Co-Delivery of Astaxanthin and siTGF-ß1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy.

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor ß1 (siTGF-ß1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-ß1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-ß1, delivered by ASNPs, significantly silenced the expression of TGF-ß1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-ß1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

Elimination of intracellular Ca2+ overload by BAPTA­AM liposome nanoparticles: A promising treatment for acute pancreatitis.

Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2­bis(2­aminophenoxy)ethane­N,N,N',N'­tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA­AM), a cell­permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra­ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA­AM­loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF­α, IL­6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.

Plant-Derived Vesicles: A New Era for Anti-Cancer Drug Delivery and Cancer Treatment.

Lipid-structured vesicles have been applied for drug delivery system for over 50 years. Based on their origin, lipid-structured vesicles are divided into two main categories, namely synthetic lipid vesicles (SLNVEs) and vesicles of mammalian origin (MDVEs). Although SLNVEs can stably transport anti-cancer drugs, their biocompatibility is poor and degradation of exogenous substances is a potential risk. Unlike SLNVEs, MDVEs have excellent biocompatibility but are limited by a lack of stability and a risk of contamination by dangerous pathogens from donor cells. Since the first discovery of plant-derived vesicles (PDVEs) in carrot cell supernatants in 1967, emerging evidence has shown that PDVEs integrate the advantages of both SLNVEs and MDVEs. Notably, 55 years of dedicated research has indicated that PDVEs are an ideal candidate vesicle for drug preparation, transport, and disease treatment. The current review systematically focuses on the role of PDVEs in cancer therapy and in particular compares the properties of PDVEs with those of conventional lipid vesicles, summarizes the preparation methods and quality control of PDVEs, and discusses the application of PDVEs in delivering anti-cancer drugs and their underlying molecular mechanisms for cancer therapy. Finally, the challenges and future perspectives of PDVEs for the development of novel therapeutic strategies against cancer are discussed.

[Preparation of Mycobacterium tuberculosis EsxV lipid nanoparticles subunit vaccine and its immunological characteristics].

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.

A liposomal carbohydrate vaccine, adjuvanted with an NKT cell agonist, induces rapid and enhanced immune responses and antibody class switching.

BACKGROUND: Congenital disorders of glycosylation (CDGs) are genetic diseases caused by gene defects in glycan biosynthesis pathways, and there is an increasing number of patients diagnosed with CDGs. Because CDGs show many different clinical symptoms, their accurate clinical diagnosis is challenging. Recently, we have shown that liposome nanoparticles bearing the ALG1-CDG and PMM2-CDG biomarkers (a tetrasaccharide: Neu5Ac-α2,6-Gal-ß1,4-GlcNAc-ß1,4-GlcNAc) stimulate a moderate immune response, while the generated antibodies show relatively weak affinity maturation. Thus, mature antibodies with class switching to IgG are desired to develop high-affinity antibodies that may be applied in medical applications. RESULTS: In the present study, a liposome-based vaccine platform carrying a chemoenzymatic synthesized phytanyl-linked tetrasaccharide biomarker was optimized. The liposome nanoparticles were constructed by dioleoylphosphatidylcholine (DOPC) to improve the stability and immunogenicity of the vaccine, and adjuvanted with the NKT cell agonist PBS57 to generate high level of IgG antibodies. The results indicated that the reformulated liposomal vaccine stimulated a stronger immune response, and PBS57 successfully induce an antibody class switch to IgG. Further analyses of IgG antibodies elicited by liposome vaccines suggested their specific binding to tetrasaccharide biomarkers, which were mainly IgG2b isotypes. CONCLUSIONS: Immunization with a liposome vaccine carrying a carbohydrate antigen and PBS57 stimulates high titers of CDG biomarker-specific IgG antibodies, thereby showing great potential as a platform to develop rapid diagnostic methods for ALG1-CDG and PMM2-CDG.

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats.

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

Matairesinol Nanoparticles Restore Chemosensitivity and Suppress Colorectal Cancer Progression in Preclinical Models: Role of Lipid Metabolism Reprogramming.

Oncogenic-driven lipogenic metabolism is a common hallmark of colorectal cancer (CRC) progression. Therefore, there is an urgent need to develop novel therapeutic strategies for metabolic reprogramming. Herein, the metabolic profiles in the plasma between CRC patients and paired healthy controls were compared using metabolomics assays. Matairesinol downregulation was evident in CRC patients, and matairesinol supplementation significantly represses CRC tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS) colitis-associated CRC mice. Matairesinol rewired lipid metabolism to improve the therapeutic efficacy in CRC by inducing mitochondrial damage and oxidative damage and blunting ATP production. Finally, matairesinol-loaded liposomes significantly promoted the enhanced antitumor activity of 5-Fu/leucovorin combined with oxaliplatin (FOLFOX) in CDX and PDX mouse models by restoring chemosensitivity to the FOLFOX regimen. Collectively our findings highlight matairesinol-mediated lipid metabolism reprogramming as a novel druggable strategy to restore CRC chemosensitivity, and this nanoenabled approach for matairesinol will improve the chemotherapeutic efficacy with good biosafety.

Preparation of Mycobacterium tuberculosis EsxV lipid nanoparticles subunit vaccine and its immunological characteristics / 生物工程学报

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.

Injectable Immunotherapeutic Hydrogel Containing RNA-Loaded Lipid Nanoparticles Reshapes Tumor Microenvironment for Pancreatic Cancer Therapy.

Pancreatic cancer immunotherapy is becoming a promising strategy for improving the survival rate of postsurgical patients. However, the low response rate to immunotherapy suggests a low number of antigen-specific T cells and a high number of immunosuppressive tumor-associated macrophages in the pancreatic tumor microenvironment. Herein, we developed an in situ injectable thermosensitive chitosan hydrogel loaded with lipid-immune regulatory factor 5 (IRF5) mRNA/C-C chemokine ligand 5 (CCL5) siRNA (LPR) nanoparticle complexes (LPR@CHG) that reprogram the antitumoral immune niche. The LPR@CHG hydrogel upregulates IRF5 and downregulates CCL5 secretion, which contribute to a significant increase in M1 phenotype macrophages. Tumor growth is controlled by effective M1 phenotype macrophage that initiate T cell-mediated immune responses. Overall, the LPR@CHG hydrogel is expected to be a meaningful immunotherapy platform that can reshape the immunosuppressive tumor microenvironment and improve the efficacy of current pancreatic immunotherapies while minimizing systemic toxicity.

Nanoparticle-Delivered microRNA-153-3p Alleviates Myocardial Infarction-Induced Myocardial Injury in a Rat Model.

Although microRNA-153-3p (miR-153-3p) has been demonstrated to confer protective roles in ischemia/reperfusion injury, its potential role in myocardial infarction (MI) remains undefined. Small-molecule modifiers and nanoparticles loaded with microRNAs (miRNAs) have emerged as potential therapeutic reagents for MI treatment. In this study, we prepared liposome nanoparticles, hyaluronic acid (HA)-cationic liposomes (CLPs) complex, for the delivery of miR-153-3p and delineated the mechanistic actions of miR-153-3p modified by nHA-CLPs in MI-induced injury. Our data suggested that nHA-CLPs-loaded miR-153-3p protected cardiomyocytes against MI-induced cardiomyocyte apoptosis and myocardial injury. miR-153-3p was bioinformatically predicted and experimentally verified to bind to Krüppel-like factor 5 (KLF5) 3'UTR and negatively regulate its expression. Hypoxia was adopted to stimulate MI-induced injury to cardiomyocytes in vitro, in which miR-153-3p presented anti-apoptotic potential. However, restoration of KLF5 reversed this anti-apoptotic effect of miR-153-3p. Furthermore, KLF5 was demonstrated to be an activator of the NF-κB pathway. KLF5 enhanced cardiomyocyte apoptosis and inflammation under hypoxic conditions through NF-κB pathway activation, while nHA-CLPs-loaded miR-153-3p suppressed inflammation by blocking the NF-κB pathway. Collectively, our findings suggested the cardioprotective role of miR-153-3p against MI and the successful delivery of miR-153-3p by nHA-CLPs. The identification of KLF5-mediated activation of NF-κB pathway as an apoptotic and inflammatory mechanism aids in better understanding of the biology of MI and development of novel therapeutic strategies for MI.

Liposome Nanoparticles as a Novel Drug Delivery System for Therapeutic and Diagnostic Applications.

Liposome nanoparticles (LNPs), as a promising platform in drug delivery, combine the advantages of both liposomes and inorganic/organic nanoparticles into a single system. Both liposomes and nanoparticles have demonstrated optimized drug efficacy in the clinic. LNPs are proven to be multifunctional systems and thus utilized in various research applications (e.g., spatiotemporal control of drug release, hyperthermia, photothermal therapy, and biological imaging). The type of nanoparticles involved in LNPs largely affects the features of LNPs. Besides, diverse nanoparticles enable liposomes to overcome the defects such as poor stability, few functions, and rapid elimination from blood circulation. In this review, multiple nanoparticles materials and further prepared LNPs as well as their structure, physicochemical properties, manipulation and the latest applications in biomedical field are introduced. Future directions in advancing of LNPs are also discussed in the end.

[Preparation, Characterization and Pharmacokinetic Study of Arginine Deiminase Lipid Nanoparticles].

OBJECTIVE: To prepare and characterize D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) modified arginine deiminase (ADI) sulfobutyl-ß-Cyclodextrin liposome nanoparticles (ATCL), and to investigate the pharmacokinetic characteristics of ATCL in animals. METHODS: The reverse evaporation method was used to prepare ATCL, and the particle size and Zeta potential of ATCL were measured. Thiosemicarbazone-diacetylmonooxime colorimetric method was used to measure the activity of ADI. After intravenous administration, blood was drawn at set intervals of time and the enzyme activity in the plasma was measured. Enzyme activity-time curve was drawn subsequently and Debris Assessment Software (DAS) 2.1.1 was used to analyze the pharmacokinetic characteristics. RESULTS: The particle size and the potential of ATCL were (216.1±13.6) nm and (-19.4±2.1) mV, respectively. The optimal temperature and optimal pH for the catalytic reaction of ADI and ATCL were the same, both being 37 ℃ and pH6.5. Results of the analysis showed that the AUC (0-168 h), MRT (0-168 h), C max, T max, and t 1/2 of ATCL were 3.99, 2.56, 1.58, 3.2, and 9.88 times those of free ADI, respectively. Compared with ADI, the bioavailability of ATCL increased by 298.54%. CONCLUSION: ATCL prepared in the study can effectively improve the enzyme activity and bioavailability of ADI in Sprague-Dawley rats.

Ruthenium(II)-curcumin liposome nanoparticles: Synthesis, characterization, and their effects against cervical cancer.

Ruthenium complexes have increased the scope for improvement in current cancer treatment by replacing platinum-based drugs. However, to reduce metal-associated toxicity, a biocompatible flavonoid, such as curcumin, is indispensable, as it offers uncompensated therapeutic benefits through formation of complexes. In this study, we synthesized metal-based flavonoid complexes using ruthenium(II) and curcumin by adopting a convenient reflux reaction, represented as Ru-Cur complexes. These complexes were thoroughly characterized using 1H, 13C NMR, XPS, FT-IR, and UV-vis spectroscopy. As curcumin is sparingly soluble in water and has poor chemical stability, we loaded Ru-Cur complexes into liposomes and further formed nanoparticles (NPs) using the thin layer evaporation method. These were named Ru-Cur loaded liposome nanoparticles (RCLNPs). The effects of RCLNPs on cell proliferation was investigated using human cervical cancer cell lines (HeLa). These RCLNPs exhibited significant cytotoxicity in HeLa cells. The anticancer properties of RCLNPs were studied using reactive oxygen species (ROS), LDH, and MTT assays as well as live-dead staining. Nuclear damage studies of RCLNPs were performed in HeLa cells using the Hoechst staining assay.

Multifunctional Liposomes Enable Active Targeting and Twinfilin 1 Silencing to Reverse Paclitaxel Resistance in Brain Metastatic Breast Cancer.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for breast cancer, but PTX resistance often occurs in metastatic breast cancer. In addition, due to the poor targeting of chemotherapeutic drugs and the presence of the blood-brain barrier (BBB), it is hard to effectively treat brain metastatic breast cancer using paclitaxel. Thus, it is urgent to develop an effective drug delivery system for the treatment of brain metastatic breast cancer. The current study found that TWF1 gene, an epithelial-mesenchymal transition-associated gene, was overexpressed in brain metastatic breast cancer (231-BR) cells and was associated with the PTX resistance of 231-BR cells. Knockdown of TWF1 by small interference RNA (siRNA) in 231-BR cells could effectively increase the sensitivity of brain metastatic breast cancer cells to paclitaxel. Then, a liposome-based drug delivery system was developed for PTX delivery across BBB, enhancing PTX sensitivity and brain metastases targeting via BRBP1 peptide modification. The results showed that BRBP1-modified liposomes could effectively cross the BBB, specifically accumulate in brain metastases, and effectively interfere TWF1 gene expression in vitro and in vivo, and thus they enhanced proliferation inhibition, cell cycle arrest, and apoptosis induction, thereby inhibiting the formation and growth of brain metastases. In summary, our results indicated that BRBP1-modified and PTX- and TWF1 siRNA-loaded liposomes have the potential for the treatment of brain metastatic breast cancer, which lays the foundation for the development of a new targeted drug delivery system.

Enhanced gene expression by a novel designed leucine zipper endosomolytic peptide.

An endosomal trap is a major barrier in gene therapy. We have designed an endosomolytic peptide based on the leucine zipper sequence and characterized it both structurally and functionally. The results illustrated that leucine zipper endosomolytic peptide (LZEP) exhibited appreciable hemolysis of human red blood cells (hRBCs) at pH 5.0, but negligible hemolysis at pH 7.4. Calcein release experiment indicated that only at pH 5.0 but not at pH 7.4, LZEP was able to permeabilize hRBCs. LZEP revealed significant self-assembly as well as peptide induced α-helical structure at pH 5.0. Unlike at pH 5.0, LZEP failed to self-assemble and showed a random coil structure at pH 7.4. Transfection data depicted that lipoplexes modified with LZEP resulted in significantly higher gene expression as compared to lipoplexes without LZEP. Interestingly, the transfection efficacy of LZEP modified lipid nanoparticles reached the levels of Lipofectamine 2000 (LF 2000), without any cellular toxicity as observed by MTT assay. The results suggest a novel approach for designing endosomolytic peptides by employing the leucine zipper sequence and simultaneously the designed peptides could be utilized for enhancing gene delivery into mammalian cells.

The effect of different organic solvents in liposome properties produced in a periodic disturbance mixer: Transcutol®, a potential organic solvent replacement.

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development.

Synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery, and theranostic applications.

Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into the active site without any side effects. Herein, ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl) bis (2-methoxy-4,1-phenylene) diacetate acetyl curcumin (AC)-loaded poly(lactic-co-glycolic acid) (PLGA) core/shell liposome nanoparticles (ACPCSLNPs) were prepared using an electron spray method under an applied electric field, which facilitated the uniform formation of nano-sized liposome nanoparticles (LNPs). Then, kinetically controlled and sustained drug release profiles were investigated using the as-prepared ACPCSLNPs. Moreover, the inner polymeric core could not only induce the generation of electrostatic interactions between the polymer and drug molecules but could also affect the prominent repulsions between the polar head groups of lipids and the nonpolar drug molecules. As a result, the sustained maximum release of the drug molecules (~48.5%) into the system was observed over a long period (~4 days). Furthermore, cell cytotoxicity studies were conducted in a human cervical cancer cell line (HeLa) and a healthy human dermal fibroblast cell line (HDFa) by employing all AC loaded LNPs along with free drugs. Multicolor cell imaging was also observed in HeLa cells using ACPCSLNPs. Notably, more curcumin was released from the ACPCSLNPs than AC due to the presence of polar group attractions and polar-polar interactions between the lipid head groups and curcumin since curcumin is more soluble than AC in aqueous medium. In addition, the predictions of the release kinetic patterns were also investigated thoroughly using the exponential-based Korsmeyer-Peppas (K-P) and Higuchi models for drug-loaded LNPs and PLGA NPs, respectively.

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs.

BACKGROUND: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses. METHODS: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals. RESULTS: Liposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs. CONCLUSION: Overall, our study shows great promise for using liposome and MSU adjuvant- based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.

MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma.

MiR-101, an important tumor-suppressive microRNA (miRNA) in hepatocellular carcinoma (HCC), has been affirmed significantly downregulated in HCC and participated in promoting apoptosis, decreasing proliferation and invasiveness of HCC cells, as well as increasing sensitivity of chemotherapeutic drug. However, miR-101-based combination therapies with doxorubicin (DOX) are not reported yet. Recently, nanomaterials-based approaches, especially liposome formulations, have been approved for clinical use and seem to provide a great opportunity to codeliver therapeutic agents for cancer therapy. In this study, we have successfully prepared liposome (L) nanoparticles to efficiently deliver miR-101 and DOX to HCC cells simultaneously. The effects of codelivery system miR-101/doxorubicin liposome (miR-101/DOX-L) on tumor malignant phenotypes of HCC cells were evaluated through analyzing cell proliferation, colony formation, cell migration, cell invasion, cell apoptosis assay, and the expression of related genes. In subcutaneous xenografts developed by HCC cells, the inhibition of tumor growth was analyzed through gross morphology, growth curve, proliferation marker Ki-67, apoptosis signals, and the expression of related genes. These experiments demonstrated that miR-101/DOX-L inhibited tumor properties of liver cancer cells in vitro and in vivo through targeting correlative genes by combinatory role of miR-101 and DOX. In conclusion, our results indicated that liposome nanoparticle is a reliable delivery strategy to codeliver miR-101 and DOX simultaneously, and miR-101- and DOX-based combination therapy can result in significant synergetic antitumor effects in vivo and vitro.

Effects of liposome nanoparticles of hydrazinocurcumin on cell proliferation, apoptosis, invasion, and migration in MDA-MB-231 cells / 中草药

Objective: To investigate the effects of liposome nanoparticles of hydrazinocurcumin (HC-NPs) on cells proliferation, apoptosis, invasion, and migration in human breast cancer MDA-MB-231 cells. Methods: Liposome HC-NPs were prepared by film-sonication method and then were used to treat human breast cancer MDA-MB-231 cells. The treated cell survival was analyzed by MTT; Morphological changes were detected by Liu staining; The cell cycle and apoptosis were investigated by FCM assay; Then invasion and migration of the cells were analyzed by Transwell. Moreover, the expression of proteins correlated to cell cycle arrest, apoptosis, invasion, and migration were detected by Western blotting. Results: The cell proliferation was inhibited by HC-NPs, the cells became round in shape, and the cells were arrested in G 2/M phase, the ratio of apoptosis was increased (P<0.01), the cells invasion and migration were restrained. The expression of p-STAT3, CyclinD1, Survivin, Bcl-2, and MMP-9 were down-regulated, while the expression of Bax was up-regulated. Conclusion: The effects of HC-NPs on the suppression of cell proliferation, invasion, and migration, and induction of cells apoptosis may be related to the inhibition of STAT3 activation.