Lipidoid Nanoparticles Research Articles

Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets.

Lipidoid nanoparticles (LNPs) have transformed the field of drug delivery and are clinically used for the delivery of nucleic acids to liver and muscle targets. Post-intravenous administration, LNPs are naturally directed to the liver due to the adsorption of plasma proteins like apolipoprotein E. In the present work, we have re-engineered LNPs with ionic liquids (ILs) to reduce plasma protein adsorption and potentially increase the accumulation of LNPs in hard-to-deliver central nervous system (CNS) targets such as brain endothelial cells (BECs) and neurons. We have developed two approaches to re-engineer LNPs using a choline trans-2-hexenoate IL: first, we have optimized an IL-coating process using the standard LNP formulation and in the second approach, we have incorporated ILs into the LNPs by replacing the PEG-lipid component in the standard formulation using ILs. IL-coated as well as IL-incorporated LNPs were colloidally stable with morphologies similar to the standard LNPs. IL-coated LNPs showed superior uptake into mouse BECs and neurons and demonstrated reduced mouse plasma protein adsorption compared to the standard LNPs. Overall, our results (1) demonstrate the feasibility of re-engineering the clinically approved LNP platform with highly tunable biomaterials like ILs for the delivery of therapeutics to CNS targets like BECs and neurons and (2) suggest that the surface properties of LNPs play a critical role in altering their affinity to and uptake into hard-to-deliver cell types.

Factor XII Silencing Using siRNA Prevents Thrombus Formation in a Rat Model of Extracorporeal Life Support.

Heparin anticoagulation increases the bleeding risk during extracorporeal life support (ECLS). This study determined whether factor XII (FXII) silencing using short interfering RNA (siRNA) can provide ECLS circuit anticoagulation without bleeding. Adult male, Sprague-Dawley rats were randomized to four groups (n = 3 each) based on anticoagulant: (1) no anticoagulant, (2) heparin, (3) FXII siRNA, or (4) nontargeting siRNA. Heparin was administered intravenously before and during ECLS. FXII or nontargeting siRNA were administered intravenously 3 days before the initiation of ECLS via lipidoid nanoparticles. The rats were placed on pumped, arteriovenous ECLS for 8 hours or until the blood flow resistance reached three times its baseline resistance. Without anticoagulant, mock-oxygenator resistance tripled within 7 ± 2 minutes. The resistance in the FXII siRNA group did not increase for 8 hours. There were no significant differences in resistance or mock-oxygenator thrombus volume between the FXII siRNA and the heparin groups. However, the bleeding time in the FXII siRNA group (3.4 ± 0.6 minutes) was significantly shorter than that in the heparin group (5.5 ± 0.5 minutes, p < 0.05). FXII silencing using siRNA provided simpler anticoagulation of ECLS circuits with reduced bleeding time as compared to heparin. http://links.lww.com/ASAIO/A937.

Lipidoid nanoparticles increase ATP uptake into hypoxic brain endothelial cells

Lipidoid nanoparticles (LNPs) are clinically successful carriers for nucleic acid delivery to liver and muscle targets. The ability of LNPs to load and deliver small molecule drugs has not been reported yet. We propose that the delivery of adenosine triphosphate (ATP) to brain endothelial cells (BECs) lining the blood–brain barrier may increase cellular energetics of the injured BECs. We formulated and studied the physicochemical characteristics of ATP-loaded LNPs using the C12-200 ionizable cationic lipid and other helper lipids. Polyethylene glycol-dimyristoyl glycerol (PEG-DMG), one of the helper lipids, played a crucial role in maintaining colloidal stability of LNPs over time whereas the inclusion of both ATP and PEG-DMG maintained the colloidal stability of LNPs in the presence of serum proteins. ATP-LNPs formulated with PEG-DMG resulted in a 7.7- and 6.6- fold increased uptake of ATP into normoxic and hypoxic BECs, respectively. Altogether, our results demonstrate the potential of LNPs as a novel carrier for the delivery of small molecular mass actives to BECs—a CNS target.

The replacement of helper lipids with charged alternatives in lipid nanoparticles facilitates targeted mRNA delivery to the spleen and lungs.

The broad clinical application of mRNA therapeutics has been hampered by a lack of delivery vehicles that induce protein expression in extrahepatic organs and tissues. Recently, it was shown that mRNA delivery to the spleen or lungs is possible upon the addition of a charged lipid to a standard four-component lipid nanoparticle formulation. This approach, while effective, further complicates an already complex drug formulation and has the potential to slow regulatory approval and adversely impact manufacturing processes. We were thus motivated to maintain a four-component nanoparticle system while achieving shifts in tropism. To that end, we replaced the standard helper lipid in lipidoid nanoparticles, DOPE, with one of eight alternatives. These lipids included the neutral lipids, DOPC, sphingomyelin, and ceramide; the anionic lipids, phosphatidylserine (PS), phosphatidylglycerol, and phosphatidic acid; and the cationic lipids, DOTAP and ethyl phosphatidylcholine. While neutral helper lipids maintained protein expression in the liver, anionic and cationic lipids shifted protein expression to the spleen and lungs, respectively. For example, replacing DOPE with DOTAP increased positive LNP surface charge at pH7 by 5-fold and altered the ratio of liver to lung protein expression from 36:1 to 1:56. Similarly, replacing DOPE with PS reduced positive charge by half and altered the ratio of liver to spleen protein expression from 8:1 to 1:3. Effects were consistent across ionizable lipidoid chemistries. Regarding mechanism, nanoparticles formulated with neutral and anionic helper lipids best transfected epithelial and immune cells, respectively. Further, the lung-tropic effect of DOTAP was linked to reduced immune cell infiltration of the lungs compared to neutral or anionic lipids. Together, these data show that intravenous non-hepatocellular mRNA delivery is readily achievable while maintaining a four-component formulation with modified helper lipid chemistry.

Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer.

Diabetes mellitus is a chronic manifestation characterized by high levels of glucose in the blood resulting in several complications including diabetic wounds and ulcers, which predominantly require a longer duration of treatment and adversely affect the quality of life of the patients. Nanotechnology-based therapeutics (both intrinsic and extrinsic types) have emerged as a promising treatment in diabetic foot ulcer/chronic wounds owing to their unique characteristics and specific functional properties. In this review, we have focused on the significance of the use of lipids in the healing of diabetic ulcers, their interaction with the injured skin, and recent trends in lipid-based nanocarriers for the healing of diabetic wounds. Lipid nanocarriers are also being investigated for gene therapy in diabetic wound healing to encapsulate nucleic acids such as siRNA and miRNA, which could silence the expression of inflammatory cytokines overexpressed in chronic wounds. Additionally, these are also being explored for encapsulating proteins, peptides, growth factors, and other biological genetic material as therapeutic agents. Lipid-based nanocarriers encompassing a wide variety of carriers such as liposomes, niosomes, ethosomes, solid lipid nanoparticles, and lipidoid nanoparticles that are explored for the treatment of foot ulcers supplemented with relevant research studies have been discussed in the present review. Lipid-based nanodrug delivery systems have demonstrated promising wound healing potential, particularly in diabetic conditions due to the enhanced efficacy of the entrapped active molecules.

Chemical Modification of Proteins and Their Intracellular Delivery Using Lipidoid Nanoparticles.

Protein-based therapeutics are a class of drugs considered to be one of most safe and straightforward approaches for manipulating cell function and treating diseases. However, in contrast to traditional small-molecule drugs, most protein drugs cannot easily pass through biological membrane barriers due to their large size and surface chemistry. Consequently, most of the current FDA approved protein pharmaceuticals target secreted domains or cell surface-bound receptors, for which the drug does not need to pass through the cell membrane. Effective delivery systems that can transport functionally intact protein molecules to their intracellular targets can contribute to further expanding the therapeutic modalities of protein-based drugs. Furthermore, proteins themselves can be engineered, either to facilitate their interaction with the delivery system, or to improve their specificity and efficacy upon intracellular delivery. Both physical and biochemical methods have been developed for intracellular protein delivery and each strategy has its own advantages and drawbacks. We describe here the methods of chemical modification of therapeutic proteins in combination of the lipid-like molecules or lipidoids to enhance their intracellular delivery efficiency.

Development of Lipidoid Nanoparticles for siRNA Delivery to Neural Cells.

Lipidoid nanoparticles (LNPs) are the delivery platform in Onpattro, the first FDA-approved siRNA drug. LNPs are also the carriers in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While these applications have demonstrated that LNPs effectively deliver nucleic acids to hepatic and muscle cells, it is unclear if LNPs could be used for delivery of siRNA to neural cells, which are notoriously challenging delivery targets. Therefore, the purpose of this study was to determine if LNPs could efficiently deliver siRNA to neurons. Because of their potential delivery utility in either applications for the central nervous system and the peripheral nervous system, we used both cortical neurons and sensory neurons. We prepared siRNA-LNPs using C12-200, a benchmark ionizable cationic lipidoid along with helper lipids. We demonstrated using dynamic light scattering that the inclusion of both siRNA and PEG-lipid provided a stabilizing effect to the LNP particle diameters and polydispersity indices by minimizing aggregation. We found that siRNA-LNPs were safely tolerated by primary dorsal root ganglion neurons. Flow cytometry analysis revealed that Cy5 siRNA delivered via LNPs into rat primary cortical neurons showed uptake levels similar to Lipofectamine RNAiMAX—the gold standard commercial transfection agent. However, LNPs demonstrated a superior safety profile, whereas the Lipofectamine-mediated uptake was concomitant with significant toxicity. Fluorescence microscopy demonstrated a time-dependent increase in the uptake of LNP-delivered Cy5 siRNA in a human cortical neuron cell line. Overall, our results suggest that LNPs are a viable platform that can be optimized for delivery of therapeutic siRNAs to neural cells.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1208/s12248-021-00653-2.

Osteogenic effects of microRNA-335-5p/lipidoid nanoparticles coated on titanium surface

ObjectiveIn this study, we aimed to investigate the therapeutic potential of miR-335-5p lipidoid nanocomplexes coated on Titanium (Ti) SLActive surface by lyophilization. DesignIn our model, we coated miR-335-5p/Lipidoid nanoparticles on titanium implant, seeded GFP-labelled mouse bone marrow stromal cells (BMSCs) onto the functionalized Ti implant surface, and analyzed the transfection efficiency, cell adhesion, proliferation, and osteogenic activity of the bone-implant interface. ResultsThe Ti SLActive surface displayed a suitable hydrophilicity ability and provided a large surface area for miRNA loading, enabling spatial retention of the miRNAs within the nanopores until cellular delivery. We demonstrated a high transfection efficiency of miR-335-5p lipidoid nanoparticles in BMSCs seeded onto the Ti SLActive surface, even after 14 days. Alkaline phosphatase (ALP) activity and cell vitality were significantly increased in BMSCs transfected with miR-335-5p at 7 and 14 days as opposed to cells transfected with negative controls. When miR-335-5p transfected BMSCs were induced to undergo osteogenic differentiation, we detected increased mRNA expression of osteogenic markers including Alkaline phosphatase (ALP), collagen I (COL1), osteocalcin (OCN) and bone sialoprotein (BSP) at 7 and 14 days as compared with negative controls. ConclusionMiR-335-5p lipidoid nanoparticles could be used as a new cost-effective methodology to increase the osteogenic capacity of biomedical Ti implants.

In situ cancer vaccination using lipidoid nanoparticles.

In situ vaccination is a promising strategy for cancer immunotherapy owing to its convenience and the ability to induce numerous tumor antigens. However, the advancement of in situ vaccination techniques has been hindered by low cross-presentation of tumor antigens and the immunosuppressive tumor microenvironment. To balance the safety and efficacy of in situ vaccination, we designed a lipidoid nanoparticle (LNP) to achieve simultaneously enhancing cross-presentation and STING activation. From combinatorial library screening, we identified 93-O17S-F, which promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist). Intratumor injection of 93-O17S-F/cGAMP in combination with pretreatment with doxorubicin exhibited excellent antitumor efficacy, with 35% of mice exhibiting total recovery from a primary B16F10 tumor and 71% of mice with a complete recovery from a subsequent challenge, indicating the induction of an immune memory against the tumor. This study provides a promising strategy for in situ cancer vaccination.

Development of an activated microglia cell line model for screening lipid nanoparticle formulations of BDNF siRNA for neuropathic pain therapy

Purpose Brain-derived neurotrophic factor (BDNF) released from activated spinal microglia via the ATP-P2 × 4R-BDNF signaling pathway plays a central role in initiating pain hypersensitivity in neuropathic pain. Therefore, knockdown of BDNF expression in microglia using molecules like siRNA can be a promising strategy for neuropathic pain therapy. Our lab is developing lipidoid nanoparticles (LNP) for the delivery of BDNF siRNA (siBDNF) for treating neuropathic pain. We characterized the Spontaneously Immortalized Microglia-A9 (SIM-A9) cell line and confirmed the expression of Iba1, P2 × 4R, and BDNF under resting (non-activated) and ATP-stimulated conditions. SIM-A9 cell line was cultured with and without external stimuli, adenosine triphosphate (ATP), and/or lipopolysaccharide (LPS) by varying parameters such as the concentration of stimuli, incubation time, and cell regeneration time post-activation. The cytocompatibility of SIM-A9 cells with ATP and LPS was determined using an ATP assay. Intracellular Iba1, P2 × 4R, and BDNF protein expression in the resting and stimulated cells were characterized using western blotting, in-cell western, and immunocytochemistry. In a pilot study, SIM-A9 cells were transfected with RNAiMAX (a commercial transfection agent)/siBDNF complexes and changes in BDNF expression were evaluated using western blotting. We present two novel findings: first, SIM-A9 cells expressed P2 × 4R and BDNF proteins. Second, ATP at a safe dose showed a time-dependent increase in Iba1 and BDNF expression without intracellular toxicity. At 40 nM siRNA concentration, RNAiMAX/siBDNF complexes showed about a 15% reduction in SIM-A9 BDNF expression. In preliminary studies, LNP/siBDNF at 40 nM were well-tolerated by SIM-A9 cells, however, they only showed negligible BDNF knockdown in activated SIM-A9 cells. Currently, we are optimizing LNP formulations and transfection conditions to increase the extent of BDNF gene silencing. We have developed an ATP-activated SIM-A9 cell line model system that can be utilized for screening of neuropathic pain therapeutics.

MRNA Delivery Using Bioreducible Lipidoid Nanoparticles Facilitates Neural Differentiation of Human Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and tissue engineering and delivering biological molecules into MSCs has been used to control stem cell behavior. However, the efficient delivery of large biomolecules such as DNA, RNA, and proteins into MSCs using nonviral delivery strategies remains an ongoing challenge. Herein, nanoparticles composed of cationic bioreducible lipid-like materials (lipidoids) are developed to intracellularly deliver mRNA into human mesenchymal stem cells (hMSCs). The delivery efficacy to hMSCs is improved by adding three excipients including cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG) during lipidoid nanoparticle formulation. Using an optimized lipidoid formulation, Cas9 mRNA and single guide RNA (sgRNA) targeting neuron restrictive silencing factor (NRSF) are delivered to hMSCs, leading to successful neural-like differentiation as demonstrated by the expression of synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and neuron-specific growth-associated protein (SCG10). Overall, a synthetic lipid formulation that can efficiently deliver mRNA to hMSCs is identified, leading to CRISPR-based gene knockdown to facilitate hMSCs transdifferentiation into neural-like lineage.

Inhibition of retinal neovascularization by VEGF siRNA delivered via bioreducible lipid-like nanoparticles.

Previously, we have demonstrated the use of lipidoid (lipid-like) nanoparticles (e.g., "1-O16B") for gene delivery to live cells, as an alternative to viral vectors. Here, we encapsulate VEGF siRNA (siVEGF) in bioreducible lipidoid nanoparticles and examine whether these nanocomplexes can reduce intravitreal neovascularization in a rodent model of oxygen-induced retinopathy (OIR). Firstly, we constructed siVEGF-nanoparticles (NPs) and transfected human umbilical vein endothelial cells, which caused significantly reduced expression of VEGF, compared to exposure to siVEGF in solution. Secondly, we compared the effect of intravitreal siVEGF-NPs and an anti-VEGF drug (ranibizumab) on retinal vascular development and VEGF mRNA/protein expression in the retinas of a rat model of OIR. Compared to a non-functional lipid vehicle control group, the level of VEGF mRNA and protein was significantly lower in the siVEGF-NP group (p < 0.01), but the level of VEGF mRNA was not significantly lower in the ranibizumab group. Anatomically, the number of retinal neovascular endothelial nuclei that had protruded through the internal limiting membrane and the number of areas of non-perfusion of the retina were both significantly lower in the siVEGF-NP group and the ranibizumab group than in the OIR group (p < 0.01). Our results demonstrate that bioreducible lipidoid nanoparticles conveying VEGF siRNA can effectively inhibit retinal neovascularization in a rodent model of OIR, and reduce the expression of VEGF mRNA and protein. This novel treatment modality could have profound implications for treating retinal angiogenic diseases.

Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles

AbstractDeveloping safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).

Protein and mRNA Delivery Enabled by Cholesteryl-Based Biodegradable Lipidoid Nanoparticles.

Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).

Combinatorial Library of Cyclic Benzylidene Acetal-Containing pH-Responsive Lipidoid Nanoparticles for Intracellular mRNA Delivery.

Lipidoid nanoparticles have been demonstrated to be effective for intracellular delivery of small molecule drugs, proteins, and nucleic acids. Stimuli-responsive lipidoid nanoparticles are able to further improve delivery efficacy and reduce carrier-induced toxicity. Our group previously developed reduction and photoresponsive combinatorial libraries of lipidoid nanoparticles for small molecule and biologics delivery. Herein, we describe the synthesis, characterization, and intracellular mRNA delivery application of a new library of pH-responsive lipidoid nanoparticles. The acid-degradable cyclic benzylidene acetal-containing cationic lipidoids (R-O16CBA) were synthesized through a multistep reaction and characterized by NMR and MS. The acid-triggered degradation of lipidoids was studied using NMR, MS, DLS, and TEM. The results revealed that the R-O16CBA lipidoid can be completely degraded at pH 5. The R-O16CBA lipidoid nanoparticles were then fabricated with different formulations of DOPE and cholesterol and tested in vitro for intracellular mRNA delivery.

Combinatorial Library of Light-Cleavable Lipidoid Nanoparticles for Intracellular Drug Delivery.

Synthetic lipid-like molecules (lipidoids) are superior for intracellular delivery of various bioactive cargos. Through incorporating stimuli-responsive linkers, lipidoid nanoparticle-based delivery systems with triggered-release features can be constructed. Enhanced delivery performances have been achieved using disulfide bond-containing bioreducible lipidoids. Herein, we further expand the stimuli-responsive combinatorial lipidoids library by integrating the photocleavable o-nitrobenzyl moiety into the hydrophobic tail of the lipidoids. The structures of these novel lipidoids were confirmed by NMR and MS. The nanoparticles were fabricated through self-assembly procedures, and their photoresponsive behaviors were examined. Light-regulated cargo release and following functionality restoration indicated the potential of the newly developed lipidoid nanoparticles for spatiotemporal delivery.

Protein Delivery: Intracellular Delivery of His‐Tagged Genome‐Editing Proteins Enabled by Nitrilotriacetic Acid–Containing Lipidoid Nanoparticles (Adv. Healthcare Mater. 6/2019)

In article number 1800996, Qiaobing Xu and co-workers report a new type of non-cationic lipidoid nanoparticle for His-tagged protein delivery. Active lipidoids are synthesized by conjugating nitrilotriacetic acid with hydrophobic tails and nanoparticles are formulated in the presence of helper lipids through self-assembly. The newly developed lipidoid nanoparticles are capable of delivering genome-editing proteins (Cre recombinase and CRISPR/Cas9 ribonucleoprotein) into mammalian cells.

Lipids and Polymers Mediated CRISPR/Cas9 Gene Editing

CRISPR (the clustered, regularly interspaced, short palindromic repeat)/Cas9 nuclease system is the most commonly used method for gene editing, with the advantages of simple operation, high efficiency and high specificity, and has been used in various animals and crops. In this article, we review the latest development in the delivery technology of CRISPR/Cas9 based on lipids and polymers. We discuss the comparative advantages of commercial liposomes, new cationic lipidoid nanoparticles and hybrid liposomes as vectors for the delivery of genes encoding Cas9 and sgRNA, as well as many successful examples of polymer nanoparticles or polymer hybrid nanocarriers. We also introduce research ideas for the construction of non-viral vectors to better modify the structure of lipids and polymers, or to combine several biomaterials in order to better suit the CRISPR/Cas9 delivery. Furthermore, we consider the limitations of the non-viral carriers suitable for the delivery of the CRISPR/Cas9 system, and propose to overcome these obstacles through developing novel gene editing delivery vectors for clinical research.

Lipidoid iron oxide nanoparticles are a platform for nucleic acid delivery to the liver

Targeted delivery of antisense drugs is a promising technology which can provide a platform for the development of highly effective therapeuticals against a broad range of diseases. Insufficient stability of RNA in biological media coupled with hydrophilicity that prevents the molecule from penetrating cell membranes considerably limit RNA application in clinical practice. The aim of this work was to design a system for antisense drug delivery to liver hepatocytes using lipidoid magnetic nanoparticles (LNP). Nanocubes (NC) with average sizes of 16 and 27 nm were synthesized through decomposition of iron (III) oleate under high temperature conditions and functionalized with a cationic lipidoid С12-200. Magnetic NC demonstrated good MR-contrasting properties. Biodistribution of LNP was studied in vivo in BALB/c mice using the MR scanner. Additionally, liver sections obtained from the mice were subjected to histological examination. Nanoparticles of smaller size did not have a cytotoxic effect on HepG2 and Huh7 cell lines, whereas for larger NC, IC50 was 21.5 μg/ml and 126 μg/ml for HepG2 and Huh7 cells, respectively. Smaller particles tended to accumulate in hepatocytes. Bigger NC mainly accumulated in the spleen but also ended up in liver macrophages. This fact can be explained by a bigger hydrodynamic size of nanoparticles with a bigger magnetic core. Particles with smaller cores are a more effective platform for the delivery of antisense drugs to hepatocytes.

Lipidoid iron oxide nanoparticles are a platform for nucleic acid delivery to the liver

Адресная доставка антисмысловых препаратов является перспективной технологией, на основе которой возможна разработка высокоэффективных лекарственных средств для терапии широкого спектра заболеваний. Однако недостаточная стабильность РНК в биологических средах и гидрофильность, ограничивающая проникновение через клеточные мембраны, существенно сужают их использование в клинической практике. Целью исследования была разработка средств доставки антисмысловых препаратов в гепатоциты печени с помощью липидоподобных магнитных наночастиц (ЛНЧ). Кубические магнитные наночастицы (НЧ) со средними размерами 16 и 27 нм синтезировали методом высокотемпературного разложения прекурсора — олеата железа (III) и химически модифицировали формуляцией, включающей катионный липидоид С12-200. Магнитные НЧ обладают хорошими МРТ-контрастными свойствами, биораспределение ЛНЧ исследовали in vivo на линейных мышах BALB/c с помощью МР-томографа. С этой же целью провели последующее гистологическое исследование срезов печени. Наночастицы меньшего размера не продемонстрировали цитотоксического действия по отношению к клеточным линиям HepG2 и Huh7, а для НЧ кубической формы большего размера IC составила 21,5 мкг/мл для HepG2 и 126 мкг/мл для Huh7. Выявлено, что НЧ меньшего размера аккумулируются преимущественно в гепатоцитах печени, а НЧ большего размера — в селезенке, в печени же они накапливаются главным образом в макрофагах. Такая разница может быть вызвана большим гидродинамическим размером НЧ, которые имеют больший размер магнитного ядра. Образец с ядром меньшего размера является наиболее эффективной платформой для доставки антисмысловых препаратов в гепатоциты.