Cationic Liposomes Research Articles

Combining Liposomal Photocatalysts with Whole‐Cell Catalysts for One‐pot Photobiocatalysis

AbstractCooperative photobiocatalytic processes have seen extensive potentials for the synthesis of both bulk and fine chemicals owing to their versatility, eco‐friendliness, and cost‐effectiveness. Nevertheless, developing a universal and effective synthetic strategy compatible with both catalytic systems remains challenging. In this study, we explored cationic liposomes as biocompatible photocatalyst encapsulation systems and combined them with bacteria overexpressing enzymes for two‐step and three‐step cascade reactions. Specifically, the water‐soluble photocatalyst anthraquinone‐2‐sulfonate (AQS), which can oxidize benzyl alcohol, is encapsulated within the core of cationic liposomes composed of dioleoyl‐3‐trimethylammonium propane (DOTAP) and the helper lipid cholesterol. The positive charge on the liposome surface enabled electrostatic interactions with the negative charges on the membrane of Escherichia coli cells. Bacterial cells overexpressing various enzymes, such as Candida antarctica lipase B (CalB) and benzaldehyde lyase (BAL), and coated with liposomes enabled the production of added value compounds through cascade reactions with excellent production. These cascades involve CalB‐catalyzed hydrolysis, BAL‐catalyzed condensation, and AQS‐driven photo‐oxidation reactions. Therefore, the strategy offers more possibilities of combining photocatalysis with biocatalysis for recoverability, enhanced mass transfer, and enhanced compatibility in both industrial biotechnology and synthetic chemistry.

Rabies virus-mimicking liposomes for targeted gene therapy in Alzheimer’s disease

RNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system, coupled with the inherent instability of nucleic acids within biological conditions, poses formidable challenges in advancing effective gene delivery strategies. In this study, we designed and prepared a virus-mimic non-viral gene vector, rabies virus glycoprotein (RVG29)-decorated liposome (f(Lipo)-RVG29), to deliver small interfering RNAs to the brain. Alzheimer’s disease (AD) was chosen as a model of neurodegenerative disease in this context, and b-site APP cleaving enzyme silencing siRNA (siBACE1) was used. The developed liposomal delivery system has a particle size of under 80 nm with a spherical shape, positive zeta potential, and the ability to protect siRNA against nucleases. In vitro studies demonstrate that functionalizing the cationic liposome by the RVG29 targeting ligand significantly enhances the effectiveness of gene delivery and silencing. Examination through ex vivo imaging illustrates an increased deposition of fluorescent-labeled f(Lipo)-RVG29 within brain tissue after 12 h post application. Additionally, the in vivo delivery of f(Lipo)-RVG29 carrying siRNA has substantially suppressed BACE1 expression at both mRNA and protein levels within the brain tissue. Our results suggest that the developed non-viral vector could be a promising gene carrier system combining the synergistic effect of virus-mimic RVG29 ligand with bioinspired liposome that imitates the natural lipid bilayers of cell membranes for brain-targeted RNAi therapeutics.

Cationic Lipid Derived from a Basic Amino Acid: Design and Synthesis

One of the major challenges in gene therapy is the efficient and safe introduction of nucleic acids into eukaryotic cells. This process requires overcoming various biological barriers and navigating complex pathways to reach target cells and achieve their biological function. To address this obstacle, numerous transfection methods have been developed, including physical techniques and the use of genetic vectors, both viral and non-viral. However, to date, no transfection method is 100% safe and efficient. Within the spectrum of non-viral genetic vectors, cationic liposomes formed by cationic lipids stand out for their ability to protect and deliver therapeutic NA. These liposomes offer greater biocompatibility and lower immunogenicity compared to viral vectors, although they still do not match the efficiency of viral delivery systems. Consequently, ongoing research focuses on synthesizing a wide variety of cationic lipids in the search for compounds that provide high transfection efficiency with minimal cytotoxicity. This study aimed to design and synthesize a novel cationic lipid (CholCadLys) derived from natural cellular molecules for transferring genetic material to eukaryotic cells. The lipid was synthesized using cholesteryl chloroformate for the hydrophobic region, cadaverine as a linker, and lysine for the polar region, connected by carbamate and amide bonds, respectively. Identification was confirmed through thin-layer chromatography, purification through preparative chromatography, and characterization via infrared spectroscopy and mass spectrometry. The synthesis yielded a 60% success rate, with stable nanoliposomes averaging 76 nm in diameter. Liposomes were formed using this CL and commercial neutral lipids, characterized by transmission electron microscopy and Nanoparticle Tracking Analysis. These liposomes, combined with plasmid DNA, formed lipoplexes used to transfect Hek-293 FT cells, achieving up to 40% transfection efficiency without cytotoxicity in the mixture of CholCadLys and CholCad. This novel CL demonstrates potential as an efficient, safe, and cost-effective gene transfer system, facilitating further development in gene therapy.

Brief Comparison of the Efficacy of Cationic and Anionic Liposomes as Nonviral Delivery Systems.

In recent decades, the development and application of nonviral vectors, such as liposomes and lipidic nanoparticles, for gene therapy and drug delivery have seen substantial progress. The interest in the physicochemical properties and structures of the complexes liposome/DNA and liposome/RNA is due to their potential to substitute viruses as carriers of drugs or genetic material into cells with minimal cytotoxicity, which could lead to their use in gene therapy. Initially, cationic liposomes were utilized as nonviral DNA delivery vectors; subsequently, different molecules, such as polymers, were incorporated to enhance transfection efficiency. Additionally, liposome/protein complexes have been developed as nonviral vectors for the treatment of diseases. The most relevant internalization pathways of these vectors and the few transfection results obtained using targeted and nontargeted liposomes are discussed below. The high cytotoxicity of cationic liposomes represents a significant challenge for the development of gene therapy and drug delivery. Anionic liposomes offer a promising alternative to address the limitations of conventional cationic liposomes, including immune response, short circulation time, and low toxicity. This review will discuss the advantages of cationic liposomes and the novel anionic liposome-based systems that have emerged as a result. The advent of novel designs and manufacturing techniques has facilitated the development of innovative systems, designated as lipid nanoparticles (LNPs), which serve as highly efficacious regulators of the immune system.

Optimizing Transfection Efficiency of Spermine Polar Head Cholesterol-Based Cationic Lipids with Amino Acid Linker.

In this work, a series of spermine polar head cholesterol-based cationic lipids with various amino acid spacers were synthesized and evaluated as non-viral gene delivery systems. The physicochemical properties of the resulting lipoplexes, formed from these lipids and DOPE, were assessed, including zeta-potential, DNA binding and DNA protection from serum. Transfection efficiency and cytotoxicity were examined under serum-free and 10-40 % serum-containing conditions. The results showed that the physicochemical properties of cationic lipids, both with and without amino acid spacers, were not significantly different. Cationic liposomes composed of lipid Sper-Ahx-Chol, which has a 6-aminohexanoic acid spacer, and DOPE exhibited greater transfection efficiency in HeLa cells compared to Lipofectamine3000, both in the absence and presence of 10-40 % serum. Additionally, lipid Sper-His-Chol with a histidine spacer and Sper-Ahx-Chol showed higher efficiency than Lipofectamine3000 against HEK293T under 40 % serum conditions. These results suggest that the incorporation of amino acids into the cationic lipids can significantly enhance their DNA delivery efficiency. Specifically, certain amino acid modifications improved transfection efficiency while maintaining low cytotoxicity. Our findings highlight the potential of amino acid-tailored cationic lipids as promising vectors for enhanced DNA delivery.

Cationic and ionizable amphiphiles based on di-hexadecyl ester of <I>L</I>-glutamic acid for liposomal transport of RNA

Various RNAs are among the most promising and actively developed therapeutic agents for the treatment of tumors, infectious diseases and a number of other pathologies associated with the dysfunction of specific genes. Some nanocarriers are used for the effective delivery of RNAs to target cells, including liposomes based on cationic and/or ionizable amphiphiles. Cationic amphiphiles contain a protonated amino group and exist as salts in an aqueous environment. Ionizable amphiphiles are a new generation of cationic lipids that exhibit reduced toxicity and immunogenicity and undergo ionization only in the acidic environment of the cell. In this work we developed a scheme for the preparation and carried out the synthesis of new cationic and ionizable amphiphiles based on natural amino acids (L-glutamic acid, glycine, beta-alanine, and gamma-aminobutyric acid). Cationic and ionizable liposomes were formed based on the obtained compounds, mixed with natural lipids (phosphatidylcholine and cholesterol), and their physicochemical characteristics (particle size, zeta potential, and storage stability) were determined. Average diameter of particles stable for 5–7 days did not exceed 100 nm. Zeta potential of cationic and ionizable liposomes was about 30 and 1 mV, respectively. The liposomal particles were used to form complexes with RNA molecules. Such RNA complexes were characterized by atomic force microscopy and their applicability for nucleic acid transport was determined.

Complexes of Anionic and Cationic Liposomes for Encapsulation of Bioactive Substances

Complexes of Anionic and Cationic Liposomes for Encapsulation of Bioactive Substances

NK cell membrane/MnO2 hybrid nanoparticle-adjuvanted intranasal vaccines synergistically boost protective immunity against H1N1 influenza infection

Intranasal vaccines hold a huge promise for preventing influenza infection, however, their development is compromised due to mucosal barriers and limited systemic and mucosal immunity. Herein, a novel biomimetic nano-adjuvant based on NK cell membrane (MNK)/MnO2 hybrid nanoparticles (NLipoMn) was developed for intranasal administration of H1N1 inactivated influenza vaccine (IIV). NK cell membrane, served as TLR4 agonist was fused with cationic liposomes encapsulating STING agonist MnO2 NPs (LipoMn) to yield NLipoMn, which inherited versatile characteristics to prolong the nasal retention of IIV. Encouragingly, CCL20 secretion was enhanced by NLipoMn-activated the TLR4/NF-κB pathway in mucosal endothelial cells, thereby promoting submucosal dendritic cells (DCs) recruitment for IIV uptake. Moreover, NLipoMn-IIV synergistically harnessed TLR4 and STING signaling pathway to augment STING activation though NLipoMn-activated the TLR4/NF-κB pathway, which demonstrated a superiority to elicit strong DCs maturation, CD8+ T cells activation, and high levels of antigen-specific IgG, antigen-specific IgA, cytokines secretion, resulting in a robust systemic and mucosal immune responses. Notably, intranasal immunization with NLipoMn-IIV elicited an effective immune protection against homologous and heterologous H1N1 influenza virus infection. This study provides a promising adjuvant candidate to develop needle-free intranasal vaccines that are active against influenza and other respiratory viral infection.

Targeted delivery of rhein via hyaluronic acid modified liposomes for suppression of growth and metastasis of breast cancer

Targeting and suppressing the malignant growth and metastasis of breast cancer has been challenging for years. Herein, a nanocarrier based on hyaluronic acid (HA)-modified cationic liposomes was developed for targeted delivery of rhein to achieve breast cancer therapy. The optimum HA-Lip-rhein had spherical and core-shell-like morphologies with an appropriate size of 189.7 ± 5.2 nm. Moreover, the HA-Lip-rhein exhibited higher cellular uptake in 4 T1 cells and enhanced cytotoxicity compared with unmodified liposomal rhein. Furthermore, in vitro cell migration and invasion inhibition assays showed that the HA-Lip-rhein exhibited superior inhibitory effects on breast cancer metastasis. HA-Lip-rhein improved the tumor targeting ability, anti-breast cancer activity, with good safety profile in the 4 T1 breast cancer-bearing mice compared with free rhein and Lip-rhein. The appearance of metastatic tumor nodules in the lungs and H&E staining of liver and lung organs confirmed that HA-Lip-rhein exerted strong antitumor efficacy and inhibited distant metastasis of breast cancer. Overall, the developed HA-Lip-rhein exhibited a good antitumor effect and suppression effect of distant metastasis, making it a novel and promising nanoplatform for further development.

Transdermal Delivery of Ultradeformable Cationic Liposomes Complexed with miR211-5p (UCL-211) Stabilizes BRAFV600E+ Melanocytic Nevi.

Small non-coding RNAs (e.g. siRNA, miRNA) are involved in a variety of melanocyte-associated skin conditions and act as drivers for alterations in gene expression within melanocytes. These molecular changes can potentially affect the cellular stability of melanocytes and promote their oncogenic transformation. Thus, small RNAs can be considered as therapeutic targets for these conditions, however, their topical delivery to the melanocytes through the epidermal barrier is challenging. We synthesized and extensively evaluated ultradeformable cationic liposome (UCLs) carriers complexed with synthetic microRNAs (miR211-5p; UCL-211) for transdermal delivery to melanocytes. UCL-211 complexes were characterized for their physicochemical properties, encapsulation efficiency, and deformability, which revealed a significant advantage over conventional liposomal carriers. Increased expression of miR211-5p stabilizes melanocytic nevi and keeps them in growth-arrested state. We did a comprehensive assessment of cellular delivery, and biological activity of the miR211-5p carried by UCL-211 in vitro and their permeation through the epidermis of intact skin using ex vivo human skin tissue explants. We also demonstrated, in vivo, that topical delivery of miR211-5p by UCL-211 stabilized BRAFV600E+ nevi melanocytes in a benign nevi state.

Evaluation of PLGA, lipid-PLGA hybrid nanoparticles, and cationic pH-sensitive liposomes as tuberculosis vaccine delivery systems in a Mycobacterium tuberculosis challenge mouse model – A comparison

Tuberculosis (TB) continues to pose a global threat for millennia, currently affecting over 2 billion people and causing 10.6 million new cases and 1.3 million deaths annually. The only existing vaccine, Mycobacterium Bovis Bacillus Calmette-Guérin (BCG), provides highly variable and inadequate protection in adults and adolescents. This study explores newly developed subunit tuberculosis vaccines that use a multistage protein fusion antigen Ag85b-ESAT6-Rv2034 (AER). The protection efficacy, as well as in vivo induced immune responses, were compared for five vaccines: BCG; AER-CpG/MPLA mix; poly(D,L-lactic-co-glycolic acid) (PLGA); lipid-PLGA hybrid nanoparticles (NPs); and cationic pH-sensitive liposomes (the latter three delivering AER together with CpG and MPLA). All vaccines, except the AER-adjuvant mix, induced protection in Mycobacterium tuberculosis (Mtb)-challenged C57/Bl6 mice as indicated by a significant reduction in bacterial burden in lungs and spleens of the animals. Four AER-based vaccines significantly increased the number of circulating multifunctional CD4+ and CD8+ T-cells producing IL-2, IFNγ, and TNFα, exhibiting a central memory phenotype. Furthermore, AER-based vaccines induced an increase in CD69+ B-cell counts as well as high antigen-specific antibody titers. Unexpectedly, none of the observed immune responses were associated with the bacterial burden outcome, such that the mechanism responsible for the observed vaccine-induced protection of these vaccines remains unclear. These findings suggest the existence of non-classical protective mechanisms for Mtb infection, which could, once identified, provide interesting targets for novel vaccines.

Biocompatible cationic 5-fluorouracil loaded elastic liposomes for ocular delivery: In vitro, ex vivo, and in vivo evaluation

5-fluorouracil (5-FU) is used to treat scleral and episcleral fibroblast proliferations (scarring process) in the eyes. Frequent washing of the conventional solution results in limited drug access to the eyes. Taguchi and central composite design (CCD) oriented optimized mucoadhesive cationic elastic liposomes were prepared and characterized. The optimized F-CEL8 (composed of 85 mg of dipalmitoyl-phosphatidylcholine, 15 mg of sodium cholate, 10 mg of 5-FU, 7 mg of ethanol, and 883 mg of buffer) and its gel were studied for in vitro and ex vivo drug release profiles as compared to the drug solution and the liposomes. In vitro hemolysis and Draize studies corroborated safety concerns. An in vivo pharmacokinetics study was studied in rats. Each mL of F-CEL8 contained dipalmitoyl-phosphatidylcholine (X1), sodium cholate, and ethanol to deliver 10 mg of 5-FU with optimal vesicle size, low polydispersity index (PDI), and high zeta potential (ZP). The %EE value of spherical F-CEL8 was quite high (82.3 ± 7.1 %) as compared to liposomes (∼53 %) due to the large volume of the inner aqueous chamber of vesicles. F-CEL8-gel exhibited relatively high viscosity for slow and sustained release for 24 h as compared to others. The percent permeation of 5-FU from the solution, F-CEL8, F-CEL8-gel, and the liposomes were found to be 28.6 ± 4.6 %, 69.6 ± 7.4 %, 76.89 ± 12.4 %, and 54.8 ± 5.3 %, respectively. All isotonic formulations did not exhibit hemolysis and irritation to the eyes. The gel illustrated the highest values of pharmacokinetics parameters as compared to the solution and the liposomes, which may be attributed to the maximum residence time achieved through electrostatic interaction (the vesicle internalization with the mucosal layer of eyes).

Mobilizing STING Pathway via a Cationic Liposome to Enhance Doxorubicin‐Induced Antitumor Immunity

AbstractThe efficacy of anthracycline, such as doxorubicin (DOX), is facilitated by cancer cell‐intrinsic type I interferon (IFN‐I) signaling through the induction of immune responses. However, weak and chronic IFN‐I responses from rounds of chemotherapy lead to resistance against DNA damage and acquired resistance to the therapy. An exogenous supply of IFN‐I can improve the chemotherapeutic responses. Herein, a library of cationic liposomes is developed for the optimization of 1, 2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) proportions to enhance the lysosome escape and tumor distribution of the stimulator of interferon genes (STING) agonist 2′,3′‐cyclic guanosine monophosphate‐adenosine monophosphate (cGAMP) and DOX. The cationic liposomes with 8% DOTAP release cGAMP into the cytoplasm and increase the concentration of DOX in the tumor by 1.5 times compared with the free drug. Upon accumulation at the tumor site, the optimized liposomes induce immunogenic cell death (ICD) and stimulate the STING signaling, thereby improving the production of endogenous IFN‐I and promoting dendritic cell maturation to mobilize T cell immunity. The tumor growth inhibition rate is 86%, and the median survival time is 1.6‐fold prolonged. This study offers a strategy to enhance the DOX‐induced immune response by activating the STING pathway to supply IFN‐I.

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.

Liposomal Nanoformulation-encapsulated Paclitaxel for Reducing Chemotherapy Side Effects in Lung Cancer Treatments: Recent Advances and Future Outlooks.

Paclitaxel is one notable chemotherapy drug that is used to treat a number of cancers, including lung cancer. Nevertheless, it has drawbacks such as toxicity, low solubility in water, and the emergence of multidrug resistance (MDR). This article reviews the use of liposomal formulations to improve paclitaxel administration and efficacy for lung cancer therapy. Paclitaxel's pharmacological characteristics can be improved by liposomes through increased solubility, extended circulation, passive tumor targeting through leaky vasculature, and decreased side effects. Recent developments in paclitaxel liposomal formulations, including as cationic liposomes, conventional liposomes, targeted liposomes with particular ligands, and liposome-loaded microorganisms, are outlined in this article. In comparison to free paclitaxel, these nanoformulations exhibit enhanced cytotoxicity, cellular uptake, apoptosis, tumor growth suppression, and anticancer effects in lung cancer cell lines and animal models. One efficient way to get around the drawbacks of paclitaxel is to alter its size, makeup, and surface characteristics. This will let the medication accumulate and penetrate tumors more easily, avoid multidrug resistance, and cause less systemic toxicity. The article explores clinical studies showcasing the safety and therapeutic efficacy of liposomal paclitaxel for individuals afflicted with lung cancer. In its entirety, the document provides an in-depth examination of the potential enhancement in paclitaxel's dispersion and anti-tumor impacts through the utilization of liposomal technology when addressing diverse manifestations of lung cancer.

Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis

Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.

An intranasal cationic liposomal polysaccharide vaccine elicits humoral immune responses against Streptococcus pneumoniae

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo+CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens.

A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.

Apoptosis induced by cationic liposome based on the mitochondrial signaling pathway in vitro

Apoptosis induced by cationic liposome based on the mitochondrial signaling pathway in vitro

Cationic Curcumin Nanocrystals Liposomes for Improved Oral Bioavailability: Formulation Development, Optimization, In Vitro and In Vivo Evaluation.

Curcumin, a naturally occurring poorly water-soluble polyphenol with a broad spectrum, is a typical BCS IV drug. The objective of this study was to develop curcumin nanocrystals liposomes with the aim of improving bioavailability. In this study, we prepared cationic curcumin nanocrystals with a particle size of only 29.42 nm; such a phenomenal range of particle sizes is very rare. Moreover, we summarized and evaluated the parameters of the nanocrystal preparation process, including methods, formulations, etc., and the rules we concluded can be generalized to other nanocrystal preparation processes. To counteract the instability of the nanocrystals in the digestive tract, cationic curcumin nanocrystals were loaded into negatively charged liposomes through gravitational force between different charges. Unexpectedly, chitosan oligosaccharide was found to promote the self-assembly process of curcumin nanocrystal liposomes. In vitro and in vivo experiments demonstrated that chitosan-modified curcumin nanocrystal liposomes exhibited enhanced resistance to enzyme barriers, mucus barriers, and cellular barriers, resulting in a 5.4-fold increase in bioavailability compared to crude powder formulations. It can be concluded that cationic nanocrystals liposomes represent an appropriate novel strategy for improving the dissolution rate and bioavailability of poorly soluble natural products such as curcumin.