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

Bros, Matthias; Nuhn, Lutz; Simon, Johanna; Moll, Lorna; Mailänder, Volker; Landfester, Katharina; Grabbe, Stephan

doi:10.3389/fimmu.2018.01760

Cited by 65 publications

(76 citation statements)

References 124 publications

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“…e protein corona plays a fundamental role in the biodistribution of NPs, and in particular, in the recognition by the MPS, especially through the adsorption of opsonins such as immunoglobulin G (IgG), coagulation proteins (i.e., fibrinogen), or complement components, which are believed to promote recognition by specific receptors on macrophage and phagocytosis [29,47,49]. On the contrary, dysopsonins, such as apolipoprotein J (clusterin) and albumin, were reported to reduce the adsorption of opsonins on the surface of NPs conferring "stealth properties" [47,50].…”

Section: Protein Corona and Macrophage Eliminationmentioning

confidence: 99%

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Baboci

Capolla

Cintio

et al. 2020

Journal of Oncology

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e development of nanostructures for therapeutic purpose is rapidly growing, following the results obtained in vivo in animal models and in the clinical trials. Unfortunately, the potential therapeutic efficacy is not completely exploited, yet. is is mainly due to the fast clearance of the nanostructures in the body. Nanoparticles and the liver have a unique interaction because the liver represents one of the major barriers for drug delivery. is interaction becomes even more relevant and complex when the drug delivery strategies employing nanostructures are proposed for the therapy of liver diseases, such as hepatocellular carcinoma (HCC). In this case, the selective delivery of therapeutic nanoparticles to the tumor microenvironment collides with the tendency of nanostructures to be quickly eliminated by the organ. e design of a new therapeutic approach based on nanoparticles to treat HCC has to particularly take into consideration passive and active mechanisms to avoid or delay liver elimination and to specifically address cancer cells or the cancer microenvironment. is review will analyze the different aspects concerning the dual role of the liver, both as an organ carrying out a clearance activity for the nanostructures and as target for therapeutic strategies for HCC treatment.

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Section: Protein Corona and Macrophage Eliminationmentioning

confidence: 99%

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Baboci

Capolla

Cintio

et al. 2020

Journal of Oncology

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“…One of the biggest limitations for nanoparticle-based therapies is the formation of a protein corona (PC) on the nanoparticle surface and its effect on their biological performance. Therefore, it is fundamental to include systematic studies on NP-PC complexes and to define the biological identity of the final nano-formulation in the field of nano-therapy [107,108]. These studies will be useful in order to predict the physicochemical changes, such as protein absorption, of the NPs that could affect NP-based immunotherapies causing "immune blinding" or immune reactivity.…”

Section: Future Perspectivesmentioning

confidence: 99%

Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

Mikelez-Alonso

Aires

Cortajarena

2020

IJMS

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Immunotherapy has become a promising cancer therapy, improving the prognosis of patients with many different types of cancer and offering the possibility for long-term cancer remission. Nevertheless, some patients do not respond to these treatments and immunotherapy has shown some limitations, such as immune system resistance or limited bioavailability of the drug. Therefore, new strategies that include the use of nanoparticles (NPs) are emerging to enhance the efficacy of immunotherapies. NPs present very different pharmacokinetic and pharmacodynamic properties compared with free drugs and enable the use of lower doses of immune-stimulating molecules, minimizing their side effects. However, NPs face issues concerning stability in physiological conditions, protein corona (PC) formation, and accumulation in the target tissue. PC formation changes the physicochemical and biological properties of the NPs and in consequence their therapeutic effect. This review summarizes the recent advances in the study of the effects of PC formation in NP-based immunotherapy. PC formation has complex effects on immunotherapy since it can diminish (“immune blinding”) or enhance the immune response in an uncontrolled manner (“immune reactivity”). Here, future perspectives of the field including the latest advances towards the use of personalized protein corona in cancer immunotherapy are also discussed.

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“…Панели 0, 30, 60 мин: флуоресценция фагоцитированных липосом, «гейтированная» по субпопуляциям лейкоцитов после инкубаций 0, 30, 60 мин (добавлен тушитель флуоресценции адсорбированных клетками липосом; желтые зоны -клетки с неполностью затушенной флуоресценцией липосом на поверхности). TMB-PC липосомы следующих составов: только из ePC (образец L) и МТХ-липосомы ePC-MTXDG 9 : 1 (образец L-MTXDG), ePC-MTXDG-PI 8 : 1 : 1 (образец L-MTXDG-PI), ePC-MTXDG-CMGPE 8 : 1 : 1 (образец L-MTXDG-CMG), ePC-MTXDG-GM 1 [24]. Нами установлено [26,27], что компонент C3b на поверхности липосом без MTXDG не детектируется при иммуноблотинге, т.е.…”

Section: результаты и обсуждениеunclassified

“…Эти данные и различный уровень поглощения клетками МТХ-липосом и липосом без пролекарства (при инкубации 60 мин, рис. 4, кроме CMG-липосом) согласуются с данными [24] о поглощении липосом моноцитами через узнавание опсонинов на поверхности липидного бислоя.…”

Section: результаты и обсуждениеunclassified

“…Однако оказалось, что пегилирование, как и покрытие другими полимерами, не препятствует неспецифическому связыванию белков и может вызывать инфузионные реакции различной степени тяжести, вплоть до анафилактического шока, связанные с активацией системы комплемента (СК) [19][20][21][22]. Белковая корона -комплексный слой белков и липопротеинов -образуется в течение нескольких секунд при контакте наночастиц, в том числе липосом, с плазмой крови [23,24]. Опсонизация наноносителя белками СК способствует его распознаванию рецепторами иммунокомпетентных клеток.…”

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

Cited by 65 publications

References 124 publications

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

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

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