Premium
Biotin/Folate‐decorated Human Serum Albumin Nanoparticles of Docetaxel: Comparison of Chemically Conjugated Nanostructures and Physically Loaded Nanoparticles for Targeting of Breast Cancer
Author(s) -
Nateghian Navid,
Goodarzi Navid,
Amini Mohsen,
Atyabi Fatemeh,
Khorramizadeh Mohammad Reza,
Dinarvand Rassoul
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12624
Subject(s) - folate receptor , human serum albumin , biotin , conjugate , chemistry , docetaxel , cytotoxicity , biochemistry , cancer cell , in vitro , biology , cancer , mathematical analysis , genetics , mathematics
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 NH 2 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.