title: Ultrasound-mediated destruction of oxygen and paclitaxel loaded dual-targeting microbubbles for intraperitoneal treatment of ovarian cancer xenografts.
abstract: Folate receptor (FR) is overexpressed in many epithelial cancers and tumor-associated macrophages (TAMs), which enable it to function as an appropriate target for cancer treatment. We have successfully synthesized multifunctional folate-targeted and oxygen/paclitaxel loaded microbubbles (TOPLMBs) for ultrasound (US) mediated delivery for combination therapy in an intraperitoneal ovarian cancer xenograft model. The TOPLMBs target both ovarian cancer cells and TAMs and provide a promising drug delivery strategy for the combination treatment of ovarian cancer and tumor microenvironment. Microscopic imaging and flow cytometric analysis showed that TOPLMBs significantly penetrated into ovarian cancer cells and tumor-associated macrophages (TAMs) within tumor ascites fluid and the tumor nodules. Immunohistochemical analyses of dissected tumor tissue confirmed the increased tumor apoptosis, the reduced expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD), and the reduced expression of CD68 after treatment (P < 0.05). Our experiment results suggest that intraperitoneal injection of dual-targeting TOPLMBs followed by US mediation provide a promising drug delivery strategy for combination treatment of ovarian cancer and tumor microenvironment with the therapeutic outcome superior to that of conventional therapeutic options.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Shenyin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: shfch2005@163.com.
authors.forename: Shufang
authors.initials: S
authors.lastname: Chang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral / Q000379:methods*; D051379:Mice; D045423:Microbubbles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D010100:Oxygen / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use*; D014465:Ultrasonics / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D010100:Oxygen
keywords: Folate; Macrophages; Microbubbles; Ovarian cancer; Ultrasound