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
DC60619	12T-O14	12T-O14 is a amidine-incorporated degradable (AID) lipid for versatile mRNA delivery. 12T-O14-LNPs mediate efficient intramuscular delivery of mRNA vaccines and systemic delivery of mRNA therapeutics without noticeable toxicity. 12T-O14 serves as a superior supplementary lipid to redirect liver-tropic LNPs to selectively target the lung or spleen via simple adjustment of the formulation. More description
DC52025	SM-102 Featured	SM-102 is an ionizable amino lipid that has been used in combination with other lipids in the formation of lipid nanoparticles.Administration of luciferase mRNA in SM-102-containing lipid nanoparticles induces hepatic luciferase expression in mice. Formulations containing SM-102 have been used in the development of lipid nanoparticles for delivery of mRNA-based vaccines. More description
DC42537	ALC-0315 Featured	ALC-0315 is an ionisable aminolipid that used for mRNA compaction and aids mRNA cellular delivery. ALC-0315 can be used to form lipid nanoparticle (LNP) delivery vehicles. More description
DC67785	KC3-OA Featured	KC3-OA, chemically known as 3-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, is an ionizable cationic lipid (ICL) optimized for lipid nanoparticle (LNP) formulations in nucleic acid delivery, particularly for mRNA vaccines. It features a unique structure with mono-unsaturated alkyl chains (C18:1), which enhances oxidative stability compared to polyunsaturated analogs like KC3, while maintaining efficient membrane fusion and endosomal escape capabilities. In LNP compositions, KC3-OA is typically incorporated at 46–54 mol% of total lipids, with an N/P ratio of 4–6 relative to mRNA, ensuring high encapsulation efficiency and transfection potency. Experimental data demonstrate that KC3-OA-based LNPs achieve superior mRNA expression in human dendritic cells, outperforming alternatives like KC3-PA or KC3-01 in both in vitro and in vivo models. For instance, in FIG. 2, KC3-OA LNPs showed ~2-fold higher mCherry expression at low mRNA doses (0.1 μg/mL) due to improved cellular uptake and reduced degradation. Its synergy with anionic phospholipids like DPPS (5 mol%) further enhances dendritic cell targeting via receptor-mediated internalization, leading to robust CD4+ and CD8+ T-cell responses against Mycobacterium tuberculosis antigens. This balance of stability, efficiency, and immunogenicity makes KC3-OA a leading candidate for next-generation vaccines. More description
DC67480	Sanofi Lipid VII	Lipid VII is a novel ionizable cationic lipid developed by Sanofi.Lipid VII demonstrates exceptional performance as a lipid nanoparticle delivery system, combining high efficiency with outstanding safety. Cellular assays reveal VII achieves 180,000 RLU transfection efficiency under serum conditions, surpassing traditional SS-OP systems by 2.25-fold while maintaining perfect 100% cellular viability and eliminating cytotoxicity risks that plague alternatives. In vivo systemic delivery shows rapid whole-body biodistribution, reaching photon emission levels exceeding 1.00E+10 photons/sec within 48 hours. VII exhibits superior organ targeting with a liver-specific accumulation ratio of 9.0, outperforming SS-OP systems by 50%, while reducing off-target spleen accumulation by 20%. Its versatility is further validated in therapeutic protein expression, where structural analogs achieve erythropoietin concentrations of 14 ng/mL, exceeding industry standards by 180%. For vaccine applications, VII generates a median HAI titer of 7,611 against H1N1 influenza—540 times higher than baseline buffers and more than double the next-best formulation. This evidence establishes VII as a breakthrough technology, offering unmatched efficiency, precision targeting, and clinical-grade safety across diverse applications. More description
DC66221	E12CA1A3	E12CA1A3 is an ionizable cationic lipid (pKa = 6.4) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo.1 LNPs containing E12CA1A3 and encapsulating an mRNA reporter induce luciferase reporter expression in mouse bone marrow-derived dendritic cells (BMDCs) and mice. LNPs containing E12CA1A3 are cleared more rapidly from the liver than LNPs containing DLin-MC3-DMA (Item No. 34364) in mice. More description
DC66219	Lipid 88 Featured	Lipid88 is a high-performance, novel ionizable lipid component engineered for advanced mRNA-LNP vaccine delivery. LNP88 formulation demonstrates superior biodistribution, achieving >10-fold higher transfection efficiency in spleen and lymph nodes compared to benchmark lipids like ALC-0315 via intramuscular delivery. When encapsulating antigen-encoding mRNA (e.g., optimized mCSA construct), Lipid-88 based LNPs drive robust humoral and cellular immunity, enabling complete protection against challenging SARS-CoV-2 variants (WA1/2020, Omicron BA.1, BQ.1) in preclinical models. Its design prioritizes potent immunogenicity with favorable safety profiles. More description
DC67536	Lipid A1-EP10-O18A	A1-EP10-O18A is an asymmetric ionizable lipid developed by Starna Therapeutics for mRNA vaccine delivery. Synthesized via Michael addition between amine alcohols and acrylates, its optimized structure—combining a hydrophilic C10 chain and hydrophobic unsaturated C18 tail—enables pH-dependent ionization. As the core component of the STAR0225 lipid nanoparticle (LNP) platform, it efficiently encapsulates mRNA and facilitates endosomal escape. Preclinical studies demonstrate superior in vivo mRNA delivery (vs. commercial SM102 LNPs), with enhanced local biodistribution and minimal off-target accumulation. This lipid underpins STR-V003, an RSV prefusion F mRNA vaccine showing robust immunogenicity and protection in animal models, supporting its clinical transition (NCT06344975). More description
DC60467	C12-TLRa	C12-TLRa is an adjuvant lipidoid. C12-TLRa substitution can enhance the immunogenicity of clinically relevant SARS-CoV-2 mRNA-LNP vaccines, which holds translational potential. More description
DC60839	A2T2C9 (CP-LC-1465) Featured	A2T2C9 (CP-LC-1465) is an imidazole-based ionizable lipid with branched hydrophobic chains and β-propionate linkers, formulated in four-component LNPs for spleen-targeted mRNA delivery. It achieves >80% spleen selectivity with protein expression exceeding 1×10⁷ p/s in mice, driven by its negative zeta potential (-9.7 to -19 mV). Structural features including imidazole polar head and branched acrylate (C9) enhance splenic tropism, potentially through distinct protein corona interactions. Demonstrated low cytotoxicity (>75% viability in splenic cells) and biodegradability via pH-sensitive linkers enable efficient mRNA delivery without permanent charged additives, outperforming conventional anionic SORT systems in selectivity and therapeutic potential. More description
DC67463	CP-LC-1428	Derived from the natural amino acid homocysteine, CP-LC-1428 is an ionizable cationic lipid that enables highly efficient in vivo delivery of multiple RNA formats (including mRNA, cRNA and saRNA) with robust protein expression. When formulated into standard LNPs (50:38.5:10:1.5 molar ratio of ionizable lipid:cholesterol:DOPE:PEG-lipid), it demonstrates superior spleen-selective targeting compared to conventional delivery systems following intravenous administration, while maintaining an excellent safety profile. More description
DC67460	CP-LC-1422	Derived from the natural amino acid homocysteine, CP-LC-1422 is an ionizable cationic lipid that enables robust in vivo delivery of various RNA forms (mRNA, cRNA, and saRNA), driving high protein expression. When formulated into LNPs (50/38.5/10/1.5 molar ratio of ionizable lipid/cholesterol/DOPE/PEG-lipid), it achieves superior spleen-specific targeting compared to commercial options through intravenous administration, while maintaining an excellent safety profile. More description
DC60828	YK-TLR-001 Featured	YK-TLR-001 is a cyclic acetal-based ionizable lipid for mRNA delivery. YK-TLR-001 LNPs are demonstrated to enhance mRNA expression in the spleens and to induce exceptional maturation of antigen-presenting cells (APCs) and to promote antigen presentation. More description
DC60684	Lipid I97	Lipid I97 is a vitamin B5-derived ionizable lipid for mRNA vaccine delivery. Lipid I97 LNP specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. More description
DC68030	C6mPhE-383 Featured	C6mPhE-383 is a top-performing ionizable lipid featuring an aromatic ring and a bioreducible disulfide bond. Formulated into lipid nanoparticles, it preferentially delivers mRNA to lymphoid tissues (lymph nodes/spleen) while minimizing off-target liver accumulation after intramuscular injection. In a SARS-CoV-2 vaccine study, it elicited strong antibody responses, promoted protective effector memory T cells, and exhibited enhanced safety by significantly reducing systemic inflammatory cytokines compared to the standard SM-102 LNP. More description
DC67633	Lipid KEL12	(4S)-KEL12 is a novel, biodegradable ionizable lipid developed for advanced mRNA vaccine delivery. It was rationally designed by incorporating both a ketal group in the linker and ester segments in the hydrophobic tails, a dual-degradable strategy aimed at enhancing its safety profile. Through iterative optimization, (4S)-KEL12 was identified as a lead candidate with an optimal pKa value of approximately 6.78, which is crucial for efficient mRNA encapsulation and endosomal release. More description
DC60925	Lipid H5T5 Featured	H5T5 is a leading ionizable lipid nanoparticle (LNP) formulation optimized for in vivomRNA delivery, featuring a pKa of 6.51, a size of ~154 nm, and a narrow polydispersity index (PDI) of 0.05. It demonstrated superior in vitromRNA transfection efficiency in primary immune cells, such as bone marrow-derived macrophages. Following intravenous administration, H5T5 exhibits precise organotropism, predominantly targeting the spleen and bone marrow, where it effectively delivers mRNA to a broad spectrum of immune cells, including macrophages, dendritic cells, T cells, B cells, and NK cells. This capability enables its core application: the in vivogeneration of "pan-CAR" immune cells. When loaded with anti-HER2 CAR mRNA, the H5T5-based therapy achieved potent tumor regression and prolonged survival in multiple solid tumor models. Preliminary safety assessments indicated a manageable cytokine profile and no significant organ toxicity, positioning it as a promising platform for in vivocell engineering. More description
DC60856	DMA4-H228 Featured	DMA4-H228 is a novel, biodegradable lipidoid specifically engineered for spleen-targeted mRNA delivery. Its structure combines a dimethylamino (DMA4) headgroup with a unique hyperbranched lipid tail (H228) synthesized via Michael addition, incorporating ester bonds for enhanced biodegradability. This design enables the formation of stable lipid nanoparticles (LNPs) (~170 nm) with high mRNA encapsulation efficiency (>96%). Critically, DMA4-H228 exhibits exceptional intrinsic tropism for the spleen (>98% targeting efficiency after IV administration), requiring no external targeting ligands. It selectively delivers mRNA to splenic antigen-presenting cells (APCs), including dendritic cells, macrophages, and B cells. This triggers potent immune activation: rapid IFNα secretion, upregulation of APC maturation markers (CD86/CD40), and robust antigen-specific immune responses. Demonstrating significant therapeutic potential, DMA4-H228-based mRNA vaccines effectively inhibit tumor growth in melanoma models (e.g., B16F10-OVA). This correlates with increased tumor-infiltrating CD8⁺ T cells, a shift towards pro-inflammatory M1 macrophages, elevated antigen-specific antibodies (IgG), and strong T cell responses (evidenced by IFNγ⁺ spots). Its ability to bypass liver tropism and directly activate splenic APCs makes DMA4-H228 a powerful platform for next-generation mRNA vaccines and cancer immunotherapy. More description
DC67450	A28-C6B2 Featured	A28-C6B2 is a biodegradable ionizable lipid specifically engineered for spleen-targeted delivery. Through its unique branched structure, it bypasses hepatic uptake to achieve highly efficient transfection of F4/80+ macrophages and CD11c+ dendritic cells within the spleen. This lipid remains neutral in the bloodstream to minimize non-specific interactions, while undergoing protonation in the acidic environment of the endosome to facilitate nucleic acid release, thereby significantly enhancing the potency of mRNA vaccines and immunotherapies. 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
DC60821	Lipid TOT-5 Featured	TOT-5, a tri-oleoyl-Tris ionizable lipid (pKa 6.2), enables splenic B cell-targeted mRNA delivery via 15% DSPC-incorporated LNPs. Its charge-neutral, hydrophobic surface minimizes hepatic ApoE uptake and enhances complement C3 adsorption, facilitating CD21/35-mediated uptake by marginal zone B cells. In vivo, intravenous 15%DSPC-LNPs showed 8-fold higher spleen-to-liver luciferase expression vs 3%DSPC, with anti-CD21/35 blocking 60% B cell uptake. Intramuscular administration induced robust OVA-specific IgG (10^5 titer) and CTL responses (3.5% tetramer+ CD8+ T cells) while reducing hepatotoxicity (ALT/AST levels ≤40 U/L vs SM-102-LNPs' 80-120 U/L). Cryo-ET confirmed stable lamellar structures (80-100 nm, ζ-potential -2 mV). This formulation achieves safe, ligand-free splenic targeting for mRNA vaccines. 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
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
DC80069	OF-DEG-LIN	OF-Deg-Lin is a biodegradable lipid containing an ester group, developed from the nonbiodegradable, linoleic acid derived OF-02; mRNA-LNPs containing OF-Deg-Lin showed high expression in the spleen. More description
DC82003	A12-Iso5-2DC18	A12-Iso5-2DC18 is a novel amine containing lipid can be used for mRNA delivery, activate the stimulator of interferon genes (STING) pathway, and exhibit anti-tumor immunity. More description
DC80071	A18-Iso5-2DC18 Featured	A18-Iso5-2DC18 that could not only deliver mRNA vaccines robustly but also activate the stimulator of interferon genes (STING) pathway. More description
DC80070	A2-Iso5-2DC18 Featured	A2-Iso5-2DC18 is a top-performing lipid for mRNA delivery in bone marrow-derived dendritic cells (BMDCs), BMDMs and HeLa cells. More description
DC60879	Lipid te AA3-Dlin Featured	TE AA3-Dlin is an optimized lipid nanoparticle (LNP) carrier designed for mRNA-based cancer immunotherapy, enabling precise in vivo dendritic cell (DC) reprogramming to enhance antitumor immunity. TE AA3-Dlin LNP exhibits superior serum stability, maintaining consistent particle size and low turbidity under physiological conditions, while protecting mRNA from degradation, which is crucial for effective delivery. Functionally, TE AA3-Dlin preferentially targets splenic DCs by leveraging ApoE-enriched protein coronas, facilitating efficient cellular uptake and mRNA expression, as demonstrated by enhanced EGFP signals in DCs.This targeting promotes DC maturation, antigen presentation, and membrane-bound IL-15 expression, activating cytotoxic T lymphocytes (CTLs) for tumor rejection. In models like melanoma and colon carcinoma, it synergizes with checkpoint inhibitors, showing minimal toxicity and robust immunological memory. More description
DC67615	STING Agonist Lipid SAL-12	SAL12 is a novel ionizable lipid derivative that integrates a non-nucleotide STING agonist (agonist 6) with an amino lipid tail through an ester bond, forming the core component of specialized lipid nanoparticles (SAL12-LNPs). These nanoparticles are designed for dual functionality: they efficiently encapsulate and deliver mRNA into dendritic cells while concurrently activating the STING pathway to stimulate innate immunity. More description
DC67537	DM3-BTA-14 Featured	DM3-BTA-14 is a cationic lipid compound engineered for high-efficiency mRNA delivery developed by Hefei AlphaNA Biotechnology. Its structure features a rigid benzene-1,3,5-tricarboxamide core linked to a protonatable dimethylamino headgroup (-N(CH₃)₂) via a propylene spacer (-CH₂CH₂CH₂-) and two saturated C14 alkyl chains. This design enables ≈90% endosomal escape efficiency , superior lymph node targeting for vaccines , and effective tumor-specific mRNA delivery . It outperforms benchmark lipids while maintaining low cytotoxicity, forming stable nanoparticles with cholesterol/DSPC/DSPE-PEG (50:39:10:1 ratio) for therapeutic applications. More description

Cationic/Ionizable Lipids

Customized Consultation X

Your information is safe with us. * Required Fields.