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Biomaterials. 2012 Feb;33(5):1536-46. doi: 10.1016/j.biomaterials.2011.10.050. Epub 2011 Nov 25.

Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosis-inducing ligand and transferrin for targeting multiple tumor types.

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  • 1College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.

Abstract

Human serum albumin (HSA) nanoparticles (NPs) surface modified with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and transferrin, and containing doxorubicin were designed and prepared. Surface amines of HSA were reversibly protected with dimethylmaleic anhydride (DMMA), and HSA-NPs were prepared using a desolvation technique. Furthermore, the surfaces of HSA-NPs were modified with thiolated TRAIL or transferrin using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The prepared TRAIL/transferrin plus doxorubicin HSA-NPs were characterized by TEM, FE-SEM, and particle size analysis, and their cytotoxic and apoptotic activities were evaluated in several cancer cell lines, namely, HCT 116, doxorubicin-resistant MCF-7, and CAPAN-1. In addition, the tumor-targeting abilities of NPs were assessed using an infrared imaging system in HCT 116-xenografted nu/nu mice. Results showed that the TRAIL/transferrin/doxorubicin HSA-NPs had remarkable cytotoxic and apoptotic activities in all cancer cells examined with a general or a drug-resistant character, and that these NPs had obvious synergistic cytotoxic effects particularly on CAPAN-1 cells. Moreover, these HSA-NPs were effectively localized to tumors in a HCT 116-xenografted nu/nu mouse over 32 h. The findings of this study suggest that the described TRAIL/transferrin/doxorubicin HSA-NPs are a useful targeting agent capable of killing different types of tumor cells in various tissue organs.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
22118776
[PubMed - indexed for MEDLINE]
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