Nanodiscs are synthetic phospholipid particles with a distinct morphology and size that enhance their efficiency in drug delivery applications.1 First developed by Sligar et al. in the early 2000s, these model membrane systems measure around 10 nm in diameter with a thickness between 4.6 and 5.6 nm.2 Structurally, nanodiscs are similar to high-density lipoproteins.
In medical applications, nanotechnology advancements have positioned nanodiscs as valuable tools for diagnosing and treating various diseases. These disc-shaped particles can preserve membrane proteins in their functional state outside the cellular environment, making them valuable in biomedical applications.1
Nanodiscs stabilize fragile proteins, enhance drug delivery, and provide a structured bilayer surface, proving highly effective for studying cellular signaling complexes on membrane surfaces.1 Their versatility continues to support advancements in modern medicine.
Classification of Nanodiscs
Nanodiscs can be categorized based on the stabilizer used to maintain their structure.3
Membrane Scaffold Protein Nanodiscs
Membrane scaffold protein (MSP) nanodiscs use amphipathic membrane scaffold proteins as stabilizers. These scaffold proteins encircle a stable, discoidal phospholipid bilayer containing embedded transmembrane proteins, forming the nanodisc structure.
MSP is typically a truncated form of apolipoprotein A-I (apoA-I), a component of high-density lipoproteins. It wraps around a small segment of the phospholipid bilayer to create the disc-shaped nanodisc.3
MSP provides a hydrophobic surface for lipid tails and a hydrophilic outer surface, making nanodiscs highly soluble in water. During assembly, excess detergent is used and later removed with bio-beads, allowing membrane proteins to stay in solution without detergents.
These nanodiscs are well-suited for studying membrane proteins in both prokaryotic and eukaryotic systems, including key structures like transporters, ion channels, and G protein-coupled receptors (GPCRs).4
Saposin nanodiscs
The saposin protein family consists of four members, saposin A–D, each with a molecular weight of around 10 kDa. Saposin A is most commonly used for assembling saposin nanodiscs. Frauenfeld et al. (2016) demonstrated the use of saposin proteins as scaffolds to reconstitute various membrane proteins within a phospholipid environment.5
Saposin nanodiscs self-assemble from saposin proteins, phospholipids, and membrane proteins into a stable structure that is adaptable to various membrane protein sizes without requiring scaffold construction or lipid ratio adjustments.3 Although a recent development, they are widely applied in structure-based techniques like NMR and cryo-EM, providing distinct advantages for both methods.
For example, in a solution-based NMR study, three membrane proteins were successfully incorporated into saposin nanodiscs: bacterial outer membrane protein X (OmpX), sensory receptor rhodopsin II (pSRII), and the β1-adrenergic receptor (β1AR).6
Copolymer Nanodiscs
Copolymer nanodiscs extract membrane proteins directly from cell membranes, preserving their native state and endogenous phospholipids. Synthetic polymers encapsulate the proteins into nanosized discs, stabilizing a portion of the native membrane. These nanodiscs use the cell’s natural phospholipids, with the polymer acting as both solubilizer and stabilizer, removing the need for additional detergents.3
Synthetic copolymers like styrene-maleic acid (SMA), diisobutylene maleic acid (DIBMA), and polymethacrylate (PMA) are used to stabilize nanodiscs, maintaining the lipid bilayer in aqueous solutions. These non-protein polymers self-assemble into stable structures and offer higher purity than MSP nanodiscs. They are widely used in membrane protein research, drug delivery, and biosensor applications.3
SMA nanodiscs have been successfully employed to purify and study integral membrane proteins from bacterial and eukaryotic systems. Once reconstituted into SMA nanodiscs, these proteins are well-suited for high-resolution structural analysis via cryo-EM, as well as for receptor-ligand binding assays and functional activity studies.7
Applications of Nanodiscs in Medicine
Drug Delivery
Nanodiscs offer an effective platform for enhancing drug delivery systems, particularly for drugs with low water solubility. Their lipid bilayer structure can encapsulate hydrophobic drugs, protecting them from premature degradation while enhancing their bioavailability.3
Chen et al. designed lipid nanodiscs functionalized with cyclic RGD peptide (cRGD) on either the edges or planes, creating two distinct anisotropic targeting nanocarriers (E-cRGD-NDs and P-cRGD-NDs) for siRNA delivery.8 E-cRGD-NDs demonstrated significant advantages in siRNA loading, cellular uptake, gene silencing efficiency, protein expression, and in vivo performance.
In a 2023 study, Yu et al. developed antibodies targeting matrix protein 2 (M2) of the influenza A virus. M2 (1-46) was incorporated into nanodiscs to form a membrane-embedded tetrameric structure, closely resembling its natural physiological state within the influenza virus envelope.9
Companies like Cube Biotech are actively developing nanodisc-based drug delivery systems that can be customized for different therapeutic needs. Its lipid-based nanodiscs offer a flexible platform for encapsulating and delivering various pharmaceuticals, including biologics and small-molecule drugs.
Vaccine Development
Nanodiscs have emerged as promising platforms for developing personalized tumor immunotherapy and vaccines against infectious diseases. They can be loaded with antigenic peptides or tumor markers, preserving the structure and activity of membrane proteins, which makes them highly immunogenic.1
Aldehyde dehydrogenase (ALDH) has been extensively used as a marker for isolating cancer stem cells (CSCs). These cells are characterized by high proliferation rates and play a role in tumor metastasis and recurrence.10 ALDH-positive CSCs have been identified in over 20 different tumor types.1
In a 2020 study, James J. Moon’s research group developed synthetic nanodiscs for vaccines targeting ALDHhigh CSCs. These nanodiscs improve antigen delivery to lymph nodes and trigger strong ALDH-specific T-cell responses, offering a promising new approach for cancer immunotherapy focused on CSCs.11
Diagnostic Tools
Nanodiscs offer considerable potential for creating advanced diagnostic tools. Their ability to stabilize membrane proteins in their native conformation makes them excellent tools for studying protein-protein interactions, enzymatic functions, and other cellular processes.12
NMR has long been used to gather structural information on soluble proteins. Rienstra and colleagues were the first to report solid-state NMR (ssNMR) spectra of nanodiscs, confirming that membrane scaffold proteins are organized in a “belt” configuration.13
Recently, there has been substantial growth in the use of both solution and ssNMR methods with nanodiscs, providing critical insights into the structure and function of membrane proteins. For instance, the complete three-dimensional structure of OmpX in nanodiscs, obtained through solution NMR, highlighted the ability to detect subtle conformational differences in a native bilayer environment.14
Conclusion
Nanodiscs represent a transformative innovation in medicine, with applications spanning protein stabilization, drug delivery, vaccine development, and diagnostics. Their ability to mimic natural cell membranes while remaining stable in various environments allows for broad applications in both research and clinical contexts.
Looking ahead, the future of nanodiscs in healthcare is strong. Continued research into polymer-based and MSP nanodiscs could lead to more robust and customizable platforms for therapeutic and diagnostic use.
As more companies and research institutions explore these applications, nanodiscs are likely to support more precise, effective, and personalized treatments in modern medicine.
References and Further Reading
1. Mu, Q., Deng, H., An, X., Liu, G. Liu, C. (2024). Designing nanodiscs as versatile platforms for on-demand therapy. Nanoscale. https://pubs.rsc.org/en/content/articlelanding/2024/nr/d3nr05457h
2. Nath, A., Atkins, WM. Sligar, SG. (2007). Applications of Phospholipid Bilayer Nanodiscs in the Study of Membranes and Membrane Proteins. Biochemistry. https://pubmed.ncbi.nlm.nih.gov/17263563/
3. Dong, Y., Tang, H., Dai, H., Zhao, H. Wang, J. (2024). The application of nanodiscs in membrane protein drug discovery & development and drug delivery. Front. Chem. https://pmc.ncbi.nlm.nih.gov/articles/PMC11445163/
4. Zhang, M. et al. (2021). Cryo-EM structure of an activated GPCR–G protein complex in lipid nanodiscs. Nat. Struct. Mol. Biol. https://pubmed.ncbi.nlm.nih.gov/33633398/
5. Frauenfeld, J. et al. (2016). A saposin-lipoprotein nanoparticle system for membrane proteins. Nat. Methods. https://pubmed.ncbi.nlm.nih.gov/26950744/
6. Chien, C.-T. H. et al. (2017). An adaptable phospholipid membrane mimetic system for solution NMR studies of membrane proteins. J. Am. Chem. Soc. https://pubmed.ncbi.nlm.nih.gov/28990386/
7. Swainsbury, DJK. et al. (2023). Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc 1 complex in styrene maleic acid nanodiscs. Proc. Natl. Acad. Sci. https://www.pnas.org/doi/10.1073/pnas.2217922120
8. Chen, X., Zhou, Y., Zhao, Y. Tang, W. (2023). Targeted degradation of extracellular secreted and membrane proteins. Trends Pharmacol. Sci. https://pubmed.ncbi.nlm.nih.gov/37758536/
9. Yu, C. et al. (2023). Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins. Iscience. https://pubmed.ncbi.nlm.nih.gov/36570769/
10. Marcato, P., Dean, CA., Giacomantonio, CA. Lee, PWK. (2011). Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell cycle. https://pubmed.ncbi.nlm.nih.gov/21552008/
11. Hassani Najafabadi, A. et al. (2020). Cancer immunotherapy via targeting cancer stem cells using vaccine nanodiscs. Nano Lett. https://pmc.ncbi.nlm.nih.gov/articles/PMC7572838/
12. Denisov, IG. Sligar, SG. (2017). Nanodiscs in membrane biochemistry and biophysics. Chem. Rev. https://pubmed.ncbi.nlm.nih.gov/28177242/
13. Li, Y., Kijac, AZ., Sligar, SG., Rienstra, CM. (2006). Structural analysis of nanoscale self-assembled discoidal lipid bilayers by solid-state NMR spectroscopy. Biophys. J. https://pubmed.ncbi.nlm.nih.gov/16905610/
14. Hagn, F., Wagner, G. (2015). Structure refinement and membrane positioning of selectively labeled OmpX in phospholipid nanodiscs. J. Biomol. NMR. https://pubmed.ncbi.nlm.nih.gov/25430058/
News
How the FDA opens the door to risky chemicals in America’s food supply
Lining the shelves of American supermarkets are food products with chemicals linked to health concerns. To a great extent, the FDA allows food companies to determine for themselves whether their ingredients and additives are [...]
Superbug crisis could get worse, killing nearly 40 million people by 2050
The number of lives lost around the world due to infections that are resistant to the medications intended to treat them could increase nearly 70% by 2050, a new study projects, further showing the [...]
How Can Nanomaterials Be Programmed for Different Applications?
Nanomaterials are no longer just small—they are becoming smart. Across fields like medicine, electronics, energy, and materials science, researchers are now programming nanomaterials to behave in intentional, responsive ways. These advanced materials are designed [...]
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
Scientists Flip a Gut Virus “Kill Switch” – Expose a Hidden Threat in Antibiotic Treatment
Scientists have long known that bacteriophages, viruses that infect bacteria, live in our gut, but exactly what they do has remained elusive. Researchers developed a clever mouse model that can temporarily eliminate these phages [...]
Enhanced Antibacterial Polylactic Acid-Curcumin Nanofibers for Wound Dressing
Background Wound healing is a complex physiological process that can be compromised by infection and impaired tissue regeneration. Conventional dressings, typically made from natural fibers such as cotton or linen, offer limited functionality. Nanofiber [...]
Global Nanomaterial Regulation: A Country-by-Country Comparison
Nanomaterials are materials with at least one dimension smaller than 100 nanometres (about 100,000 times thinner than a human hair). Because of their tiny size, they have unique properties that can be useful in [...]
Pandemic Potential: Scientists Discover 3 Hotspots of Deadly Emerging Disease in the US
Virginia Tech researchers discovered six new rodent carriers of hantavirus and identified U.S. hotspots, highlighting the virus’s adaptability and the impact of climate and ecology on its spread. Hantavirus recently drew public attention following reports [...]
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
Melting Arctic Ice May Unleash Ancient Deadly Diseases, Scientists Warn
Melting Arctic ice increases human and animal interactions, raising the risk of infectious disease spread. Researchers urge early intervention and surveillance. Climate change is opening new pathways for the spread of infectious diseases such [...]
Scientists May Have Found a Secret Weapon To Stop Pancreatic Cancer Before It Starts
Researchers at Cold Spring Harbor Laboratory have found that blocking the FGFR2 and EGFR genes can stop early-stage pancreatic cancer from progressing, offering a promising path toward prevention. Pancreatic cancer is expected to become [...]
Breakthrough Drug Restores Vision: Researchers Successfully Reverse Retinal Damage
Blocking the PROX1 protein allowed KAIST researchers to regenerate damaged retinas and restore vision in mice. Vision is one of the most important human senses, yet more than 300 million people around the world are at [...]
Differentiating cancerous and healthy cells through motion analysis
Researchers from Tokyo Metropolitan University have found that the motion of unlabeled cells can be used to tell whether they are cancerous or healthy. They observed malignant fibrosarcoma [...]
