title: Use of macrophages to deliver therapeutic and imaging contrast agents to tumors.
abstract: Drug targeting to tumors with limited toxicity and enhanced efficacy of drug is one of the important goals for cancer treatment pharmaceutics. Monocytes/macrophages are able to migrate to tumor sites across the blood barriers by acting as Trojan horses carrying drug cargoes. Taking this advantage, we have intended to develop an efficient administration system using a biologically active carrier of mouse peritoneal macrophage bearing liposomal doxorubicin (macrophage-LP-Dox). We expect that this system could improve the cancer therapeutic efficacy through deeper penetration into tumor even hypoxic region behind tumor blood vessel. We first confirmed that macrophages containing iron oxides could migrate and infiltrate into tumors effectively by MR imaging. Next, we showed that doxorubicin (Dox) encapsulated with liposomes (LP-Dox) was successfully loaded into macrophages, in which the biological activity of macrophage and cytotoxicity of Dox against tumor cells were well preserved. Delivery of Dox into tumor tissue by systemic administration of macrophage-LP-Dox was verified in both subcutaneous and metastasis xenograft tumor models. Importantly, the effective inhibition of in vivo tumor growth was proved with this system. Our results provide the feasibility of macrophages-LP-drug as an active biocarrier for the enhancement of therapeutic effects in cancer treatment and open new perspectives for the active delivery of drugs.
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jinhyang
authors.initials: J
authors.lastname: Choi
authors.forename: Hye-Yeong
authors.initials: HY
authors.lastname: Kim
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Ju
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.forename: Jaesook
authors.initials: J
authors.lastname: Park
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Chung
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Lee
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002465:Cell Movement; D003287:Contrast Media / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D017737:Macrophages, Peritoneal; D008279:Magnetic Resonance Imaging; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis*
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004317:Doxorubicin