Theoretical Study Of Low-Dimensional Nanomaterials For Biomedical Applications

From the glittering nano-particles of the Lycurgus color-changing cup in a Roman church in the fourth century AD,to the carbon nanotubes found in the forging magic Uzi steel in the seventeenth century,which revealed the secret to cutting yarn with the Damascus saber in the air,and then to the application of nanotechnology and artificial intelligence by the British scientist Peter Morgan,who was suffering from amyotrophic lateral sclerosis,to transform himself into the world’s first "cyborg",the application of nanomaterials throughout human history.With the progress of scientific and technological civilization,human beings have discovered that when the particle size is reduced to the magnitude of nano,its optical,thermal,electromagnetic and mechanical properties will show new characteristics compared to macroscopic bulk materials,and the expansion of their applications has also covered from traditional energy,information,environmental protection and aerospace and military fields to biomedical and other fields,nanomaterials have shown extremely broad development prospects.In recent decades,in the field of biomedicine,low-dimensional nanomaterials have achieved fruitful experimental results in frontiers such as biomimetics,disease diagnosis and drug delivery.However,the lack of clarity in the internal mechanisms of traditional trial-and-error experimental exploration has led to research dilemmas such as high costs and long development cycles,thus hindering the further clinical translation and utilization of biomedical materials.With the popularization of computer technology,computer simulation technology can provide theoretical insights into the fundamental mechanisms of various physicochemical properties and biological effects of materials at the molecular/atomic scale,build a cognitive bridge from microstructure to properties,and provide a forward-looking theoretical perspective for relevant experimental research,thus effectively improving the efficiency of biomedical materials development.Based on the above consideration,this paper mainly adopts molecular dynamics simulations,first principles calculation and quantum chemical calculation to conduct in-depth theoretical research on the medical potential of several lowdimensional materials in biomimetics,disease diagnosis and drug delivery.The main contents are as follows.1.Theoretical study of carbon ene-yne working for gas exchange membrane in artificial lungArtificial lung is a short-term medical device designed based on the principle of alveolar gas exchange in the biological lung and can be used as an auxiliary means for patients with acute viral pneumonia.As the main part of the artificial lung,polymethylpentene(PMP),the preferred materials for hollow fiber membrane responsible for gas exchange,has complex manufacturing process,high price,limited production capacity and short of supply.To address these challenges,we designed a theoretical model that mimics the working principle of hollow fiber membranes and investigated the O2/CO2 permeability and waterproof performance of three typical twodimensional carbon materials that have been synthesized(y-graphyne,graphdiyne and carbon ene-yne).According to our theoretical calculations,the relatively small pore size of γ-graphyne monolayer leads to a high penetration energy barrier of gas molecules,which makes it difficult to perform the task of gas exchange.Although graphdiyne with slightly larger pore size can show a certain O2 permeability under high differential pressure,when the pressure difference drops to 803 mmHg,graphdiyne has lost its oxygen permeability.It is difficult to achieve gas exchange under the experimental value(500 mmHg).When the carbon ene-yne with a pore size of 7.1 ? is used,carbon ene-yne shows extremely high O2/CO2 permeability and waterproof performance.At room temperature and experimental pressure difference,its permeability to O2 molecules is almost reached six times of PMP.Therefore,carbon ene-yne might be a promising candidate as O2/CO2 exchange membrane for medical applications.We hope that these simulation results will provide an effective nanoscale bionic strategy for the design and optimization of novel gas exchange membrane materials for artificial lungs in the biomimetic field.2.Theoretical study of nitrogen-doped tungsten disulfide as a sniffer for lung cancer biomarkersNanosensor-based artificial olfaction is a non-invasive and inexpensive method for the early diagnosis of lung cancer,and the development of breath sensors that can selectively detect lung cancer biomarkers is one of the most critical challenges.Using the main components of healthy human breath(i.e.N2,O2,CO2 and H2O)as reference terms,we evaluated the sensing performance of synthesized monolayer tungsten disulfide(WS2)/nitrogen-doped tungsten disulfide(N-WS2)to three typical lung cancer biomarker molecules(2,3-Dimethylhexane,Styrene and Toluene),and the adsorption behavior,recovery time and differences in response of WS2/N-WS2 monolayer to these expiratory components.The weak adsorption of biomarkers and the resulting very short recovery time at room temperature prevent monolayer WS2 from fulfilling its role as a lung cancer sniffer.Based on a gas sensing mechanism that strongly electronegative nitrogen dopant allows significant electron accumulation at its adsorption site,monolayer N-WS2 is more sensitive to biomarkers,showing a strong physical adsorption capacity and a detectable recovery time at room temperature.The monolayer N-WS2 has a significant difference in electrical conductivity response to the breath of healthy people and lung cancer patients and can be used as a direct signal for the determination of lung cancer biomarkers in exhaled breath,and the response level is much higher than that of some experimentally reported gold nanoparticle sensors.Furthermore,the adsorption system formed by the lung cancer biomarkers and N-WS2 was thermally stable at 298 K,and humidity had little effect on the sensing performance of the monolayer N-WS2.Thus,monolayer N-WS2 arrays could be a promising fundamental element of lung cancer biomarker sniffer for rapid and cost-effective preliminary lung cancer diagnosis.3.Theoretical study of cucurbit[n]uril loading a potential anticancer drug mono-squaramideCTMS,a mono-squaramide molecule that combines the ability of cell autophagy and apoptosis,is a lipophilic anticancer drug candidate.In order to overcome its poor water solubility and improve its utilisation,we have explored the possibility of using the water-soluble macrocyclic molecule cucurbit[n]uril(CB[n],n=6,7 and 8)as a CTMS carrier through theoretical calculations.The size effect of the host molecule on the binding mode,adsorption properties,electronic properties and intermolecular interactions of the host-guest complex in the gas/water phase were discussed in detail.The results show that the small portal size of the CB[6]and the steric effect between the benzene ring of the CTMS molecule and the glycoluril unit of CB[6]during the embedding process,leading to a less stable "semi-embedded" binding mode.The van der Waals interactions and the hydrogen bonding between the carbonyl oxygen of CB[6]and the amino hydrogen of CTMS(N-H…O)result in a large structural twist of the CTMS molecule.Therefore,CB[6]is not a suitable carrier for CTMS.The port size of CB[8]is too large,although the host-guest molecules exhibit a stable "fully embedded"binding mode,the weak intermolecular interactions lead to a large structural deformation of CB[8],which has a greater impact on the structural stability of the host molecules and is not conducive to CB[8]accomplishing its loading task.In contrast,CB[7]has a more suitable portal size(8.5 ?),which not only forms a stable "fully embedded" complex structure,but also maintains the original conformation of the host and guest molecules.The van der Waals interactions and hydrogen bonding(N-H…O)are key factors in stabilizing the structure of the complexes.Therefore,the size effect of cucurbit[n]uril is a key factor affecting its drug-carrying capacity,and CB[7]may be an ideal carrier for delivering CTMS in relative terms.This work may provide some theoretical basis and clues for the related research on cucurbit[n]uril-based drug delivery systems.In summary,this paper employs multi-scale computer simulation techniques,from rational simplified model design,to atomic-level dynamic description of the recognition process of low-dimensional nanomaterials and target molecules,to atomic-level mining of interfacial interactions,which can provide reliable theoretical support for the application of low-dimensional materials in the biomedical field.