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
New mpox variant can spread rapidly across borders
International researchers, including from DTU National Food Institute, warn that the ongoing mpox outbreak in the Democratic Republic of the Congo (DRC) has the potential to spread across borders more rapidly. The mpox virus [...]
How far would you trust AI to make important decisions?
From tailored Netflix recommendations to personalized Facebook feeds, artificial intelligence (AI) adeptly serves content that matches our preferences and past behaviors. But while a restaurant tip or two is handy, how comfortable would you [...]
Can AI Really Think? Research Reveals Gaps in Logical Execution
While AI models can break down problems into structured steps, new research reveals they still fail at basic arithmetic and fact-checking—raising questions about their true reasoning abilities. Large Language Models (LLMs) have become indispensable [...]
Scientists Just Made Cancer Radiation Therapy Smarter, Safer, and More Precise
Scientists at UC San Francisco have developed a revolutionary cancer treatment that precisely targets tumors with radiation while sparing healthy tissues. By using a KRAS-targeting drug to mark cancer cells and attaching a radioactive [...]
Superbugs Are Losing to Science, Light, and a Little Spice
Texas A&M researchers have found that curcumin, when activated by light, can weaken antibiotic-resistant bacteria, restoring the effectiveness of conventional antibiotics. Curcumin: A Surprising Ally Against Superbugs In 2017, a woman admitted to a [...]
New Research Shatters the Perfect Pitch Myth
For decades, people believed absolute pitch was an exclusive ability granted only to those with the right genetics or early music training. But new research from the University of Surrey proves otherwise. It’s been [...]
Why Some Drinkers Suffer Devastating Liver Damage While Others Don’t
A study from Keck Medicine of USC found that heavy drinkers with diabetes, high blood pressure, or a large waistline are up to 2.4 times more likely to develop advanced liver disease. These conditions may amplify [...]
“Good” Cholesterol Could Be Bad for Your Eyes – New Study Raises Concerns
‘Good’ cholesterol may be linked to an increased risk of glaucoma in individuals over 55, while, paradoxically, ‘bad’ cholesterol may be associated with a lower risk. These findings challenge conventional beliefs about factors that [...]
Reawakening Dormant Nerve Cells: Groundbreaking Neurotechnology Restores Motor Function
A new electrical stimulation therapy for spinal muscle atrophy (SMA) has shown promise in reactivating motor neurons and improving movement. In a pilot clinical trial, three patients who received spinal cord stimulation for one [...]
AI’s Energy Crisis Solved? A Revolutionary Magnetic Chip Could Change Everything
AI is evolving at an incredible pace, but its growing energy demands pose a major challenge. Enter spintronic devices—new technology that mimics the brain’s efficiency by integrating memory and processing. Scientists in Japan have [...]
Nanotechnology for oil spill response and cleanup in coastal regions
(Nanowerk News) Cleaning up after a major oil spill is a long, expensive process, and the damage to a coastal region’s ecosystem can be significant. This is especially true for the world’s Arctic region, [...]
The Role of Nanotechnology in Space Exploration
Nanotechnology, which involves working with materials at the atomic or molecular level, is becoming increasingly important in space exploration. By improving strength, thermal stability, electrical conductivity, and radiation resistance, nanotechnology is helping create lighter, more [...]
New Study Challenges Beliefs About CBD in Pregnancy, Reveals Unexpected Risks
CBD is gaining popularity as a remedy for pregnancy symptoms like nausea and anxiety, but new research suggests it may not be as safe as many believe. A study from McMaster University found that [...]
Does COVID increase the risk of Alzheimer’s disease?
Scientists discover that even mild COVID-19 can alter brain proteins linked to Alzheimer’s disease, potentially increasing dementia risk—raising urgent public health concerns. A recent study published in the journal Nature Medicine investigated whether both mild and [...]
New MRI Study Reveals How Cannabis Alters Brain Activity and Weakens Memory
A massive new study sheds light on how cannabis affects the brain, particularly during cognitive tasks. Researchers analyzed over 1,000 young adults and found that both heavy lifetime use and recent cannabis consumption significantly reduced brain [...]
How to Assess Nanotoxicity: Key Methods and Protocols
With their high surface area and enhanced physicochemical properties, nanomaterials play a critical role in drug delivery, consumer products, and environmental technologies. However, their nanoscale dimensions enable interactions with cellular components in complex and [...]
