Biomimetic Design Of Self-propelled Synthetic Micro/nanomotors And Their Biomedical Applications

Artificial micro/nanomotors are micro/nanoscale devices or equipments capable of converting chemical energy or other energy into mechanical energy or movement to achieve self-propulsion. Inspired by the natural nanoscale linear biomotors, substantial efforts towards the design and fabrication of self-propelled synthetic motors at the micro- and nanoscale. For example, the catalytically chemical-powered micro/nanomotors are capable to achieve self-propulsion by the decomposition of hydrogen peroxide as fuel. However, most of these synthetic motors still have some inherent limitations, including complex preparation technology, d ifficulty of surface modification, and poor biocompatibility or biodegradability.In this thesis we demonstrate the construction of self-propelled biomimetic micro/nanomotor system based on controllable assembly and biomimetic design. We have firstly report an autonomous polymer multilayer nanomotors through Layer-by-Layer technique. The polymer multilayer nanomotors are constructed with natural macromolecules, their speed can be tuned through changing the fuel concentration, and the motion direction can be controlled by employing an external magnetic field. The advantages of the polymer multilayer tubular nanomotor in this part lie on:(1) the composition of biocompatible and biodegradable natural polymers;(2) these as-assembled nanomotors are able to be served as both autonomous motor and smart cargo. Based on the polymer multilayer nanomotor, we further describe a biodegradable, protein-based, autonomous bovine serum albumin/poly-L-lysine(PLL/BSA) multilayer motor as a smart vehicle for anticancer drug d elivery to cancer cells and near-infrared light controlled release. The motors were constructed by a template assisted layer-by-layer assembly of the bovine serum albumin/poly-L-lysine(BSA/PLL) multilayers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These motors can rapidly deliver the doxorubicin to the targeted cancer cell through a combination of biocatalytic bubble propulsion and magnetic guidance. The introduction of hydrogel into the nanomotor allows for the efficient loading of drug. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for release of the loaded doxorubicin and efficient killing of the cancer cells.In order to modulate the on-demand motion of catalytic polymer-based motor, we demonstrate a near-infrared light-triggered “on/off” motion of polymer multilayer motor which was fabricated by the template-assisted layer-by-layer assembly and subsequently deposition of platinum nanoparticles inside and a thin gold shell outside. Then a mixed monolayer of a tumor-targeted peptide and an antifouling poly(ethylene glycol) was functionalized on the gold shell. The micromotor remains motionless at the critical peroxide concentration(0.1%, v/v); however, NIR illumination on the motor leads to a photothermal effect and thus rapidly triggers the motion of the catalytic motor. The targeted recognition ability and subsequently killing of cancer cells by the photothermal effect under the higher power of a NIR laser were illustrated. The novelty in the chart lies on the demonstration of a approach to manipulate the near infrared light-triggered “on/off” motion of the gold nanoshell coated nanomotor under critical concentration of fuel.To avoid the toxicity of the fuel of hydrogen peroxide in the biomedi cal application of the nanomotors, gold nanoshell functionalized polymeric multilayer motor is demonstrated for non-fuel near-infrared light(NIR) triggered highly effective propulsion in various aqueous media to eliminate the acquirement of chemical fuel. The hybrid motor is fabricated by template-assisted polymer layer-by-layer(Lb L) assembly followed by the deposition of gold shell inside. The NIR-propelled motor moves rapidly with a robust directionality along the elongated axis of motor. The speed of motor in water goes up to 160 μm/s(over 13 body length/s). A theoretical model on the propulsion mechanism of the nanomotor is developed based on the photothermal effect of motor under NIR exposure. The NIR illumination could be used for the on-demand and reversible “on/off” motion control of the motor. This NIR-driven motor is able to move efficiently in various biofluids and subsequently induce the apoptosis of cancer cells under the high power of NIR irradiation. The novelty of near infrared light-propelled nanomotor is the movement of motor with the absence of chemical fuel, the theoretical simulation results illustrate the self- thermophoresis is the drive force of the near infrared light-propelled motor.To improve the functionalization of the micro/nanomotor, a red blood cell membrane-coated gold nanowire with ultrasound-powered movement was demonstrated as a new generation of red blood cell-camouflage nanomotor. The cell-camouflage nanomotors were constructed by the fusion of biocompatible gold nanowire motors and red blood cell nanovesicles. The biomimetic red blood cell-camouflaged nanomotor possess a high coverage of red blood cell vesicles, which remain totally functional due to its extracellular functional portion is exclusively oriented on the surfaces of nanomotors. The biomimetic red blood cell-camouflaged nanomotor display efficient and controllable acoustical propulsion, as well as powerful propulsion in the undiluted whole blood. The red blood cell vesicles on the nanomotors remain highly stable during the propulsion process, conferring thus the ability to absorb membrane-damaging toxins and allowing the nanomotors to be used as efficient toxin decoys. The efficient propulsion of the nanomotors under an ultrasound field results in accelerated neutralization of the membrane-damaging toxins. The thesis also demonstrates the turning natural red blood cells into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into red blood cells, where their asymmetric distribution within cells results in a net magnetization, enabling magnetic guidance under acoustic propulsion. The red blood cell motors display guided and prolonged propulsion in various biological fluids, including blood. Since the red blood cell motors preserve the biological features of natural red blood cells, these motors possess a wide range of antigenic, transport, and mech anical properties that common motors cannot achieve and hold considerable promise for a number of practical biomedical uses. The main novelty of this chart is the constr uction of cell membrane-coated ultrasound-propelled motors, these motors are able to perform in diverse biofludics, and shield to the uptake of immune cells for detoxification.To sum up, we demonstrate a serious of biomimetic micro/nanomotors with biocompatible and biodegradable capability based on controllable assembly and biomimetic design. Compared with ordinary synthetic micro/nanomotor, the biomimtic micro/nanomotor are constructed by natural macromolecule, and the near infrared light-triggered on demand motion of nanomotors are also achieved. To avoid the toxicity of chemical fuel to the living organisms, we present fuel-free near infrared light-propelled and ultrasound-propelled nanomotors. We reported the fusion of cell membrane and synthetic nanomotor as cell membrane-camouflage biomimetic nanomotor, and we further demonstrate the red blood cell-based micromotor as a new biomimetic generation of micro/nanomotor.