Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

Colino, Clara I.; Lanao, José M.; Gutiérrez-Millán, Carmen

doi:10.3389/fimmu.2020.00218

Cited by 104 publications

(65 citation statements)

References 144 publications

(182 reference statements)

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“…However, such tailored drug-delivery systems have not yet advanced to clinical studies. 230,231 Galectin-3, a β-galactoside-binding lectin predominantly expressed in macrophages, mediates important inflammatory functions and is known to exert profibrogenic effects in HSCs. 232 Although promising results have been achieved with the galectin-3 inhibitor GR-MD-02 in preclinical murine models, 233 it did not alleviate fibrosis in a phase 2 clinical trial in NASH patients.…”

Section: Therapeutic Approaches For Targeting Macrophages In Liver DImentioning

confidence: 99%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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Macrophages, which are key cellular components of the liver, have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases. Upon liver injury, resident Kupffer cells (KCs) sense disturbances in homeostasis, interact with hepatic cell populations and release chemokines to recruit circulating leukocytes, including monocytes, which subsequently differentiate into monocyte-derived macrophages (MoMϕs) in the liver. Both KCs and MoMϕs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases. The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases. In this review, we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease.

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Section: Therapeutic Approaches For Targeting Macrophages In Liver DImentioning

confidence: 99%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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“…Notably, for each given type of NP, a big difference in uptake between differentially polarized macrophages was observed: those with a regulatory phenotype (M2 type) showed more than 40% higher uptake than proinflammatory macrophages (M1 type). In agreement, KCs were found to internalize relatively large NPs (˃200 nm Ø) in vivo [ 85 ]. An interesting approach to assessing the intrinsic targeting properties of NP in a systemic manner, being mainly performed with liposomes, is the creation of formulation libraries in which several structural changes of NP are tested comparatively, such as changes in the type of phospholipids being used.…”

Section: Npc Populations Of the Liver Contribute To Its Tolerogenimentioning

confidence: 65%

“…As an immediate consequence, targeting a specific macrophage population within the liver can be a difficult task. In general, NP internalization by hepatic macrophages was shown to be driven by different mechanisms including macropinocytosis, clathrin- as well as caveolin-mediated endocytosis, and additional endocytotic pathways [ 85 ]. There are two major cell type-targeting strategies: passive and active targeting.…”

Section: Npc Populations Of the Liver Contribute To Its Tolerogenimentioning

confidence: 99%

Role of Liver-Mediated Tolerance in Nanoparticle-Based Tumor Therapy

Cacicedo

Medina‐Montano

Kaps

et al. 2020

Cells

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In the last decades, the use of nanocarriers for immunotherapeutic purposes has gained a lot of attention, especially in the field of tumor therapy. However, most types of nanocarriers accumulate strongly in the liver after systemic application. Due to the default tolerance-promoting role of liver non-parenchymal cells (NPCs), Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), their potential role on the immunological outcome of systemic nano-vaccination approaches for therapy of tumors in the liver and in other organs needs to be considered. Concerning immunological functions, KCs have been the focus until now, but recent studies have elucidated an important role of LSECs and HSCs as well. Therefore, this review aims to summarize current knowledge on the employment of nanocarriers for immunotherapeutic therapy of liver diseases and the overall role of liver NPCs in the context of nano-vaccination approaches. With regard to the latter, we discuss strategies on how to address liver NPCs, aiming to exploit and modulate their immunological properties, and alternatively how to avoid unwanted engagement of nano-vaccines by liver NPCs for tumor therapy.

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“…Passive targeting is usually responsible for macrophage uptake of unmodified nanoparticles of medium size (10~300 nm diameter), which include most extracellular vehicles (EVs) and liposomes. These nanoparticles primarily accumulate at infection or inflammation sites as a result of phagocytosis and/or macropinocytosis by monocyte/macrophage-lineage cells that are abundantly present at these sites 47 , although in vitro studies indicate that some nanoparticles are also preferentially engulfed via clathrin- or caveolin-mediated endocytosis mechanisms 48 . Both natural and synthetic nanoparticles can be modified to promote their active targeting to macrophages via different approaches that add macrophage-specific molecules to their surfaces 12 .…”

Section: Therapeutic Approaches To Modulate Macrophage Dysfunctionmentioning

confidence: 99%

“…Synthetic nanocarriers ( e.g. , solid-lipid, polymeric, or metallic nanoparticles) using this strategy have been developed for macrophage-targeted drug delivery in models of inflammatory and infectious diseases 12 , 48 . Several studies have employed different modification strategies to target nanoparticle drug delivery systems to macrophages.…”

Section: Therapeutic Approaches To Modulate Macrophage Dysfunctionmentioning

confidence: 99%

Nanomedicine therapies modulating Macrophage Dysfunction: a potential strategy to attenuate Cytokine Storms in severe infections

et al. 2020

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Cytokine storms, defined by the dysregulated and excessive production of multiple pro-inflammatory cytokines, are closely associated with the pathology and mortality of several infectious diseases, including coronavirus disease 2019 (COVID-19). Effective therapies are urgently needed to block the development of cytokine storms to improve patient outcomes, but approaches that target individual cytokines may have limited effect due to the number of cytokines involved in this process. Dysfunctional macrophages appear to play an essential role in cytokine storm development, and therapeutic interventions that target these cells may be a more feasible approach than targeting specific cytokines. Nanomedicine-based therapeutics that target macrophages have recently been shown to reduce cytokine production in animal models of diseases that are associated with excessive proinflammatory responses. In this mini-review, we summarize important studies and discuss how macrophage-targeted nanomedicines can be employed to attenuate cytokine storms and their associated pathological effects to improve outcomes in patients with severe infections or other conditions associated with excessive pro-inflammatory responses. We also discuss engineering approaches that can improve nanocarriers targeting efficiency to macrophages, and key issues should be considered before initiating such studies.

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Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

Cited by 104 publications

References 144 publications

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Role of Liver-Mediated Tolerance in Nanoparticle-Based Tumor Therapy

Nanomedicine therapies modulating Macrophage Dysfunction: a potential strategy to attenuate Cytokine Storms in severe infections

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