Mannosylated Polyrotaxanes for Increasing Cellular Uptake Efficiency in Macrophages through Receptor-Mediated Endocytosis

Shibaguchi, Kai; Tamura, Atsushi; Terauchi, Masahiko; Matsumura, Mitsuaki; Miura, Hiroyuki; Yui, Nobuhiko

doi:10.3390/molecules24030439

Cited by 21 publications

(20 citation statements)

References 45 publications

(73 reference statements)

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“…Furthermore, the uptake of M-EV in RAW264.7 cells was 2.20-, 5.78-fold higher than that of M-EV in DC2.4 and A549 cells, respectively. These results indicated the specificity of M-EV to macrophages, which were consistent with many other studies showing high expression level of mannose receptors on macrophages [55][56][57]. The uptake of various nanoformulations was also evaluated in murine RAW264.7 cells.…”

Section: "Eat Me/don't Eat Me" Strategy In Macrophages In Vitrosupporting

confidence: 89%

“…It is well established that the MR is mostly expressed on the surface of most types of macrophages and dendritic cells (DCs), although they are also found in certain endothelial cells, smooth muscle cells, retinal epithelial cells, and so on [ 55 ]. There are plenty of studies validating the high expression of the mannose receptor (CD206) on macrophages [ 56 , 57 ]. So, several studies have developed the mannose-modified nanoparticles to target macrophages overexpressing mannose receptors [ 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

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A combined “eat me/don't eat me” strategy based on extracellular vesicles for anticancer nanomedicine

Belhadj

Deng

et al. 2020

J of Extracellular Vesicle

141

109

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A long-term and huge challenge in nanomedicine is the substantial uptake and rapid clearance mediated by the mononuclear phagocyte system (MPS), which enormously hinders the development of nanodrugs. Inspired by the natural merits of extracellular vesicles, we therefore developed a combined "eat me/don't eat me" strategy in an effort to achieve MPS escape and efficient drug delivery. Methodologically, cationized mannan-modified extracellular vesicles derived from DC2.4 cells were administered to saturate the MPS (eat me strategy). Then, nanocarriers fused to CD47-enriched exosomes originated from human serum were administered to evade phagocytosis by MPS (don't eat me strategy). The nanocarriers were also loaded with antitumor drugs and functionalized with a novel homing peptide to promote the tumour tissue accumulation and cancer cell uptake (eat me strategy). The concept was proven in vitro as evidenced by the reduced endocytosis of macrophages and enhanced uptake by tumour cells, whereas prolonged circulation time and increased tumour accumulation were demonstrated in vivo. Specially, the strategy induced a 123.53% increase in tumour distribution compared to conventional nanocarrier. The study both shed light on the challenge overcoming of phagocytic evasion and provided a strategy for significantly improving therapeutic outcomes, potentially permitting active drug delivery via targeted nanomedicines.

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Section: "Eat Me/don't Eat Me" Strategy In Macrophages In Vitrosupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

A combined “eat me/don't eat me” strategy based on extracellular vesicles for anticancer nanomedicine

Belhadj

Deng

et al. 2020

J of Extracellular Vesicle

141

109

View full text Add to dashboard Cite

show abstract

“…Both the CD ring and the polymer chain can be functionalized for the improved efficiency or cellular internalization. Recently α-CD ring was modified with α-D-mannose for the improved mannose receptor mediated endocytosis [17]. Folate-terminated polyrotaxanes were developed by modifying PEG chains and target mitochondrium [18].…”

Section: Cyclodextrin Associates Polypseudorotaxanes and Polyrotaxanesmentioning

confidence: 99%

“…The endocytosis of functionalized cyclodextrins should be distinguished from the above-mentioned non-specific processes. In this cases, folate-appended methyl-β-cyclodextrin [133] or mannose-modified α-cyclodextrin based polyrotaxanes [17] can be mentioned as examples for receptor-mediated endocytosis through the interaction with folate and mannose receptors respectively.…”

Section: Endocytosis Of Cyclodextrinsmentioning

confidence: 99%

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Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

et al. 2019

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Cyclodextrins are widely used excipients, composed of glucopyranose units with a cyclic structure. One of their most important properties, is that their inner cavity is hydrophobic, while their surface is hydrophilic. This enables them for the complex formation with lipophilic molecules. They have several applications in the pharmaceutical field like solubility enhancers or the building blocks of larger drug delivery systems. On the other hand, they have numerous effects on cells or biological barriers. In this review the most important properties of cyclodextrins and cyclodextrin-based drug delivery systems are summarized with special focus on their biological activity.

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MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF‐κB Translocation in T24 Bladder Cancer Cells

Hohagen,

Sánchez,

Herbst

et al. 2024

Adv Healthcare Materials

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D‐mannose is widely used as non‐antibiotic treatment for bacterial urinary tract infections. This application is based on a well‐studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D‐mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll‐like receptor 4 (TLR4) and caveolin‐1 (CAV‐1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF‐κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin‐1, and NF‐κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.

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Mannosylated Polyrotaxanes for Increasing Cellular Uptake Efficiency in Macrophages through Receptor-Mediated Endocytosis

Cited by 21 publications

References 45 publications

A combined “eat me/don't eat me” strategy based on extracellular vesicles for anticancer nanomedicine

A combined “eat me/don't eat me” strategy based on extracellular vesicles for anticancer nanomedicine

Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF‐κB Translocation in T24 Bladder Cancer Cells

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