Cationic/Ionizable Lipids

In the past five years, DC Chemicals has focused on research and development in the RNA delivery field, successfully developing over 500 cationic lipid structures and maintaining an inventory of over 200 cationic lipids. We collaborate with leading gene delivery companies and research institutions worldwide, and our products and services have received widespread acclaim.
DC Chemicals has accumulated substantial experience in the synthesis of lipids, particularly for highly complex lipid molecules. Our unique chemical synthesis and purification processes often circumvent patented and literature-reported routes, allowing us to design new synthetic routes that yield lipid molecules with higher purity than those reported in literature and patents. Our representative molecules, such as LP-01, SM-102, ALC-0315, and DLIN-MC3-DMA, have purities exceeding 98% as tested by CAD-HPLC, placing them among the top purity products available.We have the capability to scale production from grams to kilograms.

Cationic ionizable lipids play a major role in the LNP formulation and its ability to transfect target cells with its cargo. The ionizable lipids are used to complex negatively charged nucleic acid cargo. The mRNA-cationic lipid complex fuses with the cell membrane and is then delivered into the cytosol. To be able to play these roles efficiently, a cationic ionizable lipid must be engineered with a suitable apparent acid dissociation constant (pKa). The apparent pKa of a cationic ionizable lipid is the likely pKa at the LNP surface. Currently, the cationic ionizable lipids in FDA-approved therapeutics all have an apparent pKa between 6-7. This is crucial for the cationic ionizable lipid to maintain a neutral charge while in systemic circulation (pH above the pKa of the lipid, pH ~7.5), as well as its ability to become positively charged in the endosome (pH ~6.5) and facilitate membrane fusion and subsequent cytosolic release.

You can also try the following methods, and our professionals will serve you Customized Consultation

Cat. No.	Product Name	Field of Application
DC68151	KC-34 (SPC-A9) Featured	KC-34 (SPC-A9) is a novel stereopure, diketopiperazine-based ionizable cationic lipid engineered to overcome traditional liver-restricted delivery, achieving balanced multi-organ mRNA transfection. Upon systemic intravenous administration, its precisely optimized chiral configuration allows the lipid nanoparticles (LNPs) to efficiently cross endothelial barriers and target the bone marrow, offering immense therapeutic potential for in vivo hematopoietic stem cell gene editing. Concurrently, KC-34 mediates robust and long-lasting protein expression in the spleen and lungs with minimal hepatic off-target toxicity. Its stable structure provides excellent biocompatibility and high in vivo tolerance, making it ideal for systemic, multi-dose mRNA therapies. More description
DC67569	Lipid S4 Featured	Lipid S4 is an advanced ionizable lipid engineered for systemic mRNA delivery to the brain, leveraging SR-57227—a high-affinity 5-HT3 receptor ligand—as its core head group to enable targeted blood-brain barrier (BBB) penetration via receptor-mediated transcytosis, while incorporating amino linkers for pH-responsive ionization and biodegradable branched ester tails to facilitate efficient endosomal escape and intracellular mRNA release; optimized through orthogonal screening into OS4 LNP (formulated at S4/DOPE/Chol/DMG-PEG2k = 40:40:60:0.75 molar ratio), it demonstrated a 13.3-fold increase in brain mRNA expression compared to FDA-approved MC3 LNPs, and further conjugation with the Tat cell-penetrating peptide yielded OS4T LNP, boosting delivery efficiency by 12.7-fold over OS4 alone and enabling broad mRNA expression across neurons, astrocytes, microglia, and endothelial cells; validated in orthotopic glioblastoma models, OS4T delivered engineered IL-12 mRNA, suppressing tumor growth and extending median survival to 37 days (vs. 17 days for controls) with minimal systemic toxicity, positioning S4-based LNPs as a robust, translatable platform for CNS-targeted therapeutics. More description
DC68208	Sail lipid 7669 Featured	Lipid 7669 is a premium, spleen-tropic ionizable lipid highly validated in US2025/0049948A1 for targeted mRNA delivery. Engineered for extrahepatic targeting, it achieves exceptional splenic protein expression while minimizing hepatic accumulation, significantly outperforming conventional liver-targeting lipids like MC3 and C12-200. In vivo bioluminescence data confirms its superior whole-body transfection efficiency and highly selective spleen tropism. This high-performance lipid is ideal for pioneering research in mRNA vaccines, splenic immune editing, and autoimmune disease therapies requiring precise extrahepatic delivery. Lipid 7669 is for research purpose. More description
DC67556	Lipid 2308 Featured	Sail Lipid 2308 is a novel ionizable lipid targeting to spleen developed by Sai Biomedicine.As described on US20250205167A1, Lipid 2308 was designed with a piperidine core (6-membered ring) and asymmetric C17/C11 chains, this lipid achieves unprecedented spleen-specificity. It demonstrates dominant spleen accumulation (Spleen RLU: 7.8E+06, 91.8% of total signal) with a record spleen-to-liver ratio of 112.7 (9× higher than 2231). Despite lower protein expression (hEPO: 11,000 ng/mL), near-zero liver uptake (Liver RLU: 66,000) makes Lipid 2308 unparalleled for vaccine/immunotherapy applications targeting splenic immune cells. More description
DC67555	Lipid 2231 Featured	Sail Lipid 2231 is a novel ionizable lipid targeting to spleen developed by Sai Biomedicine.As described on US20250205167A1 Lipid 2231 features a pyrrolidine core (5-membered ring) with biodegradable ester linkages and asymmetric C17/C11 hydrophobic chains. In vivo data shows moderate spleen targeting (Spleen RLU: 3.8E+06) with a spleen-to-liver ratio of 12.767. More description
DC68207	Q1-SM-102 iodide Featured	Q1-SM-102 iodide is a quaternary ammonium lipid derivative of SM-102 (HY-13454). Q1-SM-102 iodide can be used to prepare lipid nanoparticles (LNPs) for the delivery of mRNA in vivo. Q1-SM-102 iodide is a carriers for targeting delivery of mRNA to immune organs. More description
DC60929	Lipid 2310 Featured	Lipid 2310 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 5.58 and a very high total expression level of 1.3E+07. Lipid 2310 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen. More description
DC60928	Lipid 2306 Featured	Lipid 2306 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 3.68 and a very high total expression level of 2.5E+07. Lipid 2306 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen. More description
DC82209	Lipid 10a-26 Featured	Lipid 10a-26 is an ionizable lipid developed by Orna Therapeutics for lipid nanoparticle (LNP) formulations. Lipid 10a-26 is a key ionizable lipid in the LNP-6 formulation. Through structural modification, it exhibits reduced binding to ApoE proteins and lowered liver affinity compared to traditional ionizable lipids. Instead, Lipid 10a-26 demonstrates strong splenic tropism—in non-human primate studies, it effectively delivers payloads to the spleen and immune cells in peripheral blood, such as T cells, NK cells, and macrophages, enabling the possibility of "in vivo CAR-T" therapy. Its pKa is tuned to approximately 6.0–6.5, allowing rapid protonation in the acidic endosomal environment, which promotes endosomal membrane disruption and efficient cytosolic release of circular RNA. More description
DC67109	Fluorescent SM-102 (NBD-SM-102) Featured	Fluorescent SM-102 (NBD-SM-102) is a premium, dye-conjugated ionizable cationic lipid designed for advanced nanomedicine and mRNA delivery research. By covalently integrating a bright, green-fluorescent nitrobenzofurazan (NBD) probe into the industry-standard SM-102 skeleton, this high-purity reagent operates as an indispensable visual tracer. It empowers researchers to seamlessly track cellular uptake, monitor tissue biodistribution, and quantify endosomal escape efficiencies via fluorescence microscopy and flow cytometry. Crucially, this NBD-SM-102 derivative preserves the native ionizable property (\(pK_a \approx 6.68\)) and optimal membrane-fusion dynamics required for lipid nanoparticle (LNP) assembly and transfection, ensuring experimental formulations accurately mimic functional delivery vectors. This reliable reagent is ideal for accelerating lipid-mix optimization, high-throughput screening, and nucleic acid therapeutics development pipeline. More description
DC68190	SM-102 azide Featured	SM-102 azide is an azide-modified derivative of the clinically validated SM-102 ionizable lipid. Designed specifically for advanced Lipid Nanoparticle (LNP) formulation, this product integrates a reactive azide (-N₃) group to enable effortless, high-yield functionalization via click chemistry. It is the ideal tool for researchers and developers looking to construct targeted nucleic acid delivery systems, build diverse lipid libraries, or track LNPs in vivo. More description
DC68205	CA-20 Featured	CA-20 is a bile acid-derived sterol designed to replace cholesterol in mRNA LNPs. It achieves high mRNA encapsulation efficiency up to 87.4% and forms uniform, spherical nanoparticles with ordered membrane structures confirmed by cryo-TEM and MD simulations. In vivo, CA-20 drastically cuts hepatic mRNA expression while shifting nearly all gene expression to the spleen, driven by reduced ApoE protein binding on LNP surfaces. Using HA mRNA vaccines, CA-20 LNPs trigger stronger antigen-specific IgG, neutralizing antibodies, memory B cells and IFN-γ-secreting T cells than cholesterol LNPs. Acute safety tests prove CA-20 causes minimal liver damage, with normal serum liver enzymes and intact organ histology, delivering balanced superior immunogenicity and low liver toxicity for spleen-targeted mRNA vaccine delivery. More description
DC67605	PyCB lipid Featured	PyCB lipid (MeDZ) is a rationally designed zwitterionic ionizable lipid that serves as a core functional component in the novel three-component (ThrCo) lipid nanoparticle (LNP) platform. It is synthesized by covalently attaching a zwitterionic PyCB structure to the hydroxyl group of the clinically available ionizable lipid ALC-0315.Its key feature is its pH-responsive behavior. At physiological pH (~7.4), the PyCB headgroup exhibits zwitterionic properties, forming charge-assisted hydrogen bonds with water molecules (PyCB-H₂O complexes). This confers high hydrophilicity to the LNP surface, enhancing stability in aqueous environments and reducing nonspecific protein adsorption in the bloodstream. This zwitterionic surface effectively mimics and replaces PEGylated lipids, thereby avoiding PEG immunogenicity and the associated Accelerated Blood Clearance (ABC) effect upon repeated administrations.Crucially, in the acidic environment of endosomes (pH ~6.5), the PyCB group undergoes strong protonation, rapidly transforming into a cationic state (PyCB-H₃O⁺ complexes). This promotes efficient fusion with and disruption of the endosomal membrane, facilitating the escape and cytoplasmic release of encapsulated mRNA.By replacing both cholesterol and PEGylated lipids in traditional LNPs, PyCB lipid enables the redirection of LNP biodistribution from the liver to the spleen, achieving superior spleen-specific mRNA translation and enhancing antigen presentation for potent immune activation. More description
DC60564	Lipid GVS-18-B6 Featured	GVS-18-B6 is a silicon ether-based ionizable lipid (pKa:6.15) developed by Genevant, optimized for mRNA-LNP delivery, characterized by a short-chain trialkyl structure with three C10 alkyl chains (including a cis double bond) and a dimethylamino (DMA) head group linked via a 4-carbon spacer (pKa ~6.15). Its LNP formulations exhibit a narrow particle size distribution (89 nm, PDI=0.06), high mRNA encapsulation efficiency (90%), and pH-dependent surface charge (−0.11 mV at pH 7.5 vs. +2.69 mV at pH 5.5), facilitating endosomal escape. In vivo, GVS-18-B6 demonstrated superior liver-specific mRNA expression (5.30×10⁷ pg EGFP/g liver, 2.6× higher than MC3) with minimal spleen accumulation (liver/spleen ratio 92:1 vs. MC3’s 10:1), attributed to rapid non-enzymatic hydrolysis of its silicon ether bonds. This mechanism enables near-complete hepatic clearance within 6 hours in mice and 24 hours in NHPs, avoiding long-term organ retention (MC3 retained 25% in liver after 28 days). Compared to benchmarks (MC3, SM-102, LP-01), GVS-18-B6 showed enhanced potency in RBC hemolysis assays (pH 6.2), indicating earlier endosomal membrane disruption, and maintained stability through 12-month frozen storage or repeated freeze-thaw cycles. Toxicity profiling revealed minimal immunogenicity (MCP-1 levels 0.58×10⁶ vs. MC3’s 1.10×10⁶) and no ALT/AST elevation or anti-PEG antibody induction in NHPs after repeated dosing. Its species-agnostic clearance, low off-target effects, and high tolerability (6 mg/kg dose in mice) position GVS-18-B6 as a leading candidate for chronic disease therapies requiring frequent mRNA administration. More description
DC68179	A5-CE-C7−6 Featured	A5-CE-C7-6 is an ionizable lipid engineered for spleen-targeted mRNA delivery, integrating a hydroxylated dual-amine core (A5) for enhanced mRNA binding and endosomal escape, a biodegradable carbonate ester linker (CE) enabling rapid hydrolysis (61% degradation in 24 h), and branched heptyl hydrophobic tails (C7-6) that optimize nanoparticle stability and spleen tropism. When formulated into cholesterol-free lipid nanoparticles (B-8 formulation), its unique architecture—combining hydroxyl groups for cellular uptake, carbonate-mediated biodegradability, and branched-chain fluidity—achieves unprecedented efficiency: low pKa (~6.0) minimizes liver accumulation while enabling 21% transfection of splenic NK cells, outperforming benchmark systems like MC3 SORT LNPs by >10-fold in spleen-specific delivery and establishing a new standard for in vivo immune cell engineering. More description
DC67540	Lipid A5-CE-C7-6(3 tail) Featured	A5-CE-C7-6 (3-tail analog) is a structural control compound derived from the standard 2-tail lipid(A5-CE-C7-6), with three carbonate alkyl chains linked to the A5 amine core. More description
DC60941	Antioxidant lipid AO12 Featured	AO12 is a novel antioxidant ionizable lipid derived from SM-102 skeleton with para-hydroxyphenyl propionic acid side chains. Integrated into LNPs, it efficiently scavenges diverse reactive oxygen species including ·OH and ONOO⁻, shielding encapsulated mRNA from oxidative degradation. It retains fine LNP formulation features and cellular uptake capacity of conventional lipids, boosting in vivo mRNA translation. Applied for regenerative mRNA therapy and CRISPR gene editing against fibrosis and inflammatory disorders. More description
DC67553	Lipid PL40 Featured	PL-40 is a cardiolipin-mimetic ionizable lipid engineered for high-efficiency, antibody-free mRNA delivery to T cells. PL 40 LNPs exhibit a mean particle size of 120 nm, zeta potential of -5.19 mV, and >80% mRNA encapsulation efficiency, with excellent plasma stability (≤5% size change after 6h in serum). Cryo-TEM reveals polyhedral nanoparticles with phase-separated domains, while SAXS confirms tight mRNA packing (d-spacing: ~3 nm vs. 6.64 nm in conventional LNPs). AFM demonstrates exceptional rigidity (high bending modulus), enabling T cell-selective uptake via actin-mediated endocytosis (>2× higher than ALC0315 LNPs).In primary human T cells, PL40 LNPs achieve >90% transfection at 0.5 μg mRNA dose and sustain >100× higher luciferase expression than benchmark lipids. When delivering circular RNA, they extend protein expression >5 days with superior spleen tropism (spleen:liver ratio = 2.63). Crucially, they reprogram T cells into functional CAR-Ts in vivo without antibody conjugation, evading exhaustion markers (no Tim-3/PD-1 upregulation). Therapeutically, PL40-based uPAR-targeted CAR mRNA reduces liver fibrosis (collagen↓50%, ALT↓50%) and rheumatoid arthritis severity (clinical scores↓60%) by clearing senescent cells. Humanized anti-uPAR CARs delivered via PL40 show near-complete cytotoxicity (>95%) against uPAR+ cells, underscoring clinical translatability. More description
DC60947	Lilly lipid 51 Featured	Lipid 51 is a top-performing thioglycerol-based biodegradable ionizable lipid disclosed in PCT patent WO2026/147683 (Eli Lilly, filed Dec 16, 2025). Built with cleavable thioester linkages, it balances neutral surface charge at physiological pH and protonatable amines in acidic endosomes for efficient mRNA encapsulation and endosomal escape. Formulated into LNPs with DSPC, cholesterol and DMG-PEG2K, it exhibits favorable particle size, low PDI and high RNA loading efficiency. In intracerebroventricular (ICV) mouse tests targeting central nervous system (CNS), it delivers Cre mRNA to brain neurons far more potently than Lipid 1/2/3, with the highest tissue fluorescent signal among all tested candidates. It shows low cellular toxicity in vitro and robust CNS tropism, making it an optimal carrier for brain-targeted mRNA and CRISPR gene editing therapeutics. More description
DC67568	ORNA Lipid AX-6 Featured	AX6 is an ionizable lipid in the F32 LNP formulation, engineered by ReNAgade/Orna Therapeutics for targeted mRNA delivery to T cells. AX-6's unique bridged bicyclic/polycyclic core with a tertiary amine group enables pH-dependent protonation and endosomal escape, while C14-C18 hydrophobic tails (optionally branched/fluorinated) enhance bilayer stability and mRNA encapsulation. Demonstrating exceptional T-cell tropism, AX6 achieves high transfection efficiency in CD4+/CD8+ T cells (validated in NHP/humanized models) with minimal toxicity. Compared to clinical benchmarks (SM-102, ALC-0315), its rigid core offers superior serum stability and immune-cell specificity, positioning it as an ideal candidate for CAR-T/NK therapies and next-gen vaccines. The F32 LNP system's proven efficacy (e.g., in vivo B-cell depletion) underscores AX 6's transformative potential for cell engineering and immunotherapies. More description
DC68057	Lipid Trp-L1-T4 Featured	Trp-L1-T4 is a novel tryptophan-derived ionizable lipid that serves as the core functional component of the optimized lipid nanoparticle (TLNP/RLNP) platform. Its primary function is to enable the efficient encapsulation and in vivo delivery of self-amplifying RNA (saRNA) cargo. Specifically, it facilitates high transfection efficiency and cytosolic release of the RNA payload in target follicular helper T (Tfh) cells, with minimal cytotoxicity. This capability is crucial for reprogramming pathogenic Tfh cells into regulatory CAR-Tfh cells, forming the foundation of the study's therapeutic strategy. More description
DC67566	CureVac Lipid C24(CVL1,VitE-C4DE-Pip- S) Featured	CVL1 (C24) is an ionizable lipid developed by CureVac for mRNA delivery, featuring a vitamin E (α-tocopherol) core linked via a thioether bridge to piperidine-based cationic headgroups. Its unique design enables pH-dependent charge switching (neutral at physiological pH, cationic in endosomes) for efficient mRNA encapsulation and endosomal escape. Formulated in lipid nanoparticles (LNPs) with DPhyPS and PMOZ4, CVL1 preferentially targets spleen and lymph node dendritic cells (DCs), enhancing antigen presentation and T-cell immunity. Key advantages include high mRNA encapsulation (>90%), stability under lyophilization, and reduced liver accumulation compared to PEGylated LNPs. In preclinical studies, CVL1-based LNPs induced robust CD8+/CD4+ T-cell responses and IgG2a-dominant antibody titers against tumor antigens (e.g., Trp2). With a particle size of 70–120 nm and low polydispersity (PDI <0.2), CVL1 balances delivery efficiency and biocompatibility, making it ideal for cancer and infectious disease vaccines requiring strong cellular immunity. Its degradable ester and thioether bonds further improve safety profiles. More description
DC68177	L52715 Featured	L52715 is a novel ionizable lipid developed by Shanghai Vitalgen, used to deliver mRNA. More description
DC60463	MIC2 Featured	MIC2 is a set of multi-charged lipids with four tertiary amino nitrogen atoms (4N4T) which could be constructed and applied to form novel lipid nanoparticles. 4N4T-LNPs based on MIC2 exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. 4N4T-LNPs are successfully applied to DS mRNA vaccine and the vaccines worked well against SARS-CoV-2 and its variants, including Delta and Omicron. More description
DC60537	C18 NC-TNP Featured	C18 NC-TNP is a novel noncationic thiourea lipid without positively charged groups. It binds nucleic acids via hydrogen bonds instead of electrostatic attraction, avoiding cation-triggered systemic inflammation. Formulated into nanoparticles, it efficiently encapsulates mRNA, siRNA and plasmids, shows excellent serum tolerance and long-term liquid/lyophilized storage stability. It enters cells mainly through macropinocytosis, escapes endosomes intact to reduce nucleic acid degradation. In vivo, it targets spleen preferentially, induces robust long-lasting Th1-type cellular and humoral immunity with minimal organ toxicity, superior to SM102 LNPs for mRNA cancer vaccine delivery. More description
DC68141	AMG514 Featured	AMG514 is a novel ionizable lipid designed for formulating spleen-targeting lipid nanoparticles (LNPs) to deliver immune‑remodeling mRNAs (IR‑mRNAs). Its key advantage lies in the formation of a unique “protein corona” enriched with vitronectin, coagulation factors, and specific apolipoproteins (e.g., ApoA‑IV), together with its relatively high apparent pKa (~7.5), which actively redirects LNPs to the spleen instead of the liver. This precise spleen‑targeting property enables efficient transfection of splenic antigen‑presenting cells (APCs). As a vaccine adjuvant, AMG514‑LNPs therefore elicit a more robust activation of adaptive immunity compared to conventional LNPs (e.g., cKK‑E12), generating significantly enhanced antigen‑specific CD8⁺ T‑cell and antibody responses, and inducing durable anti‑tumor immune memory in preclinical models. More description
DC60809	6Ac1-C12 Featured	6Ac1-C12 is an ionizable cationic lipid with a hexaester degradable core and six C12 hydrophobic alkyl tails, featuring a pKa around 6.0 and strong endosomal escape capacity. Its four-component LNPs deliver mRNA mainly to liver endothelial cells after IV injection and remain stable for 30 days at 4°C. Formulated without cholesterol, its three-component system enables lung-targeted delivery with low in vivo toxicity, and the ester core facilitates biodegradation for versatile mRNA applications. More description
DC60942	113-AA-C8C14 Featured	113-AA-C8C14 is a spleen-tropic ionizable lipid with inherent splenic organ selectivity. Its formulated LNPs drastically reduce off-target liver uptake and drive 57-fold higher mRNA expression in spleen versus benchmark LNPs. It preferentially delivers nucleic acids to splenic immune cells like macrophages and T lymphocytes, supporting in vivo CAR-T engineering and mRNA vaccine research with minimal accumulation in other visceral organs. More description
DC80066	306Oi10 Featured	306Oi10 is a branched ionizable lipid that can be used to construct lipid nanoparticles (LNPs) for delivering messenger RNA. The surface ionization of lipid nanoparticles is related to the effectiveness of mRNA delivery. The tail of 306Oi10 has a one-carbon branch, which provides it with stronger surface ionization compared to lipids with linear tails, thereby enhancing its mRNA delivery efficacy. 306Oi10 can be used in research related to mRNA delivery. More description
DC65619	Lipid 11-A-M Featured	Lipid 11-A-M (LNP Lipid-8) is a specialized single-tail, multi-head ionizable cationic lipid engineered for targeted nucleic acid delivery to T cells. Unlike traditional lipids that exhibit strong liver tropism, 11-A-M formulations successfully bypass hepatocytes, resulting in negligible liver accumulation and toxicity. Upon intravenous administration, it naturally localizes to peripheral immune organs, enabling robust gene silencing and transfection specifically within splenic CD3⁺ T cells, with a higher efficiency in CD8⁺ cytotoxic T cells over CD4⁺ helper T cells. This liver-evading, T cell-specific targeting profile makes it a premier tool for in vivo immunotherapy and in situ cell reprogramming. More description

Cationic/Ionizable Lipids

Customized Consultation X

Your information is safe with us. * Required Fields.