convert surrounding energies into mechanical motion and accomplish multiple tasks are devised. In the past few years, micro-/nanomotors have demonstrated significant potential in biomedicine. However, the practical biomedical applications of these small-scale devices are still at an infant stage. For successful bench-to-bed translation, biocompatibility of micro-/nanomotor systems is the central issue to be considered. Herein, the recent progress in micro-/nanomotors in biocompatibility is reviewed, with a special focus on their biomedical applications. Through close collaboration between researches in the nanoengineering, material chemistry, and biomedical fields, it is expected that a promising real-world application platform based on micro-/nanomotors will emerge in the near future.
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http://dx.doi.org/10.1002/smll.201906184DOI Listing
July 2020

Modular Approach to the Functionalization of Polymersomes.

Biomacromolecules 2020 05 19;21(5):1853-1864. Epub 2020 Feb 19.

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

Functionalizing polymersomes remains a challenge due to the limitation in reaction conditions applicable to the chemistry on the surface, hindering their application for selective targeting. In order to overcome this limitation, functionalization can be introduced right before the self-assembly. Here, we have synthesized a library (32 examples) of PEG--PS and PEG--PDLLA with various functional groups derived from the amine-functionalized polymers, leading to functionally active polymersomes. We show that polymersome formation is possible via the general method with all functionalized groups and that these handles are present on the surface and are able to undergo reactions. Additionally, this methodology provides a general synthetic tool to tailor the functional group of the polymersome right before self-assembly, without limitation on the reaction conditions.
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http://dx.doi.org/10.1021/acs.biomac.9b01734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218747PMC
May 2020

Spatial control over catalyst positioning on biodegradable polymeric nanomotors.

Nat Commun 2019 11 22;10(1):5308. Epub 2019 Nov 22.

Systems Chemistry Department, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.

Scientists over the world are inspired by biological nanomotors and try to mimic these complex structures. In recent years multiple nanomotors have been created for various fields, such as biomedical applications or environmental remediation, which require a different design both in terms of size and shape, as well as material properties. So far, only relatively simple designs for synthetic nanomotors have been reported. Herein, we report an approach to create biodegradable polymeric nanomotors with a multivalent design. PEG-PDLLA (poly(ethylene glycol)-b-poly(D,L-lactide)) stomatocytes with azide handles were created that were selectively reduced on the outside surface by TCEP (tris(2-carboxyethyl)phosphine) functionalized beads. Thereby, two different functional handles were created, both on the inner and outer surface of the stomatocytes, providing spatial control for catalyst positioning. Enzymes were coupled on the inside of the stomatocyte to induce motion in the presence of fuel, while fluorophores and other molecules can be attached on the outside.
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http://dx.doi.org/10.1038/s41467-019-13288-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876569PMC
November 2019

Nonequilibrium Reshaping of Polymersomes Polymer Addition.

ACS Nano 2019 11 11;13(11):12767-12773. Epub 2019 Nov 11.

Institute for Molecules and Materials , Radboud University , Heyendaalseweg 135 , 6525 AJ Nijmegen , The Netherlands.

Polymersomes are a class of artificial liposomes, assembled from amphiphilic synthetic block copolymers, holding great promise toward applications in nanomedicine. The diversity in polymersome morphological shapes and, in particular, the precise control of these shapes, which is an important aspect in drug delivery studies, remains a great challenge. This is due to a lack of general methodologies that can be applied and the inability to capture the morphologies at the nanometer scale. Here, we present a methodology that can accurately control the shape of polymersomes the addition of polyethylene glycol (PEG) under nonequilibrium conditions. Various shapes including spheres, ellipsoids, tubes, discs, stomatocytes, nests, stomatocyte-in-stomatocytes, disc-in-discs, and large compound vesicles (LCVs) can be uniformly captured by adjusting the water content and the PEG concentration. Moreover, these shapes undergo nonequilibrium changes in time, which is reflected in their phase diagram changes. This research provides a universal tool to fabricate all shapes of polymersomes by controlling three variables: water content, PEG concentration, and time. The use of the biofriendly polymer PEG enables the application of this methodology in the field of nanomedicine.
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http://dx.doi.org/10.1021/acsnano.9b04740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887890PMC
November 2019

Stimulus-responsive nanomotors based on gated enzyme-powered Janus Au-mesoporous silica nanoparticles for enhanced cargo delivery.

Chem Commun (Camb) 2019 Oct;55(87):13164-13167

Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Spain. and Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Valencia, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, València, Spain and CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.

Here we report functional stimulus-responsive nanomotors based on Janus Au-mesoporous silica nanoparticles capable of self-propelling via the biocatalytic conversion of chemical fuel, that read information from the environment (the presence of glutathione) and accordingly deliver a cargo.
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http://dx.doi.org/10.1039/c9cc07250kDOI Listing
October 2019

Tailoring Polymersome Shape Using the Hofmeister Effect.

Biomacromolecules 2020 01 11;21(1):89-94. Epub 2019 Oct 11.

Radboud University , Institute for Molecules and Materials , Heyendaalseweg 135 , 6525 AJ , Nijmegen , The Netherlands.

Reshaping polymersomes remains a challenge for both size and shape control, methodology development, and mechanism understanding, which hindered their application in nanomedicine and nanomachine. Unlike liposome, polymersomes are capable of maintaining their shape due to their rigid and glassy membrane. Here we use the Hofmeister effect to guide the shape control of polymersome by tuning the ion type and concentration. Multiple morphologies such as ellipsoid, tube, disc, stomatocytes, and large compound vesicles are found. These results give evidence of demonstrating that the shape changes are not only induced by osmotic pressure, but also by the interaction with the polymersome membranes. Additionally, this methodology provides a general tool to tailor the shape of polymersome into various morphologies.
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http://dx.doi.org/10.1021/acs.biomac.9b00924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961129PMC
January 2020

Enzyme-Powered Nanomotors with Controlled Size for Biomedical Applications.

ACS Nano 2019 09 27;13(9):10191-10200. Epub 2019 Aug 27.

Institute for Molecules and Materials , Radboud University , Heyendaalseweg 135 , 6525 AJ Nijmegen , The Netherlands.

Self-propelled motors have been developed with promising potential for medical applications. However, most of them have a size range at the microscale, which limits their further research for experiments. Previously, our group developed nanoscaled motors with a size of around 400 nm with several merits, for example, delivering both hydrophobic and hydrophilic drugs/proteins, using biocompatible fuels while being able to control their motion, and showing adaptive changes of their speed and navigation to changes in the environment. It is also well-known that nanoparticles that are around 20-200 nm in size have advantages in overcoming cellular barriers and being internalized into cells. Therefore, lowering the size range of this stomatocyte nanomotor is crucial. However, the strict control of the size of vesicles in such a low regime as well as their shape transformation into folded stomatocyte structures is not trivial. In this study, we fabricated ultrasmall stomatocyte polymersomes with the size of around 150 nm, which could be a promising carrier for biomedical purposes. We demonstrated that the addition of PEG additive allows for both shape transformation of small polymersomes into stomatocytes and encapsulation of biologics. Biocatalyst catalase was encapsulated in the inner compartment of the nanomotor, protecting the enzyme while providing enough thrust to propel the motors. The ultrasmall stomatocyte motor system allowed propelled motion by converting HO into O in the presence of only 2 mM HO, and the velocity of motors correlated to the O production. Compared to small stomatocyte nanomotors, ultrasmall stomatocyte motors demonstrate enhanced penetration across the vasculature model and increased uptake by HeLa cells in the presence of fuel.
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http://dx.doi.org/10.1021/acsnano.9b03358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764168PMC
September 2019

Thermoresponsive Brushes Facilitate Effective Reinforcement of Calcium Phosphate Cements.

ACS Appl Mater Interfaces 2019 Jul 16;11(30):26690-26703. Epub 2019 Jul 16.

Department of Regenerative Biomaterials , Radboud University Medical Center , 6525 EX Nijmegen , The Netherlands.

Calcium phosphate ceramics are frequently applied to stimulate regeneration of bone in view of their excellent biological compatibility with bone tissue. Unfortunately, these bioceramics are also highly brittle. To improve their toughness, fibers can be incorporated as the reinforcing component for the calcium phosphate cements. Herein, we functionalize the surface of poly(vinyl alcohol) fibers with thermoresponsive poly(-isopropylacrylamide) brushes of tunable thickness to improve simultaneously fiber dispersion and fiber-matrix affinity. These brushes shift from hydrophilic to hydrophobic behavior at temperatures above their lower critical solution temperature of 32 °C. This dual thermoresponsive shift favors fiber dispersion throughout the hydrophilic calcium phosphate cements (at 21 °C) and toughens these cements when reaching their hydrophobic state (at 37 °C). The reinforcement efficacy of these surface-modified fibers was almost double at 37 versus 21 °C, which confirms the strong potential of thermoresponsive fibers for reinforcement of calcium phosphate cements.
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http://dx.doi.org/10.1021/acsami.9b08311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676411PMC
July 2019

Fabrication of Self-Propelled Micro- and Nanomotors Based on Janus Structures.

Chemistry 2019 Jul 21;25(37):8663-8680. Epub 2019 May 21.

School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug, Screening Southern Medical University, Guangzhou, 510515, P.R. China.

Delicate molecular and biological motors are tiny machines capable of achieving numerous vital tasks in biological processes. To gain a deeper understanding of their mechanism of motion, researchers from multiple backgrounds have designed and fabricated artificial micro- and nanomotors. These nano-/microscale motors can self-propel in solution by exploiting different sources of energy; thus showing tremendous potential in widespread applications. As one of the most common motor systems, Janus motors possess unique asymmetric structures and integrate different functional materials onto two sides. This review mainly focuses on the fabrication of different types of micro- and nanomotors based on Janus structures. Furthermore, some challenges still exist in the implementation of Janus motors in the biomedical field. With such common goals in mind, it is expected that the elaborate and multifunctional design of Janus motors will overcome their challenges in the near future.
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http://dx.doi.org/10.1002/chem.201900840DOI Listing
July 2019

Motion Control of Polymeric Nanomotors Based on Host-Guest Interactions.

Angew Chem Int Ed Engl 2019 06 20;58(26):8687-8691. Epub 2019 May 20.

Institute for Molecules and Materials, Radboud University, Nijmegen, 6525, AJ, The Netherlands.

Controlling the motion of artificial self-propelled micro- and nanomotors independent of the fuel concentration is still a great challenge. Here we describe the first report of speed manipulation of supramolecular nanomotors via blue light-responsive valves, which can regulate the access of hydrogen peroxide fuel into the motors. Light-sensitive polymeric nanomotors are built up via the self-assembly of functional block copolymers, followed by bowl-shaped stomatocyte formation and incorporation of platinum nanoparticles. Subsequent addition of β-cyclodextrin (β-CD) leads to the formation of inclusion complexes with the trans-isomers of the azobenzene derivatives grafted from the surfaces of the stomatocytes. β-CDs attachment decreases the diffusion rate of hydrogen peroxide into the cavities of the motors because of partly blocking of the openings of the stomatocyte. This results in a lowering of the speed of the nanomotors. Upon blue light irradiation, the trans-azobenzene moieties isomerize to the cis-form, which lead to the detachment of the β-CDs due to their inability to form complexes with the cis-isomer. As a result, the speed of the nanomotors increases accordingly. Such a conformational change provides us with the unique possibility to control the speed of the supramolecular nanomotor via light-responsive host-guest complexation. We envision that such artificial responsive nano-systems with controlled motion could have potential applications in drug delivery.
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http://dx.doi.org/10.1002/anie.201900917DOI Listing
June 2019

Supramolecular Spheres Self-Assembled from Conical Dendrons Are Chiral.

J Am Chem Soc 2019 04 2;141(15):6162-6166. Epub 2019 Apr 2.

Roy & Diana Vagelos Laboratories, Department of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104-6323 , United States.

Frank-Kasper phases and liquid quasicrystals self-organize from supramolecular spheres of dendrimers, block copolymers, surfactants and other self-assembling molecules. These spheres are expected to be achiral due to their isotropic shape. Nevertheless, supramolecular spheres from short helical stacks of crown-like dendrimers self-organize a Pm3̅ n cubic (Frank-Kasper A15) phase which exhibits chirality on the macroscopic scale. However, the chirality of classic isotropic supramolecular micellar-like spheres, generated from conical dendrons, is unknown. Here we report a library of second and third generation biphenylpropyl dendrons with chiral groups at their apex that produces single-handed chiral supramolecular spheres. Up to 480 conical dendrons self-assemble to form micellar-like spheres, with a molar mass of up to 1.1 × 10 g/mol, that self-organize into a Pm3̅ n phase with chirality detectable on the macroscopic scale. This demonstration of chirality in micellar-like spheres of a Frank-Kasper phase raises the fundamental question whether micellar-like spheres forming 3D phases generated from other soft matter such as block copolymers, surfactants, and other molecules are chiral.
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http://dx.doi.org/10.1021/jacs.9b02206DOI Listing
April 2019

Fuel-Free Micro-/Nanomotors as Intelligent Therapeutic Agents.

Chem Asian J 2019 Jul 3;14(14):2325-2335. Epub 2019 Apr 3.

School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510275, China.

There are many efficient biological motors in Nature that perform complex functions by converting chemical energy into mechanical motion. Inspired by this, the development of their synthetic counterparts has aroused tremendous research interest in the past decade. Among these man-made motor systems, the fuel-free (or light, magnet, ultrasound, or electric field driven) motors are advantageous in terms of controllability, lifespan, and biocompatibility concerning bioapplications, when compared with their chemically powered counterparts. Therefore, this review will highlight the latest biomedical applications in the versatile field of externally propelled micro-/nanomotors, as well as elucidating their driving mechanisms. A perspective into the future of the micro-/nanomotors field and a discussion of the challenges we need to face along the road towards practical clinical translation of external-field-propelled micro-/nanomotors will be provided.
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http://dx.doi.org/10.1002/asia.201900129DOI Listing
July 2019

Active, Autonomous, and Adaptive Polymeric Particles for Biomedical Applications.

Biomacromolecules 2019 03 7;20(3):1135-1145. Epub 2019 Jan 7.

Institute of Molecules and Materials, Radboud University , Heyendaalseweg 135 , 6525 AJ Nijmegen , The Netherlands.

Nature's motors are complex and efficient systems, which are able to respond to many different stimuli present in the cell. Nanomotors for biomedical applications are designed to mimic nature's complexity; however, they usually lack biocompatibility and the ability to adapt to their environment. Polymeric vesicles can overcome these problems due to the soft and flexible nature of polymers. Herein we will highlight the recent progress and the crucial steps needed to fabricate active and adaptive motor systems for their use in biomedical applications and our approach to reach this goal. This includes the formation of active, asymmetric vesicles and the incorporation of a catalyst, together with their potential in biological applications and the challenges still to overcome.
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http://dx.doi.org/10.1021/acs.biomac.8b01673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415150PMC
March 2019

Poly(ionic liquid)s Based Brush Type Nanomotor.

Micromachines (Basel) 2018 Jul 23;9(7). Epub 2018 Jul 23.

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

A brush type nanomotor was fabricated via assembly assistant polymerization of poly(ionic liquid) and surface grafting polymerization. The method for large-scale fabrication of brush nanomotors with soft surfaces is described. These soft locomotive particles are based on core-shell brush nanoparticles assembled from poly(ionic liquid) as core and thermoresponsive PNIPAM as brush shells on which platinum nanoparticle (PtNP) were grown in situ. The particles show non-Brownian motion in H₂O₂ solution.
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http://dx.doi.org/10.3390/mi9070364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082249PMC
July 2018

Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes.

Biomacromolecules 2019 02 7;20(2):712-727. Epub 2018 Nov 7.

Roy & Diana Vagelos Laboratories, Department of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104-6323 , United States.

Natural, including plant, and synthetic phenolic acids are employed as building blocks for the synthesis of constitutional isomeric libraries of self-assembling dendrons and dendrimers that are the simplest examples of programmed synthetic macromolecules. Amphiphilic Janus dendrimers are synthesized from a diversity of building blocks including natural phenolic acids. They self-assemble in water or buffer into vesicular dendrimersomes employed as biological membrane mimics, hybrid and synthetic cells. These dendrimersomes are predominantly uni- or multilamellar vesicles with size and polydispersity that is predicted by their primary structure. However, in numerous cases, unilamellar dendrimersomes completely free of multilamellar assemblies are desirable. Here, we report the synthesis and structural analysis of a library containing 13 amphiphilic Janus dendrimers containing linear and branched alkyl chains on their hydrophobic part. They were prepared by an optimized iterative modular synthesis starting from natural phenolic acids. Monodisperse dendrimersomes were prepared by injection and giant polydisperse by hydration. Both were structurally characterized to select the molecular design principles that provide unilamellar dendrimersomes in higher yields and shorter reaction times than under previously used reaction conditions. These dendrimersomes are expected to provide important tools for synthetic cell biology, encapsulation, and delivery.
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http://dx.doi.org/10.1021/acs.biomac.8b01405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571140PMC
February 2019

Clinical Evidence for Use of a Noninvasive Biosensor for Tear Glucose as an Alternative to Painful Finger-Prick for Diabetes Management Utilizing a Biopolymer Coating.

Biomacromolecules 2018 11 25;19(11):4504-4511. Epub 2018 Oct 25.

NovioSense B.V., NovioTech Campus, Transistorweg 5 , Nijmegen 6534 AT , The Netherlands.

Diabetes is a metabolic condition that is exponentially increasing worldwide. Current monitoring methods for diabetes are invasive, painful, and expensive. Herein, we present the first multipatient clinical trial that demonstrates clearly that tear fluid may be a valuable marker for systemic glucose measurements. The NovioSense Glucose Sensor, worn under the lower eye lid (inferior conjunctival fornix), is reported to continuously measure glucose levels in the basal tear fluid with good correlation to blood glucose values, showing clear clinical feasibility in both animals and humans. Furthermore, the polysaccharide coated device previously reported by our laboratory when worn, does not induce pain or irritation. In a phase II clinical trial, six patients with type 1 Diabetes Mellitus were enrolled and the capability of the device to measure glucose in the tear fluid was evaluated. The NovioSense Glucose Sensor gives a stable signal and the results correlate well to blood glucose values obtained from finger-prick measurements determined by consensus error grid analysis.
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http://dx.doi.org/10.1021/acs.biomac.8b01429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234487PMC
November 2018

Hierarchical Self-Organization of Chiral Columns from Chiral Supramolecular Spheres.

J Am Chem Soc 2018 10 4;140(41):13478-13487. Epub 2018 Oct 4.

Roy & Diana Vagelos Laboratories, Department of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104-6323 , United States.

The supramolecular column is an archetypal architecture in the field of periodic liquid crystalline and crystalline arrays. Columns are generated via self-assembly, coassembly, and polymerization of monomers containing molecules shaped as discs, tapered, twin- and Janus-tapered, crowns, hat-shaped crowns, and fragments thereof. These supramolecular columns can be helical and therefore exhibit chirality. In contrast, spheres represent a fundamentally distinct architecture, generated from conical and crown-like molecules, which self-organize into body-centered cubic, Pm3̅ n cubic (also known as Frank-Kasper A15), and tetragonal (also known as Frank-Kasper σ) phases. Supramolecular spherical aggregates are not known to further assemble into a columnar architecture, except as an intermediate state between a columnar periodic array and a cubic phase. In the present work, a chiral dendronized cyclotetraveratrylene (CTTV) derivative is demonstrated to self-organize into a supramolecular column unexpectedly constructed from supramolecular spheres, with no subsequent transition to a cubic phase. Structural and retrostructural analysis using a combination of differential scanning calorimetry, X-ray diffraction (XRD), molecular modeling, and simulation of XRD patterns reveals that this CTTV derivative, which is functionalized with eight chiral first-generation minidendrons, self-organizes via a column-from-spheres model. The transition from column to column-from-spheres was monitored by circular dichroism spectroscopy, which demonstrated that both the supramolecular column and supramolecular spheres are chiral. This column-from-spheres model, which unites two fundamentally distinct self-assembled architectures, provides a new mechanism to self-organize supramolecular columnar architectures.
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http://dx.doi.org/10.1021/jacs.8b09174DOI Listing
October 2018

A Supramolecular Approach to Nanoscale Motion: Polymersome-Based Self-Propelled Nanomotors.

Acc Chem Res 2018 09 4;51(9):1891-1900. Epub 2018 Sep 4.

Institute of Molecules and Materials , Radboud University , Heyendaalseweg 135 , 6525 AJ Nijmegen , The Netherlands.

Autonomous micro- and nanoscale systems have revolutionized the way scientists look into the future, opening up new frontiers to approach and solve problems via a more bioinspired route. However, to achieve systems with higher complexity, superior output control, and multifunctionality, an in-depth study of the different factors that affect micro- and nanomotor behavior is crucial. From a fundamental perspective, the mechanical response of micro- and nanomotors still requires further study in order to have a better understanding of how exactly these systems operate and the different mechanisms of motion that can be combined into one system to achieve an optimal response. From a design engineering point of view, compatibility, degradability, specificity, sensitivity, responsiveness, and efficiency of the active systems fabricated to this point have to be addressed, with respect to the potential of these devices for biomedical applications. Nonetheless, optimizing the system with regards to all these areas is a challenging task with the micro- and nanomotors studied to date, as most of them consist of materials or designs that are unfavorable for further chemical or physical manipulation. As this new field of self-powered systems moves forward, the need for motor prototypes with different sizes, shapes, chemical functionalities, and architectures becomes increasingly important and will define not only the way active systems are powered, but also the methods for motor fabrication. Bottom-up supramolecular approaches have recently emerged as great candidates for the development of active structures that allow for chemical or physical functionalization, shape transformation, and compartmentalization, in a structure that provides a soft interface to improve molecular recognition and cell uptake. Our group pioneers the use of supramolecular structures as catalytically propelled systems via the fabrication of stomatocyte or tubular-shaped motors capable of displaying active motion in a substrate concentration-dependent fashion. This behavior demonstrates the potential of bottom-up assemblies for powering motion at the micro- or nanoscale, with a system that can be readily tuned and controlled at the molecular level. In this Account, we highlight the steps we have taken in order to understand and optimize the design of catalytically powered polymersome-based motors. Our research has been focused on addressing the importance of motor architecture, motion activation, direction control, and biological integration. While our work supports the feasibility of supramolecular structures for the design of active systems, we strongly believe that we are still in the initial stages of unveiling the full potential of supramolecular chemistry in the micro- and nanomotor field. We look forward to using this approach for the development of multifunctional and stimuli-responsive systems in the near future.
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http://dx.doi.org/10.1021/acs.accounts.8b00199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150652PMC
September 2018

High-Throughput Design of Biocompatible Enzyme-Based Hydrogel Microparticles with Autonomous Movement.

Angew Chem Int Ed Engl 2018 07 5;57(31):9814-9817. Epub 2018 Jul 5.

Department Systems Chemistry, Institution Radboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.

Micro- and nanomotors and their use for biomedical applications have recently received increased attention. However, most designs use top-down methods to construct inorganic motors, which are labour-intensive and not suitable for biomedical use. Herein, we report a high-throughput design of an asymmetric hydrogel microparticle with autonomous movement by using a microfluidic chip to generate asymmetric, aqueous, two-phase-separating droplets consisting of poly(ethylene glycol) diacrylate (PEGDA) and dextran, with the biocatalyst placed in the PEGDA phase. The motor is propelled by enzyme-mediated decomposition of fuel. The speed of the motors is influenced by the roughness of the PEGDA surface after diffusion of dextran and was tuned by using higher molecular weight dextran. This roughness allows for easier pinning of oxygen bubbles and thus higher speeds of the motors. Pinning of bubbles occurs repeatedly at the same location, thereby resulting in constant circular or linear motion.
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http://dx.doi.org/10.1002/anie.201805661DOI Listing
July 2018

Stomatocyte in Stomatocyte: A New Shape of Polymersome Induced via Chemical-Addition Methodology.

Nano Lett 2018 03 23;18(3):2081-2085. Epub 2018 Feb 23.

Radboud University Nijmegen, Institute for Molecules and Materials , Heyendaalseweg 135 , 6525 AJ Nijmegen , The Netherlands.

Accurate control of the shape transformation of polymersome is an important and interesting challenge that spans across disciplines such as nanomedicine and nanomachine. Here, we report a fast and facile methodology of shape manipulation of polymersome via out-of-equilibrium polymer self-assembly and shape change by chemical addition of additives. Due to its increased permeability, hydrophilicity, and fusogenic properties, poly(ethylene oxide) was selected as the additive for bringing the system out of equilibrium via fast addition into the polymersome organic solution. A new shape, stomatocyte-in-stomatocyte (sto-in-sto), is obtained for the first time. Moreover, fast shape transformation within less than 1 min to other relevant shapes such as stomatocyte and large compound vesicles was also obtained and accurately controlled in a uniform dispersion. This methodology is demonstrated as a general strategy with which to push the assembly further out of equilibrium to generate unusual nanostructures in a controllable and fast manner.
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http://dx.doi.org/10.1021/acs.nanolett.8b00187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997403PMC
March 2018

Motion Manipulation of Micro- and Nanomotors.

Adv Mater 2017 Oct 25;29(39). Epub 2017 Aug 25.

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands.

Inspired by the self-migration of microorganisms in nature, artificial micro- and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. These self-propelled micro- and nanomotors, designed either by top-down or bottom-up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro-/nanosurgery. For these various applications, especially biomedical applications, regulating on-demand the motion of micro- and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro- and nanomotors by different approaches.
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http://dx.doi.org/10.1002/adma.201701970DOI Listing
October 2017