How Are Drugs Delivered? Lipid Nanoparticles
How Are Drugs Delivered? Lipid Nanoparticles
Nucleic acid molecules such as mRNA and siRNA are susceptible to nuclease degradation, cannot readily cross cell membranes, and may become trapped within endosomes after endocytosis. Lipid nanoparticles (LNPs) establish a cytosolic delivery pathway through nucleic acid encapsulation, nanoparticle-mediated transport, and endosomal escape. Ionizable lipids, helper phospholipids, cholesterol, and PEG lipids perform distinct functions and collectively determine delivery efficiency, stability, and tissue distribution.
Keywords: lipid nanoparticle; LNP; mRNA delivery; siRNA delivery; ionizable lipid; endosomal escape; PEG lipid
1 Nucleic Acid Delivery Challenges Addressed by LNPs
1.1 Major Delivery Barriers for Nucleic Acid Therapeutics
(1) Extracellular degradation and clearance
Naked DNA and RNA are highly hydrophilic and negatively charged, making them susceptible to degradation by nucleases in biological fluids. They may also interact with plasma proteins and innate immune recognition systems. Through lipid–nucleic acid assembly, LNPs reduce direct contact between nucleic acids and the extracellular environment, converting readily degradable nucleic acids into nanoparticulate cargoes capable of transport within biological environments.
(2) Cell membrane barrier
Nucleic acid molecules cannot readily cross the hydrophobic cell membrane. LNPs promote particle uptake through their surface properties, the protein corona formed after exposure to biological fluids, and different cellular endocytic pathways, thereby providing macromolecules such as mRNA and siRNA with a route into cells. However, this process only resolves the challenge of cellular entry and does not indicate that the nucleic acid has reached the cytosol.
(3) Endosomal entrapment
After entering early endosomes through endocytosis, LNPs are transported into increasingly acidic intracellular compartments as the endosomes mature. If the cargo cannot escape in time, the particles may continue into late endosomes and lysosomes, where the nucleic acid is ultimately degraded. For mRNA and siRNA, which primarily function in the cytosol, endosomal escape is a major rate-limiting step in functional delivery.
1.2 Technical Boundaries Between Liposomes and Nucleic Acid LNPs
(1) Classical liposomes
Classical liposomes generally consist of one or more lipid bilayers enclosing an aqueous compartment. Hydrophilic molecules can be encapsulated in the internal aqueous phase, whereas hydrophobic molecules can enter the hydrophobic region of the lipid bilayer. Their principal design considerations include drug encapsulation, membrane stability, circulation time, and tissue exposure, making them suitable for various small molecules, proteins, and certain nucleic acid cargoes.
(2) Nucleic acid LNPs
Modern nucleic acid LNPs are generally assembled from ionizable lipids, helper phospholipids, cholesterol, and PEG lipids. Their interiors do not necessarily form typical hollow bilayer vesicles but may instead contain complex lipid–nucleic acid structures. Their design priorities extend to nucleic acid binding, particle self-assembly, in vivo transport, endosomal escape, and cytosolic release. Nucleic acid LNPs therefore cannot simply be equated with classical liposomes.
Table 1 Major Differences Between Liposomes and Nucleic Acid LNPs
Comparison Dimension | Classical Liposomes | Nucleic Acid Delivery LNPs |
Major structural features | Lipid bilayers enclosing an aqueous compartment | Complex lipid–nucleic acid nanostructures |
Main cargoes | Small molecules, proteins, and certain nucleic acids | Nucleic acids such as mRNA and siRNA |
Key materials | Phospholipids, cholesterol, PEG lipids, etc. | Ionizable lipids, helper phospholipids, cholesterol, and PEG lipids |
Core technical challenges | Encapsulation, membrane stability, pharmacokinetics | Nucleic acid encapsulation, endocytosis, endosomal escape, and cytosolic release |
Representative applications | Liposomal small-molecule drugs | siRNA therapeutics, mRNA vaccines, and mRNA therapies |
2 Functional Division Among the Four Core Lipid Classes in LNPs
2.1 Ionizable Lipids: Nucleic Acid Encapsulation and Endosomal Escape
(1) pH-dependent charge conversion
Permanently cationic lipids such as DOTAP and DOTMA remain positively charged under physiological conditions and can form complexes with negatively charged nucleic acids. However, persistent positive charge also enhances nonspecific interactions with plasma proteins and cell membranes. Ionizable lipids use protonatable amine groups to achieve dynamic charge regulation. Their overall charge approaches neutrality near physiological pH but becomes positive again under acidic conditions, thereby balancing nucleic acid binding, biocompatibility, and intracellular membrane activity.
(2) Nucleic acid encapsulation under acidic conditions
LNPs are generally assembled rapidly under mildly acidic conditions. At this stage, ionizable lipids become protonated, form electrostatic interactions with the phosphate backbone of nucleic acids, and promote the incorporation of mRNA or siRNA into the particle interior. After particle formation and transfer to an environment near physiological pH, the net positive charge of the ionizable lipids decreases, reducing nonspecific interactions caused by a persistently cationic surface during circulation.
(3) Membrane disruption in the endosomal environment
After LNPs enter acidified endosomes, ionizable lipids become protonated again and interact more strongly with anionic phospholipids in the endosomal membrane. The resulting lipid ion pairs can alter the local geometric organization and curvature of membrane lipids, destabilizing the bilayer structure and creating conditions that allow nucleic acids to enter the cytosol. Ionizable lipids therefore participate in the two critical stages of nucleic acid loading and nucleic acid release.
2.2 Helper Phospholipids: Particle Architecture and Membrane Phase Behavior
(1) Stabilizing helper phospholipids
Saturated phospholipids such as DSPC exhibit a high degree of membrane order and can participate in forming the lipid architecture of LNPs while improving particle stability. Fatty-acyl chain length, saturation, and phase-transition properties affect the compactness of the hydrophobic region and consequently alter particle rigidity, membrane fluidity, and storage stability.
(2) Fusogenic helper phospholipids
Phosphatidylethanolamine lipids such as DOPE have a pronounced tendency to form non-bilayer phases and can more readily generate highly curved structures, thereby affecting fusion and membrane rearrangement between lipid particles and endosomal membranes. Helper phospholipids must be selected to balance particle stability with membrane dynamics.
2.3 Cholesterol: Lipid Packing and Membrane Fluidity
Cholesterol can insert into the hydrophobic acyl-chain regions of other lipids, fill intermolecular spaces, and regulate membrane fluidity, lipid packing, and particle compactness. An appropriate cholesterol content helps maintain LNP structural integrity and reduce cargo leakage. Modifying the sterol backbone or introducing different functional groups can further regulate membrane charge, curvature, internal structure, and in vivo distribution.
2.4 PEG Lipids: Particle-Size Control and Surface Interface
(1) Control of particle growth
PEG lipids consist of a hydrophobic anchor and a hydrophilic PEG chain. The lipid moiety inserts into the particle, whereas the PEG chain extends into the aqueous phase to generate steric hindrance, thereby limiting further particle fusion and growth. An excessively low PEG-lipid proportion can increase aggregation and broaden the particle-size distribution, whereas an excessively high proportion may create a strong surface barrier that reduces effective interactions between particles and cell membranes.
(2) Regulation of colloidal and circulatory stability
The PEG layer can reduce direct particle–particle contact and some nonspecific protein adsorption, thereby improving dispersion stability and circulation behavior. PEG chain length, lipid anchoring structure, and retention time on the particle surface collectively influence this effect, and different PEG lipids cannot simply be treated as equivalent materials.
(3) Construction of functionalized surfaces
Materials such as DSPE-PEG-MAL and DSPE-PEG-NH2 retain reactive functional groups at the PEG terminus and can be used to conjugate peptides, proteins, or other targeting ligands. These materials extend the function of the PEG layer from a purely steric stabilizing interface to a platform for surface functionalization and active targeting.
Table 2 Functional Division Among the Four Core Lipid Classes in LNPs
Component | Main Challenge Addressed | Core Function |
Ionizable lipid | How to load nucleic acids and release them from endosomes | Binds nucleic acids under acidic conditions and promotes membrane disruption in the endosomal environment |
Helper phospholipid | How to maintain an appropriate particle membrane structure | Regulates membrane stability, fluidity, and curvature |
Cholesterol | How to achieve stable lipid packing | Fills the lipid structure and regulates membrane fluidity |
PEG lipid | How to control particle size and reduce aggregation | Restricts particle fusion, regulates the surface interface, and provides functionalization sites |
3 Complete LNP Delivery Pathway from Preparation to Cytosolic Release
3.1 Rapid Acidic Mixing and Particle Assembly
(1) Particle nucleation
Nucleic acids are generally placed in an acidic aqueous phase, whereas ionizable lipids, helper phospholipids, cholesterol, and PEG lipids are dissolved in a suitable organic phase. Following rapid mixing of the two phases, protonated ionizable lipids first bind the nucleic acids, while hydrophobic lipids simultaneously aggregate and self-assemble to form lipid–nucleic acid nanostructures.
(2) Particle growth
Mixing rate, phase flow-rate ratio, total lipid concentration, nucleic acid concentration, and PEG-lipid proportion collectively control particle nucleation and subsequent growth. Changes in processing conditions are directly reflected in particle size, polydispersity index (PDI), encapsulation efficiency, and internal structure. Identical lipid formulations therefore do not necessarily produce identical delivery performance.
3.2 In Vivo Transport and Cellular Uptake
(1) Protein corona formation
After entering biological fluids, LNPs rapidly adsorb plasma proteins, lipoproteins, and other biomolecules to form a dynamic protein corona. The interface that actually participates in tissue distribution and cellular recognition consists of both the original lipid surface and the adsorbed biomolecules. Lipid composition therefore not only alters the particle itself but also indirectly changes its biological interface.
(2) Cellular endocytosis
After reaching a tissue, particles can enter cells through different endocytic pathways. Uptake efficiency is jointly influenced by particle size, surface properties, lipid composition, protein corona, and cell type. Increasing the intracellular particle content only indicates enhanced endocytosis and does not directly demonstrate a corresponding increase in mRNA expression or siRNA-mediated silencing.
3.3 Endosomal Escape: A Critical Step in Functional Delivery
(1) Endosomal acidification
As endosomes mature, their luminal pH gradually decreases. Ionizable lipids become protonated again and interact more strongly with anionic endosomal membrane lipids. This stage is the critical point at which ionizable lipids transition from a relatively neutral state during circulation back to a membrane-active state.
(2) Lipid ion pairs and membrane rearrangement
After protonated ionizable lipids form ion pairs with anionic phospholipids, they can alter the effective molecular geometry and membrane curvature of local lipid molecules, causing the stable bilayer to adopt highly curved or non-bilayer arrangements. As local membrane integrity decreases, the particle cargo gains an opportunity to cross the endosomal membrane and enter the cytosol.
(3) Nucleic acid entry into the cytosol
After successfully entering the cytosol, mRNA can be translated by ribosomes, whereas siRNA can enter the molecular machinery responsible for RNA interference. Functional LNP delivery is determined not by whether particles are taken up by cells but by how much intact nucleic acid crosses the endosomal membrane while retaining biological activity.
3.4 Hierarchical Interpretation of Cellular Uptake and Effective Delivery
Particle uptake, endosomal escape, cytosolic bioavailable cargo, and final functional output represent distinct delivery levels. An increase in intracellular LNP signals only demonstrates increased particle uptake and cannot be used to infer endosomal escape efficiency, the amount of intact nucleic acid in the cytosol, or the final effects on mRNA expression and siRNA-mediated silencing. LNP evaluation should therefore use corresponding indicators for different delivery levels rather than substituting a single particle-uptake measurement for functional delivery outcomes.
4 Key Parameters Determining LNP Delivery Efficiency
4.1 Ionizable Lipid Structure and pKa
(1) Headgroup ionization behavior
The chemical environment of the ionizable amine determines the apparent pKa of the lipid. An excessively high pKa may cause the lipid to retain excessive positive charge in the circulatory environment, increasing nonspecific interactions. An excessively low pKa may result in insufficient protonation within the endosomal environment. An appropriate ionization window must balance acidic assembly, stability under physiological conditions, and endosomal membrane activation.
(2) Hydrophobic tail chains
Tail-chain length, degree of unsaturation, number, and branching pattern determine hydrophobic lipid packing and molecular geometry. Unsaturated bonds or branched chains can alter membrane fluidity and curvature propensity and further affect particle structure and endosomal membrane disruption. However, increased membrane activity does not necessarily result in a corresponding increase in particle stability.
(3) Linker structures
The linker group between the headgroup and hydrophobic tails influences lipid flexibility, stability, and metabolism. Introducing hydrolyzable or metabolizable structures can facilitate material clearance after delivery, whereas excessively rapid degradation may impair formulation storage and in vivo transport. Stability and metabolizability must therefore be balanced.
4.2 Helper Lipids and Cholesterol
(1) Phase behavior of helper lipids
Different helper lipids, including DSPC, DOPE, and DOPC, differ substantially in acyl-chain saturation, headgroup structure, and phase-transition behavior. Highly ordered helper lipids help stabilize particles, whereas lipids with a stronger tendency to form non-bilayer phases can enhance membrane rearrangement. Formulations should be selected according to the nucleic acid type and endosomal release requirements.
(2) Cholesterol proportion and structure
Cholesterol improves the integrity of lipid packing and regulates membrane fluidity. However, changes in its proportion simultaneously alter particle rigidity, cargo leakage, and membrane fusion behavior. Cholesterol derivatives can further modify LNP internal organization and biodistribution through differences in polar groups and molecular geometry.
4.3 Bidirectional Effects of the PEG Proportion
Increasing the PEG-lipid proportion generally restricts particle growth and aggregation, decreases the mean particle size, improves the PDI, and enhances colloidal stability. When the surface PEG density becomes excessively high, however, the steric barrier may restrict contact between LNPs and cellular or endosomal membranes, resulting in increased particle stability but decreased effective delivery. Optimizing PEG content therefore requires balancing formulation stability with biological membrane interactions.
4.4 Particle Size, PDI, and Encapsulation Efficiency
Particle size and PDI reflect particle dimensions and uniformity and affect tissue distribution, cellular uptake, and formulation reproducibility. High encapsulation efficiency helps reduce exposure to free nucleic acids. However, high encapsulation efficiency cannot replace functional evaluation. LNP performance must also be assessed by integrating nucleic acid integrity, particle stability, cellular uptake, endosomal escape, and final expression or silencing outcomes.
5 Representative Applications of LNPs in Drug Delivery
5.1 siRNA Delivery
siRNA is susceptible to nuclease degradation and cannot readily cross cell membranes because of its negative charge. LNPs can improve both the extracellular stability and intracellular delivery of siRNA, enabling it to participate in RNA interference after entering the cytosol. The clinical application of patisiran validated the feasibility of ionizable lipid LNPs for systemic siRNA delivery and established an important technological foundation for modern nucleic acid LNPs.
5.2 mRNA Vaccines and mRNA Therapeutics
mRNA does not need to enter the nucleus but must remain intact and reach the cytosol before it can be translated by ribosomes. mRNA-LNPs must sequentially complete cargo protection, nanoparticle-mediated transport, tissue distribution, cellular uptake, and endosomal escape. The large-scale application of COVID-19 mRNA vaccines further demonstrated the technical maturity of four-component systems comprising ionizable lipids, helper phospholipids, cholesterol, and PEG lipids for mRNA delivery.
5.3 Lipid-Mediated Delivery of Small Molecules
PEGylated liposomal doxorubicin is a classical liposomal drug formulation rather than a typical nucleic acid LNP. Its main function is to alter the pharmacokinetics and tissue exposure of doxorubicin through liposomal encapsulation. This application demonstrates the technological foundation of lipid nanocarriers for small-molecule delivery and also illustrates the clear differences between classical liposomes and modern nucleic acid LNPs in cargo properties, internal structure, and intracellular release objectives.
6 Products Related to LNP Preparation, Membrane Regulation, and Tracing
6.1 Ionizable, Cationic, and PEG-Functionalized Lipids
Catalog # | Product Name | Grade & Purity | Product Description | Role in LNPs/Research Application |
ALC-0315 | Moligand™, ≥98% | An ionizable lipid containing protonatable amine groups that can alter its charge state according to environmental pH | Used for mRNA-LNP assembly, nucleic acid encapsulation, and endosomal escape-related studies | |
D-Lin-MC3-DMA | ≥98% | A classical ionizable lipid for nucleic acid delivery that enhances interactions with nucleic acids and membrane lipids under acidic conditions | Used to construct LNPs for siRNA and other nucleic acids and investigate pH-responsive delivery | |
1,2-Dioleoyl-3-trimethylammonium-propane, Chloride (DOTAP Chloride) | Moligand™, ≥99% | A permanently cationic lipid that forms complexes with nucleic acids through the positive charge of its quaternary ammonium group | Used to construct DNA/RNA complexes, cationic liposomes, and transfection systems | |
1,2-di-O-octadecenyl-3-trimethylammonium propane chloride salt (DOTMA) | ≥98% | A cationic ether lipid containing two hydrophobic chains and a quaternary ammonium headgroup | Used for nucleic acid complexation, cationic lipid particles, and transfection studies | |
Trimethyl[2,3-(dioleyloxy)propyl]ammonium Chloride | ≥90% | A double-hydrophobic-chain quaternary ammonium cationic lipid | Used to regulate positive surface charge and nucleic acid complexation capacity in lipid particles | |
Dimethyldioctadecylammonium bromide | ≥98% | A quaternary ammonium cationic lipid containing two long-chain hydrophobic groups | Used for cationic lipid membrane assembly and studies of surface charge and nucleic acid complexation | |
Octadecylamine | ≥97%(GC) | A long-chain amine containing a C18 hydrophobic chain and a terminal primary amine | Used for lipid membrane amination, surface-charge regulation, and functionalization studies | |
ALC-0159 | Moligand™, ≥98% | A PEG lipid containing a hydrophobic anchoring moiety and a hydrophilic PEG chain | Used for LNP particle-size control, aggregation suppression, and surface PEG-layer formation | |
MPEG2000-DSPE Sodium Salt | MW 2000 Da | A DSPE-anchored PEG2000 phospholipid that can insert into the surface of lipid particles | Used for PEGylated liposomes, LNP surface stabilization, and regulation of circulation properties | |
DSPE PEG Maleimide, DSPE-PEG-MAL | MW 2000 Da | A functionalized PEG phospholipid containing a terminal maleimide group | Used to conjugate thiol-containing peptides, proteins, or other ligands and construct functionalized surfaces | |
DSPE PEG Amine, DSPE-PEG-NH2 | MW 2000 Da | A DSPE-PEG functional lipid containing a terminal amino group | Used for LNP or liposome surface conjugation and targeting modification |
6.2 Helper Phospholipids, Cholesterol, and Membrane Property-Regulating Materials
Catalog # | Product Name | Grade & Purity | Product Description | Role in LNPs/Research Application |
1,2-distearoyl-sn-glycero-3-phosphocholine （DSPC） | Moligand™, ≥99% | A phosphatidylcholine containing two saturated C18 acyl chains | Commonly used as an LNP helper phospholipid to improve particle structural stability | |
1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine （DOPE） | ≥99%, 10 mg phospholipid per ml CHCl3,TLC | A phosphatidylethanolamine containing two unsaturated acyl chains and exhibiting a strong tendency to form non-bilayer phases | Used to investigate membrane curvature, membrane fusion, and endosomal membrane disruption | |
1,2-distearoyl-sn-glycero-3-phosphoethanolamine | ≥97% | A phosphatidylethanolamine containing two saturated C18 chains and exhibiting strong membrane-anchoring capacity | Used for studies of liposomal structures and PEG-functionalized lipid scaffolds | |
1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) | Moligand™, ≥99% | A phosphatidylethanolamine containing two saturated C16 chains | Used for membrane structure, helper lipid, and surface functionalization studies | |
1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine | ≥98% | A phosphatidylethanolamine containing two C14 acyl chains | Used to compare the effects of acyl-chain length on membrane fluidity and phase behavior | |
1,2-dioleoyl-sn-glycero-3-phosphocholine | Moligand™, ≥99% | A phosphatidylcholine containing unsaturated acyl chains and exhibiting relatively high membrane fluidity | Used for fluid lipid membranes, liposomes, and formulation comparison studies | |
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine（POPC） | ≥99% | A phosphatidylcholine containing both saturated and unsaturated acyl chains | Used to simulate biological membranes and regulate lipid membrane fluidity | |
1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC) | ≥99% | A phosphatidylcholine containing saturated C14 acyl chains | Used for studies of membrane phase transitions, fluidity, and lipid particle structure | |
DPPC | Moligand™, 10 mM in Ethanol | A phosphatidylcholine containing saturated C16 acyl chains | Used for liposomes, model membranes, and phospholipid phase-transition studies | |
L-α-phosphatidylcholine (95%) (Egg, Chicken) | Native, ≥95% | A naturally derived phosphatidylcholine mixture | Used to construct conventional liposomes and natural phospholipid membrane systems | |
Phosphatidylcholine, hydrogenated from Non-GMO Soybean(HSPC) | Native, ≥90% | A hydrogenated soybean-derived phosphatidylcholine with a relatively high degree of acyl-chain saturation | Used to construct highly stable lipid membranes and liposomal systems | |
Cholesterol | for cell culture, ≥99%(GC) | A natural sterol that inserts into the hydrophobic region of phospholipids and regulates lipid organization | Used to regulate LNP membrane fluidity, compactness, and structural stability | |
Cholesteryl hemisuccinate(CHEMS) | Moligand™, ≥97% | A cholesterol derivative containing a hemisuccinate structure | Used to investigate the regulation of membrane charge, pH responsiveness, and lipid phase behavior | |
1,2-dioleoyl-sn-glycero-3-phospho-L-serine (sodium salt)（DOPS） | Moligand™, ≥99% | A negatively charged unsaturated phosphatidylserine | Used to construct anionic membrane environments and investigate cationic lipid–membrane interactions | |
1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) | ≥97% | A long-chain saturated anionic phosphatidylglycerol | Used to regulate negative surface charge and membrane stability in lipid particles | |
1,2-Dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt | ≥99%(TLC) | An anionic phosphatidylglycerol containing two saturated C16 chains | Used to investigate liposome surface charge and membrane phase behavior | |
1,2-Dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt | ≥99% | An anionic phospholipid containing unsaturated acyl chains | Used for studies of fluid anionic membranes, membrane fusion, and charge effects | |
1,2-dioleoyl-sn-glycero-3-phosphate (sodium salt) (18:1 PA) | ≥99% | A phosphatidic acid containing a relatively small polar headgroup and unsaturated acyl chains | Used to investigate membrane curvature, anionic membrane lipids, and lipid rearrangement |
6.3 Products for LNP Tracing, Membrane Localization, and Release Evaluation
Catalog # | Product Name | Grade & Purity | Product Description | Role in LNPs/Research Application |
1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate(DiI) | for fluorescence analysis, ≥98% | A lipophilic carbocyanine fluorescent dye containing long hydrophobic chains that can insert into lipid membranes | Used for LNP membrane labeling, cellular uptake, and particle tracing | |
3,3'-Dioctadecyloxacarbocyanine perchlorate | ≥98% | A lipophilic oxacarbocyanine fluorescent probe that localizes to the hydrophobic region of lipid membranes | Used for lipid membrane labeling, particle uptake, and membrane localization studies | |
DIA (cell membrane green fluorescent probe) |
| A green lipophilic cell membrane fluorescent probe that can insert into lipid membranes | Used for LNP membrane labeling, cellular uptake, and lipid particle localization | |
Did (cell membrane red fluorescent probe) |
| A red to far-red lipophilic membrane fluorescent probe | Used for LNP tracing, cellular localization, and multicolor fluorescence analysis | |
DiD | ≥98% | A far-red lipophilic carbocyanine dye that can insert into the hydrophobic region of lipid membranes | Used for lipid particle membrane labeling, cellular uptake, and tissue distribution evaluation | |
DiR' [DiIC18(7)] | ≥95% | A near-infrared lipophilic carbocyanine dye that can stably distribute within lipid membranes | Used for in vivo LNP imaging and studies of tissue enrichment and biodistribution | |
Calcein indicator | Metal indicator | A water-soluble fluorescent molecule that can serve as an internal aqueous-phase cargo in lipid vesicles | Used to evaluate encapsulation, membrane leakage, and membrane permeability | |
6-Carboxyfluorescein | ≥95% | A water-soluble fluorescein derivative that can be used to establish encapsulation and release signal systems | Used to investigate lipid-carrier leakage, encapsulation, and cargo release |
The central determinant of LNP delivery efficiency is not whether particles enter cells but whether intact nucleic acids can undergo stable transport, cellular uptake, and endosomal escape to reach the cytosol. Ionizable lipids determine nucleic acid encapsulation and membrane-disrupting capacity, whereas helper phospholipids, cholesterol, and PEG lipids collectively regulate particle structure, stability, and the biological interface.
References
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