title: Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosis-inducing ligand and transferrin for targeting multiple tumor types.
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.
authors: College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.
authors: Sungho
authors: S
authors: Bae
authors: Kyungwan
authors: K
authors: Ma
authors: Tae Hyung
authors: TH
authors: Kim
authors: Eun Seong
authors: ES
authors: Lee
authors: Kyung Taek
authors: KT
authors: Oh
authors: Eun-Seok
authors: ES
authors: Park
authors: Kang Choon
authors: KC
authors: Lee
authors: Yu Seok
authors: YS
authors: Youn
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D012709:Serum Albumin / Q000378:metabolism*; D013499:Surface Properties / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014168:Transferrin / Q000494:pharmacology*
chemical_list: D000588:Amines; D012709:Serum Albumin; D053221:TNF-Related Apoptosis-Inducing Ligand; D014168:Transferrin; D004317:Doxorubicin