Advanced strategies to evade the mononuclear phagocyte system clearance of nanomaterials

Abstract

Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites of action, but their delivery efficacy is severely limited by a series of biological barriers, especially the mononuclear phagocytic system (MPS)-the first and major barrier encountered by systemically administered nanomaterials. Herein, the current strategies for evading the MPS clearance of nanomaterials are summarized. First, engineering nanomaterials methods including surface modification, cell hitchhiking, and physiological environment modulation to reduce the MPS clearance are explored. Second, MPS disabling methods including MPS blockade, suppression of macrophage phagocytosis, and macrophages depletion are examined. Last, challenges and opportunities in this field are further discussed.

Recent Advances of Emerging Spleen‐Targeting Nanovaccines for Immunotherapy

“…[ 45 ] Therefore, the vaccination processes and therapeutic effects of spleen‐targeting nanovaccines in different animal models should be carefully examined before their clinical translation. iii) Biosafety of nanovaccines in clinics : Generally, the NPs tend to be opsonized by the opsonin and albumin in the blood after IV injection, followed by the phagocytosis of MΦs in the liver and spleen. [ 118 ] To enhance the accumulation of nanovaccines in the spleen, high‐dose nanomaterials are usually administered with long‐term exposure in mice. Excessive treatment with nanovaccines may induce systemic chronic inflammation or local endothelial cell destruction to accelerate tumor metastasis, and cause serious destruction to the metabolic organs such as the liver, spleen, lung, and kidney.…”

Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport

“…Besides its potential, engineering of live cells ex vivo also has limitations, such as the risk of mitigating cell transmigration abilities, reduced cell viability and fast degradation of the cargos before reaching their target, high cost and insufficient quantities of harvested cells. 410,411 An emerging strategy is the in vivo hitchhiking of immune cells with NPs which give them an ‘eat me’ signal in order to exploit their migratory abilities to the diseased tissue. For example, Li M. et al cloaked cisplatin loaded NPs with bacteria-secreted outer membrane vesicles so as to be recognized by neutrophils upon intravenous administration and internalized by them.…”

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

“…The greatest barrier contributing to degradation and rapid elimination of nanoparticles from circulatory system is the immune system‐mediated opsonization 3–5 . The mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) are primary pathways leading to nanoparticulate degradation due to presence of elaborate network of circulating macrophages, dendritic cells, and stationary macrophages present in spleen, liver and bone marrow 6,7 . Nanoparticles like liposomes (20–100 nm), polyplexes (50–150 nm), and colloidal particles such microemulsion and polymeric‐micelles, administered in the blood, are translocated into various organs such as liver and are further engulfed by circulatory and stationary macrophages like Kuffer cells 8,9 .…”

“…[3][4][5] The mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) are primary pathways leading to nanoparticulate degradation due to presence of elaborate network of circulating macrophages, dendritic cells, and stationary macrophages present in spleen, liver and bone marrow. 6,7 Nanoparticles like liposomes (20-100 nm), polyplexes (50-150 nm), and colloidal particles such microemulsion and polymeric-micelles, administered in the blood, are translocated into various organs such as liver and are further engulfed by circulatory and stationary macrophages like Kuffer cells. 8,9 This event causes subsequent degradation and elimination of the drug, preventing it to reach therapeutic concentrations in blood and target site.…”