Biological Effects Of Carbon Nanotubes:Drug Transport And Regulation Of Dipole Signal

Due to their unique structures and excellent physicochemical properties,carbon nanotubes(CNTs)show significant biological effects when they come into contact with organisms.Especially in terms of drug transport and dipole signal regulation,they are particularly outstanding and become a research hotspot,which are exactly the two aspects that this dissertation focuses on.First,CNTs show great potential in drug transport due to their considerable specific surface area,aspect ratio and internal hollow structure.However,existing studies have failed to fully reveal the detailed dynamic process and underlying mechanisms of drug transport,including the encapsulation of drug molecules in CNTs,the process of drug-CNT complex penetration in the cell membrane,and the release of drug molecules in the cell membrane.These biological phenomena and their mechanisms at the molecular level are unclear.Thus,this dissertation uses pregabalin(PRE)as a small drug molecule,a single-walled carbon nanotube(SWCNT)as the transport channel,and a lipid bilayer as the cell membrane model.In this dissertation,molecular dynamics simulation is used to investigate the penetration of pregabalin in lipid bilayer,the effect of concentration on the distribution of drug molecules in the cell membrane,the encapsulation and stability of drug molecules in the optimal CNT,the permeation of PRE-CNT complex in lipid bilayer and the release of drug molecules from CNT into the membrane.This dissertation explores the biological effect of drug transport,hoping to guide the way to the targeted drug therapy,and also hoping that CNTs,as carriers of molecular transport,can provide theoretical guidance in the areas of drug and gene transport,biosensors,and nanomedical diagnosis and treatment.Second,nanometer-sized CNTs play an important role in the regulation of dipole signals.This outstanding biological effect makes CNTs exhibit great potential in this field.Studies have shown that water molecules confined in the SWCNT with suitable diameter can form a single-file water chain.The orientation of the water chain can be regulated by the charge,and change with coordinated orientation.The charge signal is converted into the dipole signal of water in the CNTs.However,in the existing studies,the factors that can influence the flipping of water dipoles confined in the CNTs are not clear.Therefore,three aspects,namely,temperature,electric field,and charge are considered to investigate factors that can manipulate the flipping of water dipoles in the SWCNTs,and then provide technical solutions for the treatment of thermal noise using molecular dynamics simulation method.We hope that this dissertation can provide further theoretical guidance for CNTs as signal processing nanodevices.The main results and conclusions of this dissertation are as follows:1.In the encapsulating simulation of the early stage of drug transport,it is found that among the three different types of(6,6),(7,7)and(8,8)CNTs,the free energy of the drug molecule in(7,7)CNT is the lowest,about-72 k J/mol,much lower than that in aqueous solutions,resulting in drug molecules spontaneously entering the CNT from the aqueous solution and staying there steadily.Finally,they form the complex structure.This also shows that(7,7)CNTs are suitable as the best type of CNTs for encapsulating drug molecules.Furthermore,we find that the PRE-CNT complex can readily enter the lipid bilayer because of the hydrophobic interactions between CNT and lipid tails.Compared with the higher energy barrier(17.3 k J/mol)of drug molecules at the center of the lipid bilayer,the CNT has the lowest free energy(approximately-100 k J/mol)at the center of the membrane,indicating that the PRE-CNT complex can reduce the energy barrier entering the lipid bilayer and pass through the membrane center.2.In the later release simulation,it is found that the drug molecules release one by one from CNT into the lipid membrane,which is driven mainly by the electrostatic interactions between lipid headgroups and pregabalin polar groups.And the orientation of pregabalin at CNT ends with polar groups outward is beneficial to release.At the same time,compared with the case where one drug molecule cannot be released in the(7,7)CNTs with a length of 2.4 nm,the drug molecules in the(7,7)CNTs with a length of 1.6 nm can be completely released.It shows that shorter CNTs can improve the release rate of drug molecules.CNTs exhibit good application prospects in the field of drug transport.3.In the study of dipole signal regulation,it is found that as the temperature rises,the flipping frequency of water dipoles in the CNT increases because of the irregular thermal motion.This flipping of water dipoles driven by thermal motion can be controlled by the applied electric field and charge.When uniform electric fields are applied,the orientations of water dipoles in the CNT are in line with the direction of electric field,and change with the direction of electric field.Furthermore,when the uniform electric field strength is larger than 0.1 V/nm,the flipping of water dipoles originated from thermal motion in the CNT is well inhibited.Similar with the effects of uniform electric fields,the applied charge can also regulate the flipping frequency of the dipole signal of the water molecule.And the orientations of water dipoles change with the polarity of the charge.When the critical charge value is 1.0 e,the flipping of water dipoles is completely controlled.The thermal noise of the flipping of water dipoles in the CNT is well suppressed by the applied electric field or charge.