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Irradiation Enhances the Ability of Monocytes as Nanoparticle Carrier for Cancer Therapy.

Jiang PS, Yu CF, Yen CY, Woo CW, Lo SH, Huang YK, Hong JH, Chiang CS - PLoS ONE (2015)

Bottom Line: We also showed that BMDMs can take up various imaging and therapeutic agents, although the mobility of BMDMs decreased with increasing load.When BMDMs were differentiated in IR-treated tumor-conditioned medium (IR-CM) in vitro, the nanoparticle load-mediated inhibition of migration was attenuated.The prolonged retention of monocytes within irradiated tumor tissues and the ability of IR-CM to enhance the migratory ability of cargo-laden BMDMs suggest that monocytes pre-conditioned by IR-CM can potentially act as cellular carriers for targeted therapy following conventional RT.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.

ABSTRACT
The tumor-homing ability of monocytes renders them a potential cellular delivery system for alternative cancer therapies, although their migratory ability can be impaired following reagent uptake. Approaches that enhance monocyte tumor homing and promote their migration will improve the clinical value of these cells as cellular carriers. Previous studies have shown that irradiation (IR) can promote macrophage aggregation in hypoxic regions. To investigate whether IR enhances the infiltration of bone marrow-derived monocytes (BMDMs) into tumors, the infiltration of BMDMs from GFP-transgenic mice in a murine prostate adenocarcinoma TRAMP-C1 model was examined by fluorescence microscopy. IR did not increase the number of BMDMs that infiltrated initially, but did increase monocyte retention within IR-treated tumors for up to 2 weeks. We also showed that BMDMs can take up various imaging and therapeutic agents, although the mobility of BMDMs decreased with increasing load. When BMDMs were differentiated in IR-treated tumor-conditioned medium (IR-CM) in vitro, the nanoparticle load-mediated inhibition of migration was attenuated. These IR-CM-differentiated BMDMs delivered polymer vesicles encapsulating doxorubicin to radiation therapy (RT)-induced hypoxic tumor regions, and enhanced the efficacy of RT. The prolonged retention of monocytes within irradiated tumor tissues and the ability of IR-CM to enhance the migratory ability of cargo-laden BMDMs suggest that monocytes pre-conditioned by IR-CM can potentially act as cellular carriers for targeted therapy following conventional RT.

No MeSH data available.


Related in: MedlinePlus

The change of the phenotypes of GFP+ cells within tumors.(A) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen as assayed by flow cytometry for the monocytes differentiated from the bone marrow cells harvested from C57BL/6-Tg(CAG-EGFP)1Osb/J mice in vitro. Bar: SE of 3 independent experiments. (B) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen examined by immunohistochemistry (IHC) within the tumors taken from one day or one week after 25 Gy of irradiation (IR) or shame irradiated (Control). The average percentage of each surface marker of GFP+ cells of 5 randomly selected fields of each tumor from 3 tumor tissues was counted under 40X objective len. Bar: SE of 3 tumor samples. ***: P <0.005 by one way ANOVA test.
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pone.0139043.g002: The change of the phenotypes of GFP+ cells within tumors.(A) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen as assayed by flow cytometry for the monocytes differentiated from the bone marrow cells harvested from C57BL/6-Tg(CAG-EGFP)1Osb/J mice in vitro. Bar: SE of 3 independent experiments. (B) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen examined by immunohistochemistry (IHC) within the tumors taken from one day or one week after 25 Gy of irradiation (IR) or shame irradiated (Control). The average percentage of each surface marker of GFP+ cells of 5 randomly selected fields of each tumor from 3 tumor tissues was counted under 40X objective len. Bar: SE of 3 tumor samples. ***: P <0.005 by one way ANOVA test.

Mentions: To further characterize the phenotype of the infiltrating GFP-BMDMs, flow cytometry (Fig 2) and immunohistochemistry (IHC) (S2 Fig) were used to assess the phenotypic changes of GFP-BMDMs in vitro and in vivo, respectively. After 8 days of differentiation in vitro, all GFP-BMDMs expressed CD45 and CD11b, while 85.4% ± 1.9% expressed F4/80 and 61.0% ± 1.7% expressed CD68+ (Fig 2A). Quantification of staining in tumor tissues showed that 97% of GFP+ cells in control tumors also expressed CD45, 85% expressed CD11b, 62% expressed F4/80, and approximately 47% were CD68+ (Fig 2B). These ratios did not change over time, although these proportions were slightly lower in comparison to the in vitro results. IR treatment (25 Gy) did not significantly alter the ratio of CD45+ GFP+ and CD11b+ GFP+ cells, although there was a significant increase in the number of CD68+ GFP+ and F4/80+ GFP+ cells 1 week after IR (Fig 2B).


Irradiation Enhances the Ability of Monocytes as Nanoparticle Carrier for Cancer Therapy.

Jiang PS, Yu CF, Yen CY, Woo CW, Lo SH, Huang YK, Hong JH, Chiang CS - PLoS ONE (2015)

The change of the phenotypes of GFP+ cells within tumors.(A) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen as assayed by flow cytometry for the monocytes differentiated from the bone marrow cells harvested from C57BL/6-Tg(CAG-EGFP)1Osb/J mice in vitro. Bar: SE of 3 independent experiments. (B) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen examined by immunohistochemistry (IHC) within the tumors taken from one day or one week after 25 Gy of irradiation (IR) or shame irradiated (Control). The average percentage of each surface marker of GFP+ cells of 5 randomly selected fields of each tumor from 3 tumor tissues was counted under 40X objective len. Bar: SE of 3 tumor samples. ***: P <0.005 by one way ANOVA test.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4587928&req=5

pone.0139043.g002: The change of the phenotypes of GFP+ cells within tumors.(A) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen as assayed by flow cytometry for the monocytes differentiated from the bone marrow cells harvested from C57BL/6-Tg(CAG-EGFP)1Osb/J mice in vitro. Bar: SE of 3 independent experiments. (B) The percentage of GFP+ cells co-express CD45, CD11b, F4/80, or CD68 antigen examined by immunohistochemistry (IHC) within the tumors taken from one day or one week after 25 Gy of irradiation (IR) or shame irradiated (Control). The average percentage of each surface marker of GFP+ cells of 5 randomly selected fields of each tumor from 3 tumor tissues was counted under 40X objective len. Bar: SE of 3 tumor samples. ***: P <0.005 by one way ANOVA test.
Mentions: To further characterize the phenotype of the infiltrating GFP-BMDMs, flow cytometry (Fig 2) and immunohistochemistry (IHC) (S2 Fig) were used to assess the phenotypic changes of GFP-BMDMs in vitro and in vivo, respectively. After 8 days of differentiation in vitro, all GFP-BMDMs expressed CD45 and CD11b, while 85.4% ± 1.9% expressed F4/80 and 61.0% ± 1.7% expressed CD68+ (Fig 2A). Quantification of staining in tumor tissues showed that 97% of GFP+ cells in control tumors also expressed CD45, 85% expressed CD11b, 62% expressed F4/80, and approximately 47% were CD68+ (Fig 2B). These ratios did not change over time, although these proportions were slightly lower in comparison to the in vitro results. IR treatment (25 Gy) did not significantly alter the ratio of CD45+ GFP+ and CD11b+ GFP+ cells, although there was a significant increase in the number of CD68+ GFP+ and F4/80+ GFP+ cells 1 week after IR (Fig 2B).

Bottom Line: We also showed that BMDMs can take up various imaging and therapeutic agents, although the mobility of BMDMs decreased with increasing load.When BMDMs were differentiated in IR-treated tumor-conditioned medium (IR-CM) in vitro, the nanoparticle load-mediated inhibition of migration was attenuated.The prolonged retention of monocytes within irradiated tumor tissues and the ability of IR-CM to enhance the migratory ability of cargo-laden BMDMs suggest that monocytes pre-conditioned by IR-CM can potentially act as cellular carriers for targeted therapy following conventional RT.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.

ABSTRACT
The tumor-homing ability of monocytes renders them a potential cellular delivery system for alternative cancer therapies, although their migratory ability can be impaired following reagent uptake. Approaches that enhance monocyte tumor homing and promote their migration will improve the clinical value of these cells as cellular carriers. Previous studies have shown that irradiation (IR) can promote macrophage aggregation in hypoxic regions. To investigate whether IR enhances the infiltration of bone marrow-derived monocytes (BMDMs) into tumors, the infiltration of BMDMs from GFP-transgenic mice in a murine prostate adenocarcinoma TRAMP-C1 model was examined by fluorescence microscopy. IR did not increase the number of BMDMs that infiltrated initially, but did increase monocyte retention within IR-treated tumors for up to 2 weeks. We also showed that BMDMs can take up various imaging and therapeutic agents, although the mobility of BMDMs decreased with increasing load. When BMDMs were differentiated in IR-treated tumor-conditioned medium (IR-CM) in vitro, the nanoparticle load-mediated inhibition of migration was attenuated. These IR-CM-differentiated BMDMs delivered polymer vesicles encapsulating doxorubicin to radiation therapy (RT)-induced hypoxic tumor regions, and enhanced the efficacy of RT. The prolonged retention of monocytes within irradiated tumor tissues and the ability of IR-CM to enhance the migratory ability of cargo-laden BMDMs suggest that monocytes pre-conditioned by IR-CM can potentially act as cellular carriers for targeted therapy following conventional RT.

No MeSH data available.


Related in: MedlinePlus