Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy

Publication date: Available online 22 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jianxiang Huang, Bihan Wu, Zhuxian Zhou, Shiqi Hu, Hongxia Xu, Ying Piao, Hao Zheng, Jianbin Tang, Xiangrui Liu, Youqing ShenAbstractAlbumin is a serum transport protein, which has been utilized as a carrier for a variety of drugs to improve their delivery efficiency and to obtain favorable pharmacokinetic profiles. However, natural albumin possesses only a few high-affinity binding sites for a limited number of drugs. This results in deficiencies in drug-loading and serum stability, and consequently, in impaired therapeutic efficacy. Herein, BSA was modified with different isothiocyanate conjugates (BSA-ITCs), which self-assembled with paclitaxel (PTX) to produce BSA-ITCs/PTX nanoparticles. Among these BSA-ITCs, phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) conjugates effectively loaded PTX and formed highly stable BSA-PEITC35/PTX nanoparticles. Molecular modeling studies suggested that PEITC groups in BSA-PEITC35 can significantly lower the PTX binding free energy. BSA-PEITC35/PTX showed enhanced stability, prolonged blood circulation and increased tumor accumulation than unmodified BSA/PTX, and exerted more potent antitumor activity than both BSA/PTX and Abraxane in subcutaneous mouse tumor models after intravenous administration.Graphical AbstractHere, we designed phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) which self-assembled ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research