期刊
BIOMATERIALS
卷 31, 期 30, 页码 7766-7775出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.06.038
关键词
Self-assembled nanoparticle; Targeted nanoplatform; Adhesion molecule; Tumor targeting; Drug delivery; Payload encapsulation
资金
- American Heart Association
- NIH [R01 GM090320]
- Business for International Cooperative R&D between Industry, Academy, and Research Institute (Korea Small and Medium Business Administration [00042115]
Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed targeted polymeric nanoparticles called amphiphilic urethane acrylate nonionomer (UAN) for encapsulation of diverse water-insoluble drugs and diagnostic agents, as well as for simple and reproducible surface conjugation of targeting ligands. Using monoclonal antibodies or lymphocyte function-associated antigen-1 (LFA-1) I domain engineered for varying affinities to intercellular adhesion molecule (ICAM)-1, we were able to deliver UAN nanoparticles to human cancer cells with the efficiency dependent on the strength of the molecular interactions and the degree of ICAM-1 expression on cell surface. Compared to non-specific uptake of free drugs, targeted delivery of UAN nanoparticles carrying equal amount of drugs produced more potent cytotoxicity. Notably, without the targeting ligands attached, UAN nanoparticles were largely precluded from nonspecific uptake by the cells, resulting in much lower toxicity. The versatility of our UAN nanoparticles in both payload encapsulation and presentation of targeting ligands may facilitate developing a robust platform for evaluating various combinations of cancer drugs and molecular interactions toward developing effective cancer therapy formulations. (C) 2010 Elsevier Ltd. All rights reserved.
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