Transport by circulating myeloid cells drives liposomal accumulation in inflamed synovium

Deprez, Joke; Verbeke, R; Meulewaeter, Sofie; Aernout, Ilke; Dewitte, Heleen; Decruy, Tine; Coudenys, Julie; Duyse, Julie Van; Isterdael, Gert Van; Peer, Dan; Meel, Roy van der; Smedt, Stefaan C. De; Jacques, Peggy; Elewaut, Dirk; Lentacker, Ine

doi:10.1038/s41565-023-01444-w

“…Historic studies demonstrated myeloid cells can modulate the pharmacokinetics, biodistribution, and efficacy of nanotherapeutics 12, 13 . Recent studies argued that circulating myeloid cells, such as inflammation-associated monocytes and granulocytes can actively transport nanoparticles from the blood to the tissue when they infiltrate the inflamed tissue 14, 43, 47 . Our study confirmed this alternative mechanism in a mouse model of glioma, by showing that highly tumor-infiltrative M-MDSCs can contribute to the tumor accumulation of OH dendrimers.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to their immunosuppressive features, M-MDSCs, as phagocytes 10, 11 , could also significantly affect the in vivo fate of nanoparticles. Historic studies have established the critical roles of myeloid cells in clearing nanoparticles 12, 13 , while emerging evidence has shown that myeloid cells in circulation can take up nanoparticles and actively transport them to the inflamed tissue 4, 14, 15 . M-MDSCs are significantly elevated in the peripheral blood of high-grade glioblastoma patients, accounting for as much as 10% of total cells in the peripheral blood and 30% of total peripheral blood mononuclear cells 16, 17 .…”

Section: Introductionmentioning

confidence: 99%

Systemically targeting monocytic MDSCs using dendrimers and their cell-level biodistribution kinetics

Littrell,

Takacs,

Sankara

et al. 2024

Preprint

0

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The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

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“…After a single dose of 200 μL EBen-Lip (composed of 150 μM EBen and 5 mM lipids) in PBS, weak fluorescence was observed at the subcutaneous tumor, likely due to the enhanced permeability and retention (EPR) effect of nano- sized liposomes (Figure 5h). [34] However, when functionalized with active targeting groups, EBen-Lip-cRGD-treated mice showed significantly enhanced NIR-II emission patterns at the tumor site (Figure 5h and 5i). After a 24-hour observation period, the mice were sacrificed for ex vivo tumor imaging.…”

Section: Methodsmentioning

confidence: 98%

NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking

Meng,

Gao,

Zhou

et al. 2024

Angewandte Chemie

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Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near‐infrared window (NIR‐II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation‐caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a “passive” method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE‐containing liposomes were functionalized with cyclic arginine‐glycine‐aspartic acid (cRGD) peptides, serving as tumor‐targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR‐II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new‐generation of membrane‐targeting probes to facilitate the liposome‐based medicine research.

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“…Chemie sized liposomes (Figure 5h). [34] However, when functionalized with active targeting groups, EBen-Lip-cRGD-treated mice showed significantly enhanced NIR-II emission patterns at the tumor site (Figure 5h and 5i). After a 24-hour observation period, the mice were sacrificed for ex vivo tumor imaging.…”

Section: Methodsmentioning

confidence: 98%

NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking

Meng,

Gao,

Zhou

et al. 2024

Angew Chem Int Ed

0

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Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near‐infrared window (NIR‐II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation‐caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a “passive” method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE‐containing liposomes were functionalized with cyclic arginine‐glycine‐aspartic acid (cRGD) peptides, serving as tumor‐targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR‐II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new‐generation of membrane‐targeting probes to facilitate the liposome‐based medicine research.

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Transport by circulating myeloid cells drives liposomal accumulation in inflamed synovium

Cited by 16 publications

References 71 publications

Systemically targeting monocytic MDSCs using dendrimers and their cell-level biodistribution kinetics

Systemically targeting monocytic MDSCs using dendrimers and their cell-level biodistribution kinetics

NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking

NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking

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