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Lipid bubbles (LB) are compounds that increase the vascular permeability of the tumor under diagnostic ultrasound (US) exposure and enable the effective transport of drugs to tumor cells. The aim of our study was to establish a novel drug delivery technique for chemotherapy and to identify the most effective anticancer drugs for the bubble US\u2010mediated drug delivery system (BUS\u2010DDS) in gynecological cancer treatments. We constructed xenograft models using cervical cancer (HeLa) and uterine endometrial cancer (HEC1B) cell lines. Lipid bubbles were injected i.v., combined with either cisplatin (CDDP), pegylated liposomal doxorubicin (PLD), or bevacizumab, and US was applied to the tumor. We compared the enhanced chemotherapeutic effects of these drugs and determined the optimal drugs for BUS\u2010DDS. Tumor volume reduction of HeLa and HEC1B xenografts following cisplatin treatment was significantly enhanced by BUS\u2010DDS. Both CDDP and PLD significantly enhanced the antitumor effects of BUS\u2010DDS in HeLa tumors; however, volume reduction by BUS\u2010DDS was insignificant when combined with bevacizumab, a humanized anti\u2010vascular endothelial growth factor mAb. The BUS\u2010DDS did not cause any severe adverse events and significantly enhanced the antitumor effects of cytotoxic drugs. The effects of bevacizumab, which were not as dose\u2010dependent as those of the two drugs used prior, were minimal. Our data suggest that BUS\u2010DDS technology might help achieve \u201creinforced targeting\u201d in the treatment of gynecological cancers.<\/jats:p>","DOI":"10.1111\/cas.14907","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T15:47:36Z","timestamp":1617292056000},"page":"2493-2503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Enhanced antitumor activity of combined lipid bubble ultrasound and anticancer drugs in gynecological cervical cancers"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-3411","authenticated-orcid":false,"given":"Kohei","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Faculty of Medicine The University of Tokyo Tokyo 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