title: Irradiation Enhances the Ability of Monocytes as Nanoparticle Carrier for Cancer Therapy.
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.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Pei-Shin
authors.initials: PS
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Yen
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Christopher William
authors.initials: CW
authors.lastname: Woo
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Lo
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Yu-Kuan
authors.initials: YK
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Chi-Shiun
authors.initials: CS
authors.lastname: Chiang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage*; D005434:Flow Cytometry; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy
chemical_list: D000903:Antibiotics, Antineoplastic; D017077:Culture Media, Conditioned; D004317:Doxorubicin