ATP synthase: the right size base model for nanomotors in nanomedicine.
ABSTRACT: Nanomedicine results from nanotechnology where molecular scale minute precise nanomotors can be used to treat disease conditions. Many such biological nanomotors are found and operate in living systems which could be used for therapeutic purposes. The question is how to build nanomachines that are compatible with living systems and can safely operate inside the body? Here we propose that it is of paramount importance to have a workable base model for the development of nanomotors in nanomedicine usage. The base model must placate not only the basic requirements of size, number, and speed but also must have the provisions of molecular modulations. Universal occurrence and catalytic site molecular modulation capabilities are of vital importance for being a perfect base model. In this review we will provide a detailed discussion on ATP synthase as one of the most suitable base models in the development of nanomotors. We will also describe how the capabilities of molecular modulation can improve catalytic and motor function of the enzyme to generate a catalytically improved and controllable ATP synthase which in turn will help in building a superior nanomotor. For comparison, several other biological nanomotors will be described as well as their applications for nanotechnology.
Project description:The development of artificial nanomotor systems that are stimuli-responsive is still posing many challenges. Herein, we demonstrate the self-assembly of a redox-responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli-responsive nanomotors are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox-responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.
Project description:Synthetic nanomotors are appealing delivery vehicles for the dynamic transport of functional cargo. Their translation toward biological applications is limited owing to the use of non-degradable components. Furthermore, size has been an impediment owing to the importance of achieving nanoscale (ca. 100?nm) dimensions, as opposed to microscale examples that are prevalent. Herein, we present a hybrid nanomotor that can be activated by near-infrared (NIR)-irradiation for the triggered delivery of internal cargo and facilitated transport of external agents to the cell. Utilizing biodegradable poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PDLLA) block copolymers, with the two blocks connected via a pH sensitive imine bond, we generate nanoscopic polymersomes that are then modified with a hemispherical gold nanocoat. This Janus morphology allows such hybrid polymersomes to undergoing photothermal motility in response to thermal gradients generated by plasmonic absorbance of NIR irradiation, with velocities ranging up to 6.2±1.10??m?s-1 . These polymersome nanomotors (PNMs) are capable of traversing cellular membranes allowing intracellular delivery of molecular and macromolecular cargo.
Project description:Current chemical-fuel-driven nanomotors are driven by gas (e.g. H2, O2, NH3) which only provides motion ability, and can produce waste (e.g. Mg(OH)2, Pt). Here, inspired by endogenous biochemical reactions in the human body involving conversion of amino acid L-arginine to nitric oxide (NO) by NO synthase (NOS) or reactive oxygen species (ROS), we report on a nanomotor made of hyperbranched polyamide/L-arginine (HLA). The nanomotor utilizes L-arginine as fuel for the production of NO both as driving force and to provide beneficial effects, including promoting endothelialisation and anticancer effects, along with other beneficial by-products. In addition, the HLA nanomotors are fluorescent and can be used to monitor the movement of nanomotors in vivo in the future. This work presents a zero-waste, self-destroyed and self-imaging nanomotor with potential biological application for the treatment of various diseases in different tissues including blood vessels and tumours.
Project description:A motion-based chemical sensing involving fuel-driven nanomotors is demonstrated. The new protocol relies on the use of an optical microscope for tracking changes in the speed of nanowire motors in the presence of the target analyte. Selective and sensitive measurements of trace silver ions are illustrated based on the dramatic and specific acceleration of bimetal nanowire motors in the presence of silver. Such nanomotor-based measurements would lead to a wide range of novel and powerful chemical and biological sensing protocols.
Project description:It is of great interest and big challenge to control the collective behaviors of nanomotors to mimic the aggregation/separation behavior of biological systems. Here, a light-acoustic combined method is proposed to control the aggregation/separation of artificial nanomotors. It is shown that nanomotors aggregate at the pressure node in acoustic field and afterward present a collective "firework" separation behavior induced by light irradiation. The collective behavior is found to be applicable for metallic materials and polymers even different light wavelengths are used. Physical insights on the collective firework behavior resulting from the change of acoustic streaming caused by optical force are provided. It is found that diffusion velocity and diffusion region of cluster can be controlled by adjusting light intensity and acoustic excitation voltage, and irradiation direction, respectively. This harmless, controllable, and widely applicable method provides new possibilities for groups of nanomachines, drug release, and cargo transport in nanomedicine and nanosensors.
Project description:Both DNA and RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures. A pioneering concept proposed by Ned Seeman 30 years ago has led to an explosion of knowledge in DNA nanotechnology. RNA can be manipulated with simplicity characteristic of DNA, while possessing noncanonical base-pairing, versatile function, and catalytic activity similar to proteins. However, standing in awe of the sensitivity of RNA to RNase degradation has made many scientists flinch away from RNA nanotechnology. Here we report the construction of stable RNA nanoparticles resistant to RNase digestion. The 2'-F (2'-fluoro) RNA retained its property for correct folding in dimer formation, appropriate structure in procapsid binding, and biological activity in gearing the phi29 nanomotor to package viral DNA and producing infectious viral particles. Our results demonstrate that it is practical to produce RNase-resistant, biologically active, and stable RNA for application in nanotechnology.
Project description:Plasmonic near-field coupling can induce the enhancement of photoresponsive processes by metal nanoparticles. Advances in nanostructured metal synthesis and theoretical modeling have kept surface plasmons in the spotlight. Previous efforts have resulted in significant intensity enhancement of organic dyes and quantum dots and increased absorption efficiency of optical materials used in solar cells. Here, we report that silver nanostructures can enhance the conversion efficiency of an interesting type of photosensitive DNA nanomotor through coupling with incorporated azobenzene moieties. Spectral overlap between the azobenzene absorption band and plasmonic resonances of silver nanowires increases light absorption of photon-sensitive DNA motor molecules, leading to 85% close-open conversion efficiency. The experimental results are consistent with our theoretical calculations of the electric field distribution. This enhanced conversion of DNA nanomotors holds promise for the development of new types of molecular nanodevices for light manipulative processes and solar energy harvesting.
Project description:We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(?-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 ?m/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.
Project description:Motility in living systems is due to an array of complex molecular nanomotors that are essential for the function and survival of cells. These protein nanomotors operate not only despite of but also because of stochastic forces. Artificial means of realizing motility rely on local concentration or temperature gradients that are established across a particle, resulting in slip velocities at the particle surface and thus motion of the particle relative to the fluid. However, it remains unclear if these artificial motors can function at the smallest of scales, where Brownian motion dominates and no actively propelled living organisms can be found. Recently, the first reports have appeared suggesting that the swimming mechanisms of artificial structures may also apply to enzymes that are catalytically active. Here we report a scheme to realize artificial Janus nanoparticles (JNPs) with an overall size that is comparable to that of some enzymes ?30 nm. Our JNPs can catalyze the decomposition of hydrogen peroxide to water and oxygen and thus actively move by self-electrophoresis. Geometric anisotropy of the Pt-Au Janus nanoparticles permits the simultaneous observation of their translational and rotational motion by dynamic light scattering. While their dynamics is strongly influenced by Brownian rotation, the artificial Janus nanomotors show bursts of linear ballistic motion resulting in enhanced diffusion.
Project description: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 <i>in vivo</i> 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 H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub> in the presence of only 2 mM H<sub>2</sub>O<sub>2</sub>, and the velocity of motors correlated to the O<sub>2</sub> 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.