Cationic Carriers Research Articles

Stable Polymer-Lipid Hybrid Nanoparticles Based on mcl-Polyhydroxyalkanoate and Cationic Liposomes for mRNA Delivery.

Background/Objectives: The development of polymer-lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core-shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in terms of their physical stability and biocompatibility. Natural polymers such as polyhydroxyalkanoate (PHA) can be used as a matrix for the PLNs' preparation. Methods: In this study, we first obtained stable cationic hybrid PLNs using a cationic liposome (CL) composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and the hydrophobic polymer mcl-PHA, which was produced by the soil bacterium Pseudomonas helmantisensis P1. Results: The new polymer-lipid carriers effectively encapsulated and delivered model mRNA-eGFP (enhanced green fluorescent protein mRNA) to BHK-21 cells. We then evaluated the role of mcl-PHA in increasing the stability of cationic PLNs in ionic solutions using dynamic light scattering data, electrophoretic mobility, and transmission electron microscopy techniques. Conclusions: The results showed that increasing the concentration of PBS (phosphate buffered saline) led to a decrease in the stability of the CLs. At high concentrations of PBS, the CLs aggregate. In contrast, the presence of isotonic PBS did not result in the aggregation of PLNs, and the particles remained stable for 120 h when stored at +4 °C. The obtained results show that PLNs hold promise for further in vivo studies on nucleic acid delivery.

Combinatorial Synthesis of Alkyl Chain-Capped Poly(β-Amino Ester)s for Effective siRNA Delivery.

Poly (β-amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza-Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa-Luc cells. Specifically, PA8-C6 and PA8-C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end-capping groups. A pKa range of ≈6.2-6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co-formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.

516LBA (PB-516) LBA Posters: Potassium/sodium cation carriers robustly upregulate CD20 antigen by targeting MYC and synergize with anti-CD20 immunotherapies to eliminate malignant B cells

516LBA (PB-516) LBA Posters: Potassium/sodium cation carriers robustly upregulate CD20 antigen by targeting MYC and synergize with anti-CD20 immunotherapies to eliminate malignant B cells

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Ultra-sensitive detection of cadmium and lead in water using crown ether gel electromembrane extraction coupled with miniaturized electrochemical system

This study presents the development of an electrochemical technique combined with gel electromembrane extraction (G-EME) for the simultaneous detection of cadmium and lead in environmental water samples. Crown ether (18C6) was added to the gel as a complexing agent and cationic carrier. The electrochemical responses were evaluated using differential pulse anodic stripping voltammetry (DPASV) across various pH levels and deposition times. The most sensitive response (acetate buffer pH 4, deposition time 90 s) was selected for the development of the G-EME process. By applying a 30 V electrical potential across the gel membrane containing 1 % (w/v) of 18C6 for 10 min, positively charged Cd2+ and Pb2+ ions migrated from the donor phase (pH 5.0) through the 18C6@gel membrane (pH 5.0) into the acceptor phase (pH 5.0). This resulted in a linear range from 0.3 to 5 µg/L for Cd2+ and 0.5 to 5 µg/L for Pb2+, with detection limits of 0.10 µg/L and 0.19 µg/L, respectively— up to 120 times more sensitive than direct electrochemical measurements. Furthermore, the proposed technique maintained selectivity for cadmium and lead, despite the presence of other potential heavy metal ions in the environment.

Florfenicol core–shell composite nanogels as oral administration for efficient treatment of bacterial enteritis

To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core–shell composite nanogels in this study. The florfenicol core–shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, –22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core–shell composite nanogels were successfully prepared. Florfenicol core–shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core–shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core–shell composite nanogels. Therefore, the prepared florfenicol core–shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.

A genetically encoded fluorescent protein sensor for mitochondrial membrane damage detection

Mitochondria are essential cellular organelles; detecting mitochondrial damage is crucial in cellular biology and toxicology. Compared with existing chemical probe detection methods, genetically encoded fluorescent protein sensors can directly indicate cellular and molecular events without involving exogenous reagents. In this study, we introduced a molecular sensor system, MMD-Sensor, for monitoring mitochondrial membrane damage. The sensor consists of two molecular modules. Module I is a fusion structure of the mitochondrial localization sequence (MLS), AIF cleavage site sequence (CSS), nuclear localization sequence (NLS), N-terminus of mNeonGreen and mCherry. Module II is a fusion structure of the C-terminus of mNeonGreen, NLS sequence, and mtagBFP2. Under normal condition, Module I is constrained in the inner mitochondrial membrane anchored by MLS, while Module II is restricted to the nucleus by its NLS fusion component. If the mitochondrial membrane is damaged, CSS is cut from the inner membrane, causing Module I to shift into the nucleus guided by the NLS fusion component. After Module I enters the nucleus, the N- and C-terminus of mNeonGreen meet each other and rebuild its intact 3D structure through fragment complementation and thus generates green fluorescence in the nucleus. Dynamic migration of red fluorescence from mitochondria to the nucleus and generation of green fluorescence in the nucleus indicate mitochondrial membrane damage. Using the MMD-Sensor, mitochondrial membrane damage induced by various reagents, such as uncoupling agents, ATP synthase inhibitors, monovalent cationic carriers, and ROS, in HeLa and 293T cells are directly observed and evaluated.

Abstract 1344: Improvement of the anti-tumor activity of NK cells and the efficacy of anti-CD20 monoclonal antibodies in the therapy of B cell-derived malignancies

Abstract Resistance of tumor cells to immunotherapy with monoclonal antibodies (mAbs) often relies on the reduced level of the antigen targeted by the particular mAb. We have therefore screened for the compounds able to upregulate selected antigens on the surface of lymphoma/leukemia cells, to minimize the possibility of resistance acquired by the tumor cells. We have found that members of a specific class of antibiotics, known as cation carriers, namely salinomycin (SAL), monensin (MON), narasin, and nigericin exhibit great CD20 antigen-upregulating abilities. A variety of Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL) cell lines as well as patients-derived primary malignant cells, such as DLBCL and chronic lymphocytic leukemia (CLL) cells exhibited upregulation of surface CD20 upon the treatment with SAL and MON at concentrations as low as 250nM and 50 nM, respectively. As a consequence, these compounds appeared to be beneficial for the therapy of lymphoma/leukemia with anti-CD20 mAbs, both in vitro and in animal models.Moreover, the proteomics analysis revealed that besides CD20, cation carriers upregulated a number of different proteins on the surface of tumor cells, including proteins implicated in the interaction with immune cells. These included ICAM1, HLA-A/B/C, CD155, CD80, CD86 and ULBP2/5/6. Particularly important appears to be the upregulation of antigens interacting with the activating receptors on NK cells, helping them to overcome the inhibitory signals and stimulate the lysis of tumor cells. Thus, the results of proteomics analysis explained why SAL- or MON-pretreated tumor cells were efficiently eliminated by NK cells, even in the absence of therapeutic mAb. In light of our discoveries, it seems reasonable to consider the cation carriers as promising drug candidates for the improvement of NK cell anti-tumor activity and potential treatment of B-cell non-Hodgkin lymphoma patients, in combination with anti-CD20 mAbs.Funding: National Science Centre (NCN, Poland), grants 2019/35/B/NZ5/01445 and 2020/39/B/NZ6/03513. Citation Format: Abdessamad Zerrouqi, Aleksandra Zdanowicz, Anna Torun, Andrzej Ciechanowicz, Bhaskar Pradhan, Grzegorz Rymkiewicz, Dimitar Efremov, Beata Pyrzynska. Improvement of the anti-tumor activity of NK cells and the efficacy of anti-CD20 monoclonal antibodies in the therapy of B cell-derived malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1344.

Non-Metal Ion Storage in Zinc-Organic Batteries.

Zinc-organic batteries (ZOBs) are receiving widespread attention as up-and-coming energy-storage systems due to their sustainability, operational safety and low cost. Charge carrier is one of the critical factors affecting the redox kinetics and electrochemical performances of ZOBs. Compared with conventional large-sized and sluggish Zn2+ storage, non-metallic charge carriers with small hydrated size and light weight show accelerated interfacial dehydration and fast reaction kinetics, enabling superior electrochemical metrics for ZOBs. Thus, it is valuable and ongoing works to build better ZOBs with non-metallic ion storage. In this review, versatile non-metallic cationic (H+, NH4 +) and anionic (Cl-, OH-, CF3SO3 -, SO4 2-) charge carriers of ZOBs are first categorized with a brief comparison of their respective physicochemical properties and chemical interactions with redox-active organic materials. Furthermore, this work highlights the implementation effectiveness of non-metallic ions in ZOBs, giving insights into the impact of ion types on the metrics (capacity, rate capability, operation voltage, and cycle life) of organic cathodes. Finally, the challenges and perspectives of non-metal-ion-based ZOBs are outlined to guild the future development of next-generation energy communities.

Improving rechargeable magnesium batteries through dual cation co-intercalation strategy

The development of competitive rechargeable Mg batteries is hindered by the poor mobility of divalent Mg ions in cathode host materials. In this work, we explore the dual cation co-intercalation strategy to mitigate the sluggishness of Mg2+ in model TiS2 material. The strategy involves pairing Mg2+ with Li+ or Na+ in dual-salt electrolytes in order to exploit the faster mobility of the latter with the aim to reach better electrochemical performance. A combination of experiments and theoretical calculations details the charge storage and redox mechanism of co-intercalating cationic charge carriers. Comparative evaluation reveals that the redox activity of Mg2+ can be improved significantly with the help of the dual cation co-intercalation strategy, although the ionic radius of the accompanying monovalent ion plays a critical role on the viability of the strategy. More specifically, a significantly higher Mg2+ quantity intercalates with Li+ than with Na+ in TiS2. The reason being the absence of phase transition in the former case, which enables improved Mg2+ storage. Our results highlight dual cation co-intercalation strategy as an alternative approach to improve the electrochemical performance of rechargeable Mg batteries by opening the pathway to a rich playground of advanced cathode materials for multivalent battery applications.

ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for prostate cancer treatment.

Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.

The photosensitizer system based on cationic COF carrier with the loading tetraminoporphyrin and its combined antibacterial effect

The 2D covalent organic framework COFTGTp was synthesized and TAPP deposited on it via π–π interactions to form TAPP/COFTGTp. Excellent antibacterial effect against both Gram-positive and Gram-negative bacteria was achieved with good biosafety.

Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer.

Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress.

Oxidative stress and mitochondrial dysfunction play central roles in reduced oocyte quality and infertility in obese patients. Mitochondria-targeted treatments containing co-enzyme Q10 such as mitoquinone (MitoQ) can increase mitochondrial antioxidative capacity; however, their safety and efficiency when supplemented to oocytes under lipotoxic conditions have not been described. We tested the effect of different concentrations of MitoQ or its cationic carrier (TPP) (0, 0.1, 0.5, 1.0 μM each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 μM) against palmitic acid (PA)-induced lipotoxicity and mitochondrial dysfunction in oocytes. Exposure to MitoQ, or TPP only, at 1 μM significantly (P<0.05) reduced oocyte mitochondrial inner membrane potential (JC-1 staining) and resulted in reduced cleavage and blastocyst rates compared with solvent control. Lower concentrations of MitoQ or TPP had no effects on embryo development under control (PA-free) conditions. As expected, PA increased the levels of MMP and ROS in oocytes (CellROX staining) and reduced cleavage and blastocyst rates compared with the controls (P<0.05). These negative effects were ameliorated by 0.1 μM MitoQ. In contrast, 0.1 μM TPP alone had no protective effects. MitoQ also normalized the expression of HSP10 and TFAM, and partially normalized HSP60 in the produced blastocysts, indicating at least a partial alleviation of PA-induced mitochondrial stress. Oocyte exposure to MitoQ may disturb mitochondrial bioenergetic functions and developmental capacity due to a TPP-induced cationic overload. A fine-tuned concentration of MitoQ can protect against lipotoxicity-induced mitochondrial stress during IVM and restore developmental competence and embryo quality.

Construction of Multi‐Module RNA Nanoparticles Harboring miRNA, AIE, and CH6 Aptamer for Bone Targeting and Bone Anabolic Therapy

AbstractBone healing remains a major challenge in the treatment of osteoporosis. Effective strategies that simultaneously promote bone formation and inhibit bone resorption are crucial for the treatment of osteoporosis and associated bone defects. MicroRNA (miRNA)‐based approaches aim at simultaneously promoting bone formation and suppressing bone resorption and have therapeutic potential. However, the toxicity of cationic carriers and off‐target effects are two major challenges associated with miRNA delivery. This study establishes a bone‐targeting miRNA delivery system (CH6‐SNA‐26a) that integrates aggregation‐induced emission (AIE), a CH6 aptamer, and miRNAs into a single nanoplatform without any cationic carrier. In this system, an AIE molecule is coupled to miR‐26a to form a core–shell spherical nucleic acid (SNA‐26a). The CH6 aptamer is co‐assembled with the SNA to achieve specific miR‐26a delivery to the bone surface. This aptamer‐functionalized, non‐cationic miR‐26a delivery strategy (CH6‐SNA‐26a) enables both bone‐targeted delivery and high transfection efficiency, ultimately optimizing bone remodeling and calvarial bone healing in an osteoporosis mouse model while limiting adverse effects in non‐skeletal tissues. Mechanistically, the overexpression of CH6‐SNA‐26a in skeletal tissues promotes bone anabolic action by functionally targeting glycogen synthase kinase 3 beta in bone marrow mesenchymal stem cells and cellular communication network 2 in osteoclasts.

Electromembrane extraction based on a fabricated novel carrier-mediated gel membrane: Determination of fluoroquinolones residue in urine and wastewater samples

This study reports the fabrication and application of green material, pectin gel containing cationic carrier agent as a green membrane in electromembrane extraction of polar fluoroquinolones for the first time. In this study, apple pomace pectin gel has been used with a low esterification degree (29 %) containing cetyl tributyl ammonium bromide at a concentration lower than its critical micelle concentration as a cationic carrier and ion-pairing agent as a gel membrane for electromembrane extraction of polar fluoroquinolones, levofloxacin and ciprofloxacin from urine and wastewater samples successfully. To make a gel membrane, pectin is dissolved in hot water along with the ionic carrier cetyltrimethylammonium bromide, and a gel-like substance with the ability to be molded is obtained. The gel-like substance is molded in a warm state inside the Eppendorf microtube and after being placed in the refrigerator for hardening, the end of the microtube is cut and the gel membrane is ready to use. Under optimized conditions, the suggested method demonstrated low detection limits toward target analytes (0.003 and 0.025 ng/mL for levofloxacin and ciprofloxacin respectively), a wide linear dynamic range (0.02–1000 and 0.2–1000 ng/mL for levofloxacin and ciprofloxacin respectively), as well as high sample clean-up and proper precision (intra-day RSD 7.4–13.5 %).

Biomimetic noncationic lipid nanoparticles for mRNA delivery.

Although the tremendous progress has been made for mRNA delivery based on classical cationic carriers, the excess cationic charge density of lipids was necessary to compress mRNA through electrostatic interaction, and with it comes inevitably adverse events including the highly inflammatory and cytotoxic effects. How to develop the disruptive technologies to overcome cationic nature of lipids remains a major challenge for safe and efficient mRNA delivery. Here, we prepared noncationic thiourea lipids nanoparticles (NC-TNP) to compress mRNA by strong hydrogen bonds interaction between thiourea groups of NC-TNP and the phosphate groups of mRNA, abandoning the hidebound and traditional electrostatic force to construct mRNA-cationic lipids formulation. NC-TNP was a delivery system for mRNA with simple, convenient, and repeatable preparation technology and showed negligible inflammatory and cytotoxicity side effects. Furthermore, we found that NC-TNP could escape the recycling pathway to inhibit the egress of internalized nanoparticles from the intracellular compartment to the extracellular milieu which was a common fact in mRNA-LNP (lipid nanoparticles) formulation. Therefore, NC-TNP-encapsulated mRNA showed higher gene transfection efficiency in vitro and in vivo than mRNA-LNP formulation. Unexpectedly, NC-TNP showed spleen targeting delivery ability with higher accumulation ratio (spleen/liver), compared with traditional LNP. Spleen-targeting NC-TNP with mRNA exhibited high mRNA-encoded antigen expression in spleen and elicited robust immune responses. Overall, our work establishes a proof of concept for the construction of a noncationic system for mRNA delivery with good inflammatory safety profiles, high gene transfection efficiency, and spleen-targeting delivery to induce permanent and robust humoral and cell-mediated immunity for disease treatments.

Li, Na, K, Mg, Zn, Al, and Ca Anode Interface Chemistries Developed by Solid-State Electrolytes.

Solid-state batteries (SSBs) have received significant attention due to their high energy density, reversible cycle life, and safe operations relative to commercial Li-ion batteries using flammable liquid electrolytes. This review presents the fundamentals, structures, thermodynamics, chemistries, and electrochemical kinetics of desirable solid electrolyte interphase (SEI) required to meet the practical requirements of reversible anodes. Theoretical and experimental insights for metal nucleation, deposition, and stripping for the reversible cycling of metal anodes are provided. Ion transport mechanisms and state-of-the-art solid-state electrolytes (SEs) are discussed for realizing high-performance cells. The interface challenges and strategies are also concerned with the integration of SEs, anodes, and cathodes for large-scale SSBs in terms of physical/chemical contacts, space-charge layer, interdiffusion, lattice-mismatch, dendritic growth, chemical reactivity of SEI, current collectors, and thermal instability. The recent innovations for anode interface chemistries developed by SEs are highlighted with monovalent (lithium (Li+ ), sodium (Na+ ), potassium (K+ )) and multivalent (magnesium (Mg2+ ), zinc (Zn2+ ), aluminum (Al3+ ), calcium (Ca2+ )) cation carriers (i.e.,lithium-metal, lithium-sulfur, sodium-metal, potassium-ion, magnesium-ion, zinc-metal, aluminum-ion, and calcium-ion batteries) compared to those of liquid counterparts.

Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery.

The growing significance of messenger RNA (mRNA) therapeutics in diverse medical applications, such as cancer, infectious diseases, and genetic disorders, highlighted the need for efficient and safe delivery systems. Lipid nanoparticles (LNPs) have shown great promise for mRNA delivery, but challenges such as toxicity and immunogenicity still remain to be addressed. In this study, we aimed to compare the performance of polyplex nanomicelles, our original cationic polymer-based carrier, and LNPs in various aspects, including delivery efficiency, organ toxicity, muscle damage, immune reaction, and pain. Our results showed that nanomicelles (PEG-PAsp(DET)) and LNPs (SM-102) exhibited distinct characteristics, with the former demonstrating relatively sustained protein production and reduced inflammation, making them suitable for therapeutic purposes. On the other hand, LNPs displayed desirable properties for vaccines, such as rapid mRNA expression and potent immune response. Taken together, these results suggest the different potentials of nanomicelles and LNPs, supporting further optimization of mRNA delivery systems tailored for specific purposes.

Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a.

Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogenization and used them as non-viral carriers for the anti-adipogenic miRNA-27a. Cargo-free octadecylamine-containing NLCs and miRNA/cNLC complexes were characterized regarding particle size, size distributions, zeta potential, pH values, particle topography and morphology, and entrapment efficacy. Furthermore, the cytotoxicity and cellular uptake of the miRNA/cNLC complex in the 3T3-L1 cell line were investigated. The investigation of the biological effect of miRNA-27a on adipocyte development and an estimation of the accumulated Oil-Red-O (ORO) dye in lipid droplets in mature adipocytes were assessed with light microscopy and absorbance measurements. The obtained data show that cNLCs represent a suitable DDS for miRNAs, as miRNA/cNLC particles are rapidly formed through non-covalent complexation due to electrostatic interactions between both components. The miRNA-27a/cNLC complex induced an anti-adipogenic effect on miRNA-27a by reducing lipid droplet accumulation in mature adipocytes, indicating that this approach might be used as a new therapeutic strategy for miRNA mimic replacement therapies in the prevention or treatment of obesity and obesity-related disorders.