title: Paclitaxel-liposome-microbubble complexes as ultrasound-triggered therapeutic drug delivery carriers.
abstract: Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered drug delivery to treat malignant tumors. However, the efficacy for ultrasound-assisted chemotherapy in vivo and the underlying mechanisms remain to be elucidated. Here, we investigated the feasibility of using paclitaxel-liposome-microbubble complexes (PLMC) as possible ultrasound (US)-triggered targeted chemotherapy against breast cancer. PTX-liposomes (PL) were conjugated to the microbubble (MB) surface through biotin-avidin linkage, increasing the drug-loading efficiency of MBs. The significant increased release of payloads from liposome-microbubble complexes was achieved upon US exposure. We used fluorescent quantum dots (QDs) as a model drug to show that released QDs were taken up by 4T1 breast cancer cells treated with QD-liposome-microbubble complexes (QLMC) and US, and uptake depended on the exposure time and intensity of insonication. We found that PLMC plus US inhibited tumor growth more effectively than PL plus US or PLMC without US, not only in vitro, but also in vivo. Histologically, the inhibition of tumor growth appeared to result from increased apoptosis and reduced angiogenesis in tumor xenografts. In addition, a significant increase of drug concentration in tumors was observed in comparison to treatment with non-conjugated PL or PLMC without US. The significant increase in an antitumor efficacy of PLMC plus US suggests their potential use as a new targeted US chemotherapeutic approach to inhibit breast cancer growth.
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Zhiting
authors.initials: Z
authors.lastname: Deng
authors.forename: Qiaofeng
authors.initials: Q
authors.lastname: Jin
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
authors.forename: Junru
authors.initials: J
authors.lastname: Wu
authors.forename: Robin
authors.initials: R
authors.lastname: Shandas
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005240:Feasibility Studies; D005260:Female; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015612:Phonophoresis / Q000379:methods*; D045663:Quantum Dots; D012995:Solubility; D013010:Sonication; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D017239:Paclitaxel