Cationic liposomal lipids: From gene carriers to cell signaling

Lonez, Caroline; Vandenbranden, Michel; Ruysschaert, Jean Marie

doi:10.1016/j.plipres.2008.03.002

Cited by 190 publications

(141 citation statements)

References 101 publications

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“…Despite their promise in in vitro trials, most of these systems are ineffective in vivo due to the toxicity of the cationic moieties and their non-specific interactions with non-target cells limit their widespread use. High-inflammatory responses to these systems have also restricted their use as gene delivery systems in vivo (Lonez et al, 2008). Therefore, attempts to reduce or mask the cationic moieties have been reported to reduce the adverse effects of these systems.…”

Section: Introductionmentioning

confidence: 99%

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

et al. 2014

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Background: RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue. Objective: Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing. Methods: In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy. Results: PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks. Conclusion: Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.

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Section: Introductionmentioning

confidence: 99%

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

et al. 2014

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“…Complexing CpG into liposomes has been shown to further augment the stimulatory capacity of the adjuvant and increase cell-mediated immunity (16)(17)(18)(19). In addition to acting as a delivery vehicle, liposomes protect the components from degradation and facilitate Ag uptake by APCs, leading to enhanced Ag recognition and vaccine-specific immune responses (20)(21)(22)(23). Several liposome-based vaccines are currently in clinical trials; however, the cellular targets of these formulations and mechanisms of immune induction are yet to be defined (24).…”

mentioning

confidence: 99%

Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

Neeland

Elhay²,

Nathanielsz³

et al. 2014

The Journal of Immunology

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Liposomal vaccine formulations incorporating stimulants that target innate immune receptors have been shown to significantly increase vaccine immunity. Following vaccination, innate cell populations respond to immune stimuli, phagocytose and process Ag, and migrate from the injection site, via the afferent lymphatic vessels, into the local lymph node. In this study, the signals received in the periphery promote and sculpt the adaptive immune response. Effector lymphocytes then leave the lymph node via the efferent lymphatic vessel to perform their systemic function. We have directly cannulated the ovine lymphatic vessels to detail the in vivo innate and adaptive immune responses occurring in the local draining lymphatic network following vaccination with a liposome-based delivery system incorporating CpG. We show that CpG induces the rapid recruitment of neutrophils, enhances dendritic cell–associated Ag transport, and influences the maturation of innate cells entering the afferent lymph. This translated into an extended period of lymph node shutdown, the induction of IFN-γ–positive T cells, and enhanced production of Ag-specific Abs. Taken together, the results of this study quantify the real-time in vivo kinetics of the immune response in a large animal model after vaccination of a dose comparable to that administered to humans. This study details enhancement of numerous immune mechanisms that provide an explanation for the immunogenic function of CpG when employed as an adjuvant within vaccines.

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“…The enhanced effect may depend on the electrostatic interactions between cationic liposomes and negatively charged cell membranes, which in turn could improve the uptake and delivery of liposomes by DCs. 45 Analysis of cytokine production from the spleen revealed a significant downregulation for IFN-γ for all liposome formulations compared to the sham-treated group. There was furthermore a tendency for lower levels of IL-5, IL-4, and IL-10 compared to sham-treated mice and free OVA for the cationic liposomes, although these were not significant.…”

mentioning

confidence: 92%

Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

Aliu¹,

Rask²,

Brimnes³

et al. 2017

IJN

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Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers’ ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.

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Cationic liposomal lipids: From gene carriers to cell signaling

Cited by 190 publications

References 101 publications

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

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