Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model

Markov, Oleg V.; Миронова, Н. Л.; Shmendel, Elena V.; Serikov, Roman N.; Морозова, Н. Г.; Маслов, М. А.; Vlassov, Valentin V.; Zenkova, Marina A.

doi:10.1016/j.jconrel.2015.06.028

Cited by 68 publications

(38 citation statements)

References 68 publications

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“…Non-viral vectors such as lipids, lipid-like materials, polymer or hybrid systems are widely studied for delivery of mRNA vaccines, which have low unwanted immune responses in contrast to the viral systems including adeno- associated viruses, lentiviruses and the Sendai virus ( Giacca and Zacchigna, 2012 ; Midoux and Pichon, 2015 ; Hajj and Whitehead, 2017 ). Liposomes (LPs) are the most appealing and commonly used non-viral carriers of mRNA vaccines ( Markov et al, 2015 ; Kranz et al, 2016 ; Persano et al, 2017 ; Verbeke et al, 2017 ). The mRNA loaded LPs namely RNA-LPX for cancer immunotherapy have been in phase I dose-escalation trial ( Kranz et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

et al. 2018

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Liposomes (LPs) as commonly used mRNA delivery systems remain to be rationally designed and optimized to ameliorate the antigen expression of mRNA vaccine in dendritic cells (DCs). In this study, we synthesized mannose-cholesterol conjugates (MPn-CHs) by click reaction using different PEG units (PEG100, PEG1000, and PEG2000) as linker molecules. MPn-CHs were fully characterized and subsequently used to prepare DC-targeting liposomes (MPn-LPs) by a thin-film dispersion method. MPn-LPs loaded with mRNA (MPn-LPX) were finally prepared by a simple self-assembly method. MPn-LPX displayed bigger diameter (about 135 nm) and lower zeta potential (about 40 mV) compared to MPn-LPs. The in vitro transfection experiment on DC2.4 cells demonstrated that the PEG length of mannose derivatives had significant effect on the expression of GFP-encoding mRNA. MP1000-LPX containing MP1000-CH can achieve the highest transfection efficiency (52.09 ± 4.85%), which was significantly superior to the commercial transfection reagent Lipo 3K (11.47 ± 2.31%). The optimal DC-targeting MP1000-LPX showed an average size of 132.93 ± 4.93 nm and zeta potential of 37.93 ± 2.95 mV with nearly spherical shape. Moreover, MP1000-LPX can protect mRNA against degradation in serum with high efficacy. The uptake study indicated that MP1000-LPX enhanced mRNA expression mainly through the over-expressing mannose receptor (CD206) on the surface of DCs. In conclusion, mannose modified LPs might be a potential DC-targeting delivery system for mRNA vaccine after rational design and deserve further study on the in vivo delivery profile and anti-tumor efficacy.

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Section: Introductionmentioning

confidence: 99%

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

et al. 2018

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“…Liposomes represent versatile nanoparticles that have been approved for the delivery of chemotherapeutics in Kaposi's sarcoma and allow for the co-formulation of adjuvants 27,28 . They can be targeted to glycan-binding proteins (GBPs) including CLRs or sialic acidbinding immunoglobulin-like lectins (Siglecs) expressed on immune cells using glycans or glycomimetic ligands [29][30][31] .…”

Section: Introductionmentioning

confidence: 99%

A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

Wamhoff

Bellmann

Bachem

et al. 2018

Preprint

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Langerhans cells are a subset of dendritic cells residing in the epidermis of the human skin. As such, they are key mediators of immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, the induction of protective T cell immunity by these vaccines requires the efficient and specific delivery of both tumor-associated antigens and adjuvants.Langerhans cells uniquely express Langerin (CD207), an endocytic C-type lectin receptor. Here, we report the discovery of a specific, glycomimetic Langerin ligand employing a heparin-inspired design strategy that integrated NMR spectroscopy and molecular docking. The conjugation of these glycomimetics to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. This delivery platform provides superior versatility and scalability over antibody-based approaches and thus addresses current limitations of dendritic cell-based immunotherapies.

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“…Therefore, NAs are delivered into DCs using physical methods (e.g., electroporation [ 16 , 26 - 28 ] or sonoporation [ 29 , 30 ]); viral systems (adenoviruses, adeno-associated viruses, retroviruses, lentiviruses, Vaccinia virus, etc. [ 31 - 38 ]); and nonviral systems (polycationic polymers [ 31 , 39 - 41 ] and cationic liposomes [ 28 , 42 - 45 ]).…”

Section: Preparation Of Dc-based Antitumor Vaccinesmentioning

confidence: 99%

Antitumor Vaccines Based on Dendritic Cells: From Experiments using Animal Tumor Models to Clinical Trials

et al. 2017

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The routine methods used to treat oncological diseases have a number of drawbacks, including non-specific action and severe side effects for patients. Furthermore, tumor diseases are associated with a suppression of the immune system that often leads to the inefficiency of standard treatment methods. The development of novel immunotherapeutic approaches having specific antitumor action and that activate the immune system is of crucial importance. Vaccines based on dendritic cells (DCs) loaded with tumor antigens ex vivo that can activate antitumor cytotoxic T-cell responses stand out among different antitumor immunotherapeutic approaches. This review is focused on analyzing different methods of DC-based vaccine preparation and current research in antitumor DC-based vaccines using animal tumor models and in clinical trials.

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Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model

Cited by 68 publications

References 68 publications

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

Antitumor Vaccines Based on Dendritic Cells: From Experiments using Animal Tumor Models to Clinical Trials

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