title: Antiangiogenic-targeting drug-loaded microbubbles combined with focused ultrasound for glioma treatment.
abstract: Current chemotherapeutic agents do not only kill tumor cells but also induce systemic toxicity that significantly limits their dosage. Focused ultrasound (FUS) in the presence of microbubbles (MBs) is capable of transient and local opening of the blood-brain barrier (BBB) that enhances chemotherapeutic drug delivery into the brain parenchyma for glioma treatment. Our previous results demonstrated the success of combining the use of drug (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-loaded MBs with FUS-induced BBB opening to improve local drug delivery and reduce systemic toxicity. Here we introduce novel VEGF-targeting, drug-loaded MBs that significantly further enhance targeted drug release and reduce tumor progression in a rat model, using the FUS-BBB opening strategy. This study suggests a promising direction for future MB design aimed at targeted brain tumor therapy, and the possible future extension of MB application towards theragnostic use.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Fan
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Ting
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Hsieh
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media; D016503:Drug Delivery Systems; D004996:Ethidium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000628:therapy*; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D018675:Toxicity Tests; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D014465:Ultrasonics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D042461:Vascular Endothelial Growth Factor A; D004996:Ethidium; D002330:Carmustine