Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs

Francian, Alexandra; Mann, Kristine; Kullberg, Max

doi:10.2147/ijn.s138787

Cited by 22 publications

(23 citation statements)

References 34 publications

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“…In addition, both components may dissociate and cause unwanted side effects. On the one hand, uptake of an antigen in the absence of an adjuvant by endocytic/phagocytic APC, but also by tumor-promoted myeloid-derived suppressor cells and tumor-associated macrophages ( 13 ) may cause tumor immune tolerance. On the other hand, stimulation of APC by an adjuvant alone may promote autoimmune reactions ( 14 ).…”

Section: Nanovaccinesmentioning

confidence: 99%

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

et al. 2018

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Nanocarriers (NC) are very promising tools for cancer immunotherapy. Whereas conventional vaccines are based on the administration of an antigen and an adjuvant in an independent fashion, nanovaccines can facilitate cell-specific co-delivery of antigen and adjuvant. Furthermore, nanovaccines can be decorated on their surface with molecules that facilitate target-specific antigen delivery to certain antigen-presenting cell types or tumor cells. However, the target cell-specific uptake of nanovaccines is highly dependent on the modifications of the nanocarrier itself. One of these is the formation of a protein corona around NC after in vivo administration, which may potently affect cell-specific targeting and uptake of the NC. Understanding the formation and composition of the protein corona is, therefore, of major importance for the use of nanocarriers in vaccine approaches. This Mini Review will give a short overview of potential non-specific interactions of NC with body fluids or cell surfaces that need to be considered for the design of NC vaccines for immunotherapy of cancer.

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Section: Nanovaccinesmentioning

confidence: 99%

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

et al. 2018

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“…Immune stimulation, immune suppression and immune modulation have all been reported for nanomaterials [ 6 , 7 ] partly as a result of the formation of a protein corona made up of serum proteins [ 8 – 13 ]. Opsonisation of nanomaterials by serum proteins such as immunoglobulins and complement proteins results in rapid uptake into cells such as macrophages and dendritic cells [ 10 , 14 ]. Interactions with serum proteins may render nanomaterials antigenic and it has been suggested that functionalisation (e.g.…”

Section: Introductionmentioning

confidence: 99%

Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems

et al. 2018

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BackgroundRecent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations. Here we have conducted a preclinical evaluation of efavirenz SDN to assess their potential interaction with these systems. Platelet aggregation and activation, plasma coagulation, haemolysis, complement activation, T cell functionality and phenotype, monocyte derived macrophage functionality, and NK cell function were assessed in primary healthy volunteer samples treated with either aqueous efavirenz or efavirenz SDN.ResultsEfavirenz SDNs were shown not to interfere with any of the systems studied in terms of immunostimulation nor immunosuppression. Although efavirenz aqueous solution was shown to cause significant haemolysis ex vivo, efavirenz SDNs did not. No other interaction with haematological systems was observed. Efavirenz SDNs have been demonstrated to be immunologically and haematologically inert in the utilised assays.ConclusionsTaken collectively, along with the recent observation that lopinavir SDN formulations did not impact immunological responses, these data indicate that this type of nanoformulation does not elicit immunological consequences seen with other types of nanomaterial. The methodologies presented here provide a framework for pre-emptive preclinical characterisation of nanoparticle safety.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0349-y) contains supplementary material, which is available to authorized users.

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“…Применение цитометрии для исследования взаимодействий липосом с субпопуляциями лейкоцитов крови описано лишь в нескольких публикациях [39][40][41][42], причем в работах [41] и [42] липосомы инкубировали с выделенными нейтрофилами или мононуклеарами соответственно, а не с цельной кровью. ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ В [39] кровь инкубировали с «твердофазными» пегилированными липосомами в течение 3 ч, тогда как в [40] -5 ч, затем эритроциты лизировали в гипотоническом буфере и проводили FACS-анализ, детектируя суммарную флуоресценцию связанных и поглощенных клетками липосом.…”

Section: результаты и обсуждениеunclassified

Lipophilic prodrug of methotrexate in the membrane of liposomes promotes their uptake by human blood phagocytes

et al. 2020

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Previously, we showed that incorporation of methotrexate (MTX) in the form of a lipophilic prodrug (MTXDG) in 100-nm lipid bilayer liposomes of egg phosphatidylcholine can allow one to reduce toxicity and improve the antitumor efficiency of MTX in a mouse model of T-cell leukemic lymphoma. However, in our hemocompatibility tests in vitro, MTX liposomes caused complement (C) activation, obviously due to binding on the liposome surface and fragmentation of the C3 complement factor. In this work, we studied the interactions of MTX liposomes carrying stabilizing molecules phosphatidylinositol (PI), ganglioside GM1, or a lipid conjugate of N-carboxymethylated oligoglycine (CMG) in the bilayer with subpopulations of human blood leukocytes. Liposomes labeled with BODIPY-phosphatidylcholine were incubated with whole blood (30 min and 1 h, 37C), blood cells were lysed with a hypotonic buffer, and the fluorescence of the liposomes bound but not internalized by the leukocytes was quenched by crystal violet. Cell suspensions were analyzed by flow cytometry. Incorporation of MTXDG dramatically enhanced the phagocytosis of liposomes of any composition by monocytes. Neutrophils consumed much less of the liposomes. Lymphocytes did not accumulate liposomes. The introduction of PI into MTX liposomes practically did not affect the specific consumption of liposomes by monocytes, while CMG was likely to increase the consumption rate regardless of the presence of MTXDG. The GM1 ganglioside presumably shielded MTX liposomes from phagocytosis by one of the monocyte populations and increased the efficiency of monocyte uptake by another population, probably one expressing C3b-binding receptors (C3b was detected on liposomes after incubation with blood plasma). MTX liposomes were shown to have different effects on TNF- production by activated leukocytes, depending on the structure of the stabilizing molecule.

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Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs

Cited by 22 publications

References 34 publications

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems

Lipophilic prodrug of methotrexate in the membrane of liposomes promotes their uptake by human blood phagocytes

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