Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.
Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment.
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Wen-Yu
WY
Pan
Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan, ROC.
Kun-Ju
KJ
Lin
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Chieh-Cheng
CC
Huang
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Wei-Lun
WL
Chiang
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Yu-Jung
YJ
Lin
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Wei-Chih
WC
Lin
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Er-Yuan
EY
Chuang
Department of Cardiovascular Surgery, Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan, ROC; Collage of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. Electronic address: cvsyenchang@gmail.com.
Yen
Y
Chang
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address: hwsung@mx.nthu.edu.tw.
Hsing-Wen
HW
Sung
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D061986:MCF-7 Cells; D060526:Magnetic Fields; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D013482:Superoxide Dismutase; D002117:Calcitriol
Chemopreventive agent; Combination chemotherapy; Reactive oxygen species; Sequential drug release; Synergistic anticancer effect