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.