title: Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma.
abstract: Drug delivery using thermosensitive liposomes (TSL) has significant potential for tumor drug targeting and can be combined with local hyperthermia to trigger drug release. Although TSL-mediated drug delivery can be effective by itself, we developed doxorubicin (DOX)-containing CO2 bubble-generating TSL (TSL-C) that were found to enhance the antitumor effects of DOX owing to the synergism between burst release of drug and hyperthermia-induced CO2 generation. An ultrasound imaging system was used to monitor hyperthermia-induced CO2 generation in TSL-C and the results revealed that hyperthermia-induced CO2 generation in TSL-C led to increased DOX release compared to that observed for non-CO2-generating TSL. Moreover, TSL-C significantly inhibited the tumor growth in MDA-MB-231 tumor-bearing mice compared to TSL (p<0.004). Taken together, we demonstrated that the TSL-C platform increased the therapeutic efficacy of cancer chemotherapy and showed the applicability of this approach to increase drug release within the tumor microenvironment. As a novel and highly effective drug delivery platform, TSL-C has great potential for use in a broad range of applications for the treatment of various human diseases.
  
  
  CONCLUSIONS
  We have developed a novel method for drug release from liposomes by gas (CO2) generation in tumor microenvironment. In addition, we demonstrate therapeutic efficacy in breast carcinoma. CO2-generated liposomal doxorubicin is a novel and highly attractive delivery system for anticancer drug with the potential for broad applications in human disease.
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, 268 Chungwondaero, Chungju-Si, Chungcheongbuk-Do 380-701, South Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Ye Won
authors.initials: YW
authors.lastname: Jeon
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, South Korea; Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Yuseong, Daejeon 305-350, South Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, 268 Chungwondaero, Chungju-Si, Chungcheongbuk-Do 380-701, South Korea.
authors.forename: Hat Nim
authors.initials: HN
authors.lastname: Jeon
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, 268 Chungwondaero, Chungju-Si, Chungcheongbuk-Do 380-701, South Korea.
authors.forename: Yeongseon
authors.initials: Y
authors.lastname: Byeon
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Chong Ock
authors.initials: CO
authors.lastname: Lee
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Sun Hang
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, South Korea; Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Yuseong, Daejeon 305-350, South Korea. Electronic address: bcshin@krict.re.kr.
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002245:Carbon Dioxide / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D002245:Carbon Dioxide; D004317:Doxorubicin
keywords: Breast cancer; Cancer; Doxorubicin; Gas generation; Liposome