Abstract
Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.
Highlights
IntroductionNanoparticles can be designed for drug delivery by modulating surface properties and composition to improve therapeutic effect and targeting specificity
Nanomedicine aims to improve health and life welfare with nanosized materials.Nanoparticles can be designed for drug delivery by modulating surface properties and composition to improve therapeutic effect and targeting specificity
CD206 or mannose receptor (MR) has the ability to recognize mannosylated or fucosylated glycoproteins and engulf them [81]. This 175 kDa endocytic receptor was first identified in rabbit alveolar macrophages and is a type I transmembrane receptor composed by an extracellular region containing a cysteine-rich (CR) domain that acts as second lectin domain, and a fibronectin type II (FNII) domain that is involved in collagen binding, and multiple C-type lectin-like domains (CTLDs) within a single polypeptide backbone where the binding of sugars terminated in D-mannose, L-fucose, or N-acetyl glucosamine occurs [82]
Summary
Nanoparticles can be designed for drug delivery by modulating surface properties and composition to improve therapeutic effect and targeting specificity. Active targeting can be obtained with surface functionalization of the nanoparticles using specific ligands to reach the target of interest [1]. Taking advantage of this receptor-mediated specificity will reduce toxicity and side-effects to healthy tissues. Macrophages are distributed according to their functions, surface-expressed markers, and secreted cytokines in M1/M2-polarized phenotypes. Receptors frequently expressed on the surface of macrophages constitute a potential target for nanomedicine-based approaches. Nanocarriers can reset the macrophage activation state, as it is the case of the conversion of M2 phenotype to M1 in tumor-associated macrophages [6]. Understanding the interaction mechanisms between nanoparticles and macrophages is essential to a successful and effective nanocarrier’s design towards a therapeutic or prevention strategy
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