Intrinsic enzymatic properties modulate the self-propulsion of micromotors

Arqué, Xavier; Romero‐Rivera, Adrian; Feixas, Ferran; Patiño, Tania; Osuna, Sílvia; Sánchez, Samuel

doi:10.1038/s41467-019-10726-8

Cited by 137 publications

(151 citation statements)

References 63 publications

(83 reference statements)

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…The self-propulsion of urease-modified micro-/nanomotors (4,(52)(53)(54) is caused the asymmetric release of ionic species from the particles to the solution (55) which stems from the catalytic decomposition of urea into carbon dioxide and ammonia. Despite the recent advances in the field, enzyme nanomotors have been only studied from single particle to a few particles case, being their collective swarming behaviour not investigated to date.…”

Section: Introductionmentioning

confidence: 99%

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

Hortelão

Simó

Guix

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Enzyme powered nanomotors hold great potential for biomedical applications, as they show improved diffusion and navigation within biological environments using endogenous fuels. Yet, understanding their collective behavior and tracking them in vivo is paramount for their clinical translation. Here, we report on the in vitro and in vivo study of swarms of selfpropelled enzyme-nanomotors and the effect of collective behavior on the nanomotors distribution within the bladder. For that purpose, mesoporous silica nanomotors were functionalized with urease enzymes and gold nanoparticles. Two radiolabeling strategies, i.e. absorption of 124 I on gold nanoparticles and covalent attachment of an 18 F-labeled prosthetic group to urease, were assayed. In vitro experiments using optical microscopy and positron emission tomography (PET) showed enhanced fluid mixing and collective migration of nanomotors in phantoms containing complex paths. Biodistribution studies after intravenous administration in mice confirmed the biocompatibility of the nanomotors at the administered dose, the suitability of PET to quantitatively track nanomotors in vivo, and the convenience of the 18 F-labeling strategy. Furthermore, intravesical instillation of nanomotors within the bladder in the presence of urea resulted in a homogenous distribution after the entrance of fresh urine. Control experiments using BSA-coated nanoparticles or nanomotors in water resulted in sustained phase separation inside the bladder, demonstrating that the catalytic decomposition of urea can provide urease-nanomotors with active motion, convection and mixing capabilities in living reservoirs. This active collective dynamics, together with the medical imaging tracking, constitutes a key milestone and a step forward in the field of biomedical nanorobotics, paving the way towards their use in theranostic applications.to the use of endogenous fuels, which enables nanomotors' on-site activation and the design of fully biocompatible motor-fuel complexes. Moreover, the library of enzyme/substrate combinations permits the design of application-tailored enzymatic nanomotors, as is the case of urease-powered nanomotors for bladder cancer therapy. (4) Yet, the large number of nanoparticles required to treat tumors (18) demands for a better understanding, control and visualization of nanoparticle swarms to aid in the evaluation of motile nanomedicines and facilitate the eventual translation into clinics. Indeed, collective phenomena commonly observed in nature (active filaments,(19) bacteria quorum sensing,(20) cell migration,(21) swarms of fish, ants, and birds)(22) also occurs in micro-/nanomotors, which demonstrated collective migration,(23-26) assembly,(27-30) or aggregation/diffusion behaviors in vitro.(31-38) Ex vivo, swarms of magnetic micropropellers demonstrated longrange propulsion through porcine eyes to the retina, suggesting potential as active ocular delivery devices.(39, 40) In vivo, controlled swimming of micromotor swarms was shown in mouse peritoneal cavities,(41)...

show abstract

Section: Introductionmentioning

confidence: 99%

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

Hortelão

Simó

Guix

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…[20] In JBU, the residues comprising the mobile flap are 590-606 on α subunit part of the enzyme. [21] The molecular interactions of thiourea and the compounds 8e…”

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

New 1,2,3‐triazole–(thio)barbituric acid hybrids as urease inhibitors: Design, synthesis, in vitro urease inhibition, docking study, and molecular dynamic simulation

Asgari

Azizian

Montazer

et al. 2020

Archiv der Pharmazie

View full text Add to dashboard Cite

A new series of 1,2,3‐triazole–(thio)barbituric acid hybrids 8a–n was designed and synthesized on the basis of potent pharmacophores with urease inhibitory activity. Therefore, these compounds were evaluated against Helicobacter pylori urease. The obtained result demonstrated that all the synthesized compounds, 8a–n, were more potent than the standard urease inhibitor, hydroxyurea. Moreover, among them, compounds 8a, 8c–e, 8g,h, and 8k,l exhibited higher urease inhibitory activities than the other standard inhibitor used: thiourea. Docking studies were performed with the synthesized compounds. Furthermore, molecular dynamic simulation of the most potent compounds, 8e and 8l, showed that these compounds interacted with the conserved residues Cys592 and His593, which belong to the active site flap and are essential for enzymatic activity. These interactions have two consequences: (a) blocking the movement of a flap at the entrance of the active site channel and (b) stabilizing the closed active site flap conformation, which significantly reduces the catalytic activity of urease. Calculation of the physicochemical and topological properties of the synthesized compounds 8a–n predicted that all these compounds can be orally active. The ADME prediction of compounds 8a–n was also performed.

show abstract

“…In another study, [132] they not only successfully manipulated the motion direction of the motors by incorporating magnetic material within the Janus motor structure but also efficiently controlled their velocity by chemically inhibiting and reactivating the enzymatic activity. In addition, they made an in-depth research [133] on the possibility of utilizing the intrinsic enzymatic properties including turnover number and conformational dynamics to modulate the motility of the micromotors. Both the molecular dynamics simulations and experimental results revealed that among the four different enzymes they selected (urease, acetylcholinesterase, glucose oxidase, and aldolase), urease and acetylcholinesterase were capable to produce active motion and displayed the highest degree of flexibility near the active site due to their higher catalytic rates.…”

Section: Enzyme-powered Micro/nanomotorsmentioning

confidence: 99%

Recent Advances in Motion Control of Micro/Nanomotors

Yang

Zhong

et al. 2020

Advanced Intelligent Systems

View full text Add to dashboard Cite

Micro/nanomotors are able to convert energy in different forms into propulsion and movement with predesigned directions and velocities, enabling them to be self‐propelled carriers and vehicles for the delivery of active pharmaceutical ingredients and other biomedical cargos to the target sites such as tumors. However, the inadequate energy and noncontrollable moving directions remain the grand challenges for their promising applications. Recently, an increasing attention has been paid to these issues and numerous reported researches have focused to design and develop more efficient and precisely controllable micro/nanomotors with different methods. This review aims to summarize those studies and to introduce newly developed micro/nanomotors including synthetic micro/nanomotors and biohybrid motors, discussing the control mechanisms as well as advantages and limitations thereof. Conclusions and future perspectives are also provided in brief.

show abstract

Intrinsic enzymatic properties modulate the self-propulsion of micromotors

Cited by 137 publications

References 63 publications

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

New 1,2,3‐triazole–(thio)barbituric acid hybrids as urease inhibitors: Design, synthesis, in vitro urease inhibition, docking study, and molecular dynamic simulation

Recent Advances in Motion Control of Micro/Nanomotors

Contact Info

Product

Resources

About