Biological & Biomedical Sciences Research Paper: Cell membrane-coated nanotherapeutics for personalized cancer therapy

Cell Membrane-Coated Nanotherapeutics
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Abstract
The continued advancements in biomedical nanomedicine have provided better opportunities for clinicians to detect, treat, manage, and prevent human diseases. Experts have adopted a paradigm shift towards biomimetic design techniques to push the limits of nanoparticle functionality and performance. Inspired by nature, these strategies are aimed at creating next-generation nanoparticle platforms that can navigate and interact with the complex biological systems in the body in a more effective way. This paper provides a comprehensive overview of cell membrane coated nanotechnology. Data is obtained from analyzing previous works of different researchers who have directly leveraged biomaterials obtained from the cell membrane to design novel nanodiagnostics and nanotherapeutics. This technology presents innumerable benefits that make it capable of covering various approaches in medicine. Although it has not been fully translated to the clinic, researchers believe that nanocarriers with benefits in human health will be designed in the future.
Keywords: nanotechnology, biointerfacing, cell membrane, cancer treatment, macrophage
Part 1
Introduction to Cell Membrane-coated Nanotechnology & Cancer Therapy
Nanoparticle‐based therapeutic, detection and prevention modalities have a great potential for impacting the diagnosis and management of diseases. The availability of several nanomaterials has resulted in the increased popularity of rational design nanocarriers based on specific applications. Cell‐membrane‐coating nanotechnology is one of the popular emerging techniques. These upcoming technologies have the potential of advancing nanomedicine, contributing to the improvement of traditional modalities while facilitating the development of novel applications.
In many cases, synthetic functionalization strategies are effective in replicating distinct biological interactions. However, the continued research on nanomedicine has revealed that replicating the collective functions of biological systems via bottom-up fabrication techniques has become quite difficult. The primary reason for this is because these strategies platforms are actually multifactorial and incredibly complex. Additionally, the fact that they are foreign in nature makes it even more challenging. For this reason, researchers are turning to biomimicry as leverage in the design of more efficient nanoplatforms.
Nanotechnology has played a substantial role in medicine, facilitating the development of more reliable solutions for addressing some of the crucial needs in human health. The cell membrane is a key element in this technology, considering its role and properties. A cell is one of the vital units in biology, carrying a broad range of functions. These include its excellent ability to interact and interface with the surrounding environment. Rather than trying to replicate such functions through synthetic methods, researchers are currently leveraging cell membranes that are acquired naturally as a way of generating nanoparticles with improved bio-interfacing capabilities.
Initially, this technology was utilized in the design of cancer-related therapies. However, several other applications, such as the creation of immunological tolerance and treatment of resistant bacteria, are currently being explored. Today, the introduction of natural membrane substrates on nanoparticle surfaces has facilitated other applications besides nanomedicine.
Different types of cells are used as sources of membranes for coating nanoparticles. Each one of them can utilize its unique properties to offer specific functionalities to the nanoparticulate core. Cell membranes consist of a mixture of proteins, carbohydrates, and lipids. Transferring the outer layer of a cell directly onto a nanoparticle surface allows the membrane to be preserved together with all its contents. It also enables the resultant nanoparticle to acquire a majority of the properties revealed by the source cell (Fang, Kroll, Gao, Zhang, 2018).
These nanoplatforms are often semi-artificial, benefiting from their inherited properties that include self-identification, biointerfacing, as well as signal transduction. These enable them to escape biological barriers like opsonization, immune clearance, and vascular system negotiation. Imaging, detoxification, immunotherapies, drug delivery, and photo therapies are some of the applications that can benefit from this technique. The top-down technique is highly generalizable, facile, and capable of augmenting the safety and potency of existing nanocarriers. When effective formulations, a considerable amount of effort is put into research to ensure their efficiency (Fang, Kroll, Gao, Zhang, 2018).
Part 2
The Structure and Functions of the Cell Membrane
Cancer therapy

Cancer is one of the leading causes of death across the globe. Most modern treatments, such as radiotherapy or chemotherapy, involve resecting the core tumor. Though they have varying rates of success, these therapies present both long and short-term adverse effects. Over the last few years, researchers have been focusing on developing a more reliable cancer nanomedicine with precise tumor targeting, solid biointerfacing, and efficient tumor-targeting ability. Cell membrane nanotechnology has captured the attention of many individuals in the field of nanomedicine. The technology allows researchers to exploit different cell functions. They can transfer some of the properties and functions of the cell membrane to the nanoparticles without passing through the complicated chemical processes. To understand the function of the cell membrane, it is imperative that you be well-versed in its structure.
Cell membrane structure
Essentially, these membranes are thin layers of about five to ten nm. They safeguard the cell from the surrounding environment. Enclosed by this membrane are three types of biomolecules; carbohydrates, lipids, and proteins. Different cell types have varying protein and lipid compositions and are dependent on their cellular function.
By integrating the physical aspects of nanomaterials into the cell membrane's natural bio interfacing abilities, it can facilitate the development of new treatments with multimodal functionalities. These include the ability to deliver a payload effectively, differentiate the healthy cells from cancer cells, as well as minimize nonspecific toxicity.
Proteins can either be intrinsic or extrinsic, depending on their pathological roles and interaction behavior. They are responsible for regulating pathogenicity and late signal transduction as well as vesicle flow. Some proteins (Uniporters) also serve as channels and pumps, facilitating the transport of molecules across the cell. Carbohydrates are also conjugated as glycoproteins and glycolipids.
The role of lipids is to maintain the bi-layer structure of the cell, regulate cell signaling, control fluidity, and flexibility. Glycolipids, fatty acids, phospholipids, sterols, phosphoglycerides, and sphingolipids are the primary types of lipids essential for the formation of cell membranes. These lipids contain both hydrophobic and hydrophilic components. When mixed with water, three different aggregates are formed. On the other hand, biological membranes are bilayers because of their internal conditions.
The cell membrane has several interesting functions, some of which may be exploited in the development of cell membrane coated nanotechnology. It is semi-permeable and serves as a barrier between the interior part of the cell and the outside environment. This enables the cells to maintain their integrity and allows the selective movement of molecules in and out (Cooper & Hausman, 2000). Also, they enable molecular transport and limit the exchange of other molecules.
Some uniporters carry molecules down the concentration gradient. This is known as passive transport. Active transport involves the movement of molecules against the concentration or electrical gradient. Cell signaling entails the process of information reception and transmission through which the cells communicate for various biological processes (Cooper & Hausman, 2000). The proteins in the cell membrane can serve as receptors where certain molecules mediate and bind biological functions.
Natural and synthetic membrane vesicles
The cells produce intracellular...