1. Introduction

Since the 21st century, the concept of nanomedicine technology has been widely accepted1. Traditional drugs, especially cancer treatment drugs, often have poor water solubility, low bioavailability, and poor targeting, making it impossible to complete timely and effective drug treatment2. With the vigorous development of nanotechnology, the way of drug delivery has undergone earth-shaking changes. On the one hand, people have developed nano-micro tools to assist drug absorption through nanotechnology, such as polymer MNs, enhancing transdermal drug delivery efficiency by opening skin channels3. On the other hand, researchers have prepared a series of drug-loaded nanoparticles using nano chemical methods, which can wrap poorly water-soluble drugs inside the micelles, protected by the hydrophilic molecular fragments the outside of the micelles, thereby enhancing the drug’s water solubility4. Those nanoparticles can also contain environmentally responsive components to adjust molecular properties according to changes in the external environment, by which the smart release of drugs can be obtained5. From now on, individuals have designed a large number of smart nanoparticles, which can effectively improve the treatment efficiency of anticancer drugs such as doxorubicin6 and paclitaxel7. Many drug-loaded particles can carry more functional components, having excellent development potential in medical imaging and sensing. The optimization design of more sensitive, versatile, and higher drug-loading nanosystems and even nanorobots’ research and development have always been hot topics in this field8.
However, similar to other drug delivery systems, nanoparticle development also faces various challenges due to the diverse components and complex in vivo environment9. Hu et al. have used computer simulation to explore the influence of molecular structure on the self-assembly morphology of the drug carrier and summarized the formation mechanism of various self-assembly structures such as micelles, vesicles, and membranes10. Guo et al. have utilized molecular simulation technology to explore the drug release mechanism of pH-responsive micelles, assisting researchers in the optimization design of nanomaterials11. Qiu et al. have put forward a variety of measures such as “physical cross-linking” to prevent drugs from leaking from the vesicles through experimental means12. Granick and his coworkers have studied the law of nanoparticle diffusion in polymer solution, which is beneficial for in-depth discussion of the nanoparticle delivery kinetics in the body13. At present, employing experiments and theoretical simulations, breakthroughs have been made in multiple aspects, such as drug loading efficiency, drug release mechanism, and nanoparticle dynamics research. However, most nanoparticles need to enter the cell in order to accomplish the delivery14. In the meantime, cellular cytotoxicity, the adverse effects of nanoparticles and macromolecules on cells, is also essential15. Therefore, it is of great pivotal to study the interaction between nanoparticles and cell membranes. Despite plenty of research has been reported in the fields of analyzing the nanoparticle cytotoxicity and the cell membrane morphology study by means of experimental methods16, there are still many areas where experiments cannot provide more complete support, including the absorption process as well as the interaction mechanism study at the molecular level. Thus, theoretical simulation plays a critical role in this topic. Through computer simulation, people can visualize nanoparticles’ endocytosis process and study various influencing factors that affect the absorption efficiency by rich modelling methods, assisting researchers to project better nanoparticle designs that can improve internalization efficiency and avoid cell damage17.
In this review, we will systematically review nanoparticle-cell membrane interaction research through computer simulation in recent years. Computer simulation refers to applying computer software to make reasonable assumptions in the movement of electrons and atoms18. At present, a rich type of molecular simulation technology has been developed that can be applied to the research of different space-time physics backgrounds. Considering the multiple components and the corresponding unique time-space scales, this review will focus on the application of dissipative particle dynamics (DPD) simulations based on the concept of coarse-grained in this field and several works that relate to the MARTINI force field are also mentioned11. First, we will review the commonly used modelling methods of nanoparticles and cell membranes. Subsequently, we will focus on reviewing many influencing factors that affect the interaction between nanoparticles and cell membranes, such as particle size, shape, chemical properties, concentration, etc., and summarize significant adjustment to improve the internalization efficiency of nanoparticles and the corresponding mechanism studies (Figure. 1). We hope this article may help molecular simulation researchers quickly familiarize themselves with the development of this field and various views on different researchers’ mechanism research. At the end of the article, the author’s comments and prospects will be given.