Journal
BIOMATERIALS
Volume 33, Issue 16, Pages 4195-4203Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.02.022
Keywords
Macrophage; Liposomal doxorubicin; Drug delivery; Tumor target
Funding
- Korea Science and Engineering Foundation
- Ministry of Education, Science and Technology of Korea [2008-03876]
- Ministry for Health and Welfare, Republic of Korea [A062254, A102059]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [KRF-2008-313E00444]
- ASAN Institute for Life Science, Seoul, Korea [2009-445]
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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 bio-carrier for the enhancement of therapeutic effects in cancer treatment and open new perspectives for the active delivery of drugs. (c) 2012 Elsevier Ltd. All rights reserved.
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