Apoptotic Cells Can Deliver Chemotherapeutics to Engulfing Macrophages and Suppress Inflammatory Cytokine Production

Perez, Beatriz H.; Paquette, Nicholas; Païdassi, Helena; Zhai, Bo; White, Kristin; Skvirsky, Rachel C.; Lacy‐Hulbert, Adam; Stuart, Lynda M.

doi:10.1074/jbc.m112.340489

Cited by 9 publications

(6 citation statements)

References 20 publications

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“…[9][10][11] Following apoptotic cell engulfment, macrophages, and neutrophils can reduce the production of pro-inflammatory cytokines such as tumor necrosis factor-α. 12,13 In addition, macrophages can differentiate into a range of anti-inflammatory and pro-healing phenotypes that contribute to wound resolution. [14][15][16] There are also "non-professional" phagocytes, cell types that are not derived from bone marrow but are capable of phagocytosis even though it is not one of their primary functions.…”

Section: Introductionmentioning

confidence: 99%

Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution

et al. 2021

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“…[ 7 ] The detailed role of Eto in cancer treatment and immune system modulation may seem elusive but studies have suggested that cancerous cells killed through Eto treatment induce macrophages to produce TNF α and other pro‐inflammatory signals unlike some other chemotherapeutic agents. [ 68,69 ] Although, Eto is not considered to be a classic “immunogenic cell death” inducer as it does not induce translocation of calreticulin, it can however cause the release of inflammatory mediators ATP and HMGB1. [ 70 ] Conversely, macrophages have been shown to either enhance or reduce Eto‐induced apoptosis depending on the phenotype (i.e., M1 or M2 macrophages).…”

Section: Discussionmentioning

confidence: 99%

Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model

Abdel-Bar

Walters

Wang

et al. 2021

Adv Healthcare Materials

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This study investigated the feasibility of lipid polymer hybrid nanoparticles (LPH) as a platform for the combinatorial delivery of small interfering RNA (siRNA) and etoposide (Eto). Different Eto loaded LPH formulations (LPH Eto) are prepared. The optimized cationic LPH Eto with a particle size of 109.66 ± 5.17 nm and Eto entrapment efficiency (EE %) of 80.33 ± 2.55 is used to incorporate siRNA targeting CD47 (siCD47), a do not eat me marker on the surface of cancer cells. The siRNA‐encapsulating LPH (LPH siNEG‐Eto) has a particle size of 115.9 ± 4.11 nm and siRNA EE % of 63.54 ± 4.36 %. LPHs improved the cellular uptake of siRNA in a dose‐ and concentration‐dependent manner. Enhanced cytotoxicity (3.8‐fold higher than Eto solution) and high siRNA transfection efficiency (≈50 %) are obtained. An in vivo biodistribution study showed a preferential uptake of the nanosystem into lung, liver, and spleen. In an experimental pseudo‐metastatic B16F10 lung tumor model, a superior therapeutic outcome can be observed in mice treated with combinatory therapy. Immunological studies revealed elevated CD4+, CD8+ cells, and macrophages in the lung following combinatory treatment. The study suggests the potential of the current system for combinatory chemotherapy and immunotherapy for the treatment of lung cancer or lung metastasis.

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“…The administration of stabilized apoptotic cells can also be used for delivering substances of interest such as therapeutic proteins (for protein replacement therapy) or drugs to recipient macrophages. 34 …”

Section: Discussionmentioning

confidence: 99%

Stabilization of apoptotic cells: generation of zombie cells

et al. 2014

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Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn2+ (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.

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Apoptotic Cells Can Deliver Chemotherapeutics to Engulfing Macrophages and Suppress Inflammatory Cytokine Production

Abstract: Background: Cytotoxic agents are used to induce cell death to study apoptotic cell-induced immune regulation.

Cited by 9 publications

References 20 publications

Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution

Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution

Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model

Stabilization of apoptotic cells: generation of zombie cells

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