TY - JOUR
T1 - Macrophages as Drug Delivery Carriers for Acoustic Phase-Change Droplets
AU - Fan, Ching Hsiang
AU - Lee, Ya Hsuan
AU - Ho, Yi Ju
AU - Wang, Chung Hsin
AU - Kang, Shih Tsung
AU - Yeh, Chih Kuang
N1 - Funding Information:
The authors gratefully acknowledge the support of the Ministry of Science and Technology, Taiwan, under Grant Nos. 106-2627-M-007-007, 106-2221-E-007-008 and 106-2119-M-182-001; the National Tsing Hua University (Hsinchu, Taiwan) under Grant No. 106 N522 CE1; and Chang Gung Memorial Hospital (Linkou, Taiwan) under Grant No. CIRPD2 E0051.
Funding Information:
The authors gratefully acknowledge the support of the Ministry of Science and Technology, Taiwan , under Grant Nos. 106-2627-M-007-007 , 106-2221-E-007-008 and 106-2119-M-182-001 ; the National Tsing Hua University (Hsinchu, Taiwan) under Grant No. 106 N522 CE1 ; and Chang Gung Memorial Hospital (Linkou, Taiwan) under Grant No. CIRPD2 E0051 .
Publisher Copyright:
© 2018 World Federation for Ultrasound in Medicine and Biology
PY - 2018/7
Y1 - 2018/7
N2 - The major challenges in treating malignant tumors are transport of therapeutic agents to hypoxic regions and real-time assessment of successful drug release via medical imaging modalities. In this study, we propose the use of macrophages (RAW 264.7 cells) as carriers of drug-loaded phase-change droplets to penetrate ischemic or hypoxic regions within tumors. The droplets consist of perfluoropentane, lipid and the chemotherapeutic drug doxorubicin (DOX, DOX-droplets). The efficiency of DOX-droplet uptake, migration mobility and viability of DOX-droplet-loaded macrophages (DLMs) were measured using a transmembrane cell migration assay, the alamarBlue assay and flow cytometric analysis, respectively. Our results indicate the feasibility of utilizing macrophages as DOX-droplet carriers (DOX payload of DOX-droplets: 459.3 ± 35.8 µg/mL, efficiency of cell uptake DOX-droplets: 88.8 ± 3.5%). The migration mobility (total number of migrated microphages) of DLMs decreased to 32.3% compared with that of healthy macrophages, but the DLMs provided contrast-enhanced ultrasound imaging (1.7-fold enhancement) and anti-tumor effect (70.9% cell viability) after acoustic droplet vaporization, suggesting the potential theranostic applications of DLMs. Future work will assess the tumor penetration ability of DLMs, mechanical effect of droplet vaporization on in vivo anti-tumor therapy and the release of the carried drug by ultrasound-triggered vaporization.
AB - The major challenges in treating malignant tumors are transport of therapeutic agents to hypoxic regions and real-time assessment of successful drug release via medical imaging modalities. In this study, we propose the use of macrophages (RAW 264.7 cells) as carriers of drug-loaded phase-change droplets to penetrate ischemic or hypoxic regions within tumors. The droplets consist of perfluoropentane, lipid and the chemotherapeutic drug doxorubicin (DOX, DOX-droplets). The efficiency of DOX-droplet uptake, migration mobility and viability of DOX-droplet-loaded macrophages (DLMs) were measured using a transmembrane cell migration assay, the alamarBlue assay and flow cytometric analysis, respectively. Our results indicate the feasibility of utilizing macrophages as DOX-droplet carriers (DOX payload of DOX-droplets: 459.3 ± 35.8 µg/mL, efficiency of cell uptake DOX-droplets: 88.8 ± 3.5%). The migration mobility (total number of migrated microphages) of DLMs decreased to 32.3% compared with that of healthy macrophages, but the DLMs provided contrast-enhanced ultrasound imaging (1.7-fold enhancement) and anti-tumor effect (70.9% cell viability) after acoustic droplet vaporization, suggesting the potential theranostic applications of DLMs. Future work will assess the tumor penetration ability of DLMs, mechanical effect of droplet vaporization on in vivo anti-tumor therapy and the release of the carried drug by ultrasound-triggered vaporization.
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U2 - 10.1016/j.ultrasmedbio.2018.03.009
DO - 10.1016/j.ultrasmedbio.2018.03.009
M3 - Article
C2 - 29685589
AN - SCOPUS:85045896784
SN - 0301-5629
VL - 44
SP - 1468
EP - 1481
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 7
ER -