Effective induction of anti-tumor immunity using p5 HER-2/neu derived peptide encapsulated in fusogenic DOTAP cationic liposomes co-administrated with CpG-ODN

Mansourian, Mercedeh; Badiee, Ali; Jalali, Seyed Amir; Shariat, Sheida; Yazdani, Mona; Amin, Mohamdreza; Jaafari, Mahmoud Reza

doi:10.1016/j.imlet.2014.07.008

Cited by 62 publications

(47 citation statements)

References 35 publications

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“…1,4,24,51 Therefore, despite advancements in biologically derived delivery systems we presently lack a simple and easily controllable system for macromolecular delivery to the cellular interior. Toward realizing this goal, synthetic molecules that promote membrane fusion have been developed, including fusogenic lipids 34,55 and surfactants 16,30 as well as fusogenic peptides. 42,44,58 While these approaches have been demonstrated to drive delivery of diverse macromolecules including whole genes 11,12 and proteins, 27 they require large doses of fusion-promoting molecules, making them inefficient in comparison to biological fusion systems, and often leading to toxicity and immunogenicity in vivo.…”

Section: Introductionmentioning

confidence: 99%

Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm

et al. 2017

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INTRODUCTION From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. OBJECTIVES Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. METHODS We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. RESULTS Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. CONCLUSIONS Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and molecular cues associated with target cells.

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Section: Introductionmentioning

confidence: 99%

Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm

et al. 2017

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“…4) Similar to siRNA delivery, polypeptide-DOTAP systems are important in the studies of cancer therapies and therefore various formulations containing DOTAP have been developed. 4,5) Regarding the molecular mechanisms through with polypeptide-loaded cationic NPs function as cancer vaccines, E7 peptide-DOTAP NPs have been shown to induce the production of reactive oxygen species (ROS) in bone marrow-derived dendritic cells. 6) In addition, cationic liposomes containing DOTAP or stearylamine have been suggested to induce ROS and concomitant apoptosis and/or toxicity in cells.…”

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confidence: 99%

Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells

Yun

Bae

Ahn

2016

Biological & Pharmaceutical Bulletin

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These effects were dependent on the lipid concentration, surface density of cationic lipids, and particle size of NPs. However, neutral NPs consisting of 1,2-dioleoyl-3-phosphocholine did not elicit the effective ROS generation or cell death regardless of the lipid concentration and particle size. The present study suggests that DOTAP-and DOTMA-NPs are able to induce cancer cell death through production of ROS in the absence of any therapeutic cancer reagents. These results also provide a rational background for the design of delivery systems using cationic lipid-based NP formulations.

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“…Each of the three lipids has its unique function. DOTAP [47], as a cationic lipid, may strengthen the association between the lipid layer and the negatively charged PLGA core via electrostatic attraction. The carboxylic acid groups on DSPE-PEG(2000)COOH serve as the ligand for conjugating nicotine epitope.…”

Section: Discussionmentioning

confidence: 99%

The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

Smith

Frazier

et al. 2016

Biomaterials

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Owing to the urgent need for more effective treatment against nicotine addiction, a hybrid nanoparticle-based nicotine vaccine (NanoNiccine) was developed in this study. NanoNiccine was composed of a poly(lactide-co-glycolide) acid (PLGA) core, keyhole limpet hemocyanin (KLH) as an adjuvant protein enclosed within the PLGA core, a lipid layer, and nicotine haptens conjugated to the outer surface of the lipid layer. In contrast to the traditional nicotine vaccine, NanoNiccine is not a nicotine-protein conjugate vaccine. Instead, the nicotine hapten and protein are separately located in the nanostructure to minimize antibody production towards KLH. The cellular uptake study demonstrated that NanoNiccine was ideal for internalization and processing by dendritic cells (DCs). Mice immunized with NanoNiccine produced much lower IgG level against KLH as compared to that immunized with the traditional nicotine-KLH (Nic-KLH) vaccine. In addition, NanoNiccine achieved up to a 400% higher titer of anti-nicotine IgG than the positive control, Nic-KLH. Additionally, the Th1/Th2 index of NanoNiccine suggested that the immune response induced by NanoNiccine was antibody response dominant. Furthermore, NanoNiccine was found to be safe in mice.

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Effective induction of anti-tumor immunity using p5 HER-2/neu derived peptide encapsulated in fusogenic DOTAP cationic liposomes co-administrated with CpG-ODN

Cited by 62 publications

References 35 publications

Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm

Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm

Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells

The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

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