Use of macrophages to deliver therapeutic and imaging contrast agents to tumors

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• 作者：Jinhyang Choi^a ; Hye-Yeong Kim^a ; Eun Jin Ju^a ; Joohee Jung^a ; Jaesook Park^a ; Hye-Kyung Chung^b ; Jin Seong Lee^c ; Jung Shin Lee^a ; ^d ; Heon Joo Park^e ; Si Yeol Song^a ; ^f ; Seong-Yun Jeong^a ; ^{syj@amc.seoul.kr} ; Eun Kyung Choi^a ; ^b ; ^f ; ^{ekchoi@amc.seoul.kr}
• 关键词：Macrophage ; Liposomal doxorubicin ; Drug delivery ; Tumor target
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：June, 2012
• 卷：33
• 期：16
• 页码：4195-4203
• 文件大小：1568 K

摘要

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聽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.