title: Biotin/Folate-decorated Human Serum Albumin Nanoparticles of Docetaxel: Comparison of Chemically Conjugated Nanostructures and Physically Loaded Nanoparticles for Targeting of Breast Cancer.
abstract: Docetaxel (DTX) is a widely used chemotherapeutic agent with very low water solubility. Conjugation of DTX to human serum albumin (HSA) is an effective way to increase its water solubility. Attachment of folic acid (FA) or biotin as targeting moieties to DTX-HSA conjugates may lead to active targeting and specific uptake by cancer cells with overexpressed FA or biotin receptors. In this study, FA or biotin molecules were attached to DTX-HSA conjugates by two different methods. In one method, FA or biotin molecules were attached to remaining NH2 residues of HSA in DTX-HSA conjugate by covalent bonds. In the second method, HSA-FA or HSA-biotin conjugates were synthesized separately and then combined by DTX-HSA conjugate in proper ratio to prepare nanoparticles containing DTX-HSA plus HSA-FA or HSA-biotin. Cell viability of different nanoparticle was evaluated on MDA-MB-231 (folate receptor positive), A549 (folate receptor negative), and 4T1 (biotin receptor positive) and showed superior cytotoxicity compared with free docetaxel (Taxotere). In vivo studies of DTX-HSA-FA and DTX-HSA-biotin conjugates in BULB/c mice, tumorized by 4T1 cell line, showed the conjugates prepared in this study were more powerful in the reduction in tumor size and increasing the survival rate when compared to free docetaxel.
authors.affiliation: Nanomedicine and Biomaterial Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Nateghian
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Goodarzi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14174, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Nanomedicine and Biomaterial Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Dr. Shariati Hospital, North Karegar Ave., Tehran University of Medical Sciences, Tehran, 1411413137, Iran.|Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khorramizadeh
authors.affiliation: Nanomedicine and Biomaterial Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001710:Biotin / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles; D012709:Serum Albumin / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012709:Serum Albumin; D043823:Taxoids; D000077143:Docetaxel; D001710:Biotin; D005492:Folic Acid
keywords: biotin; conjugated nanostructures; docetaxel; folate; human serum albumin; macromolecular drug delivery; targeted nanoparticles