Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy

Jianxiang Huang; Bihan Wu; Zhuxian Zhou; Shiqi Hu; Hongxia Xu; Ying Piao; Hao Zheng; Jianbin Tang; Xiangrui Liu; Youqing Shen

doi:10.1016/j.nano.2019.102058

Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy

Nanomedicine. 2019 Oct:21:102058. doi: 10.1016/j.nano.2019.102058. Epub 2019 Jul 22.

Authors

Affiliations

¹ Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
² Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China. Electronic address: zhouzx@zju.edu.cn.
³ Institute of Marine Chemistry and Environment, Ocean College, Zhejiang University, Zhoushan, China. Electronic address: zhenghao@zju.edu.cn.

PMID: 31344500
DOI: 10.1016/j.nano.2019.102058

Abstract

Albumin 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.

Keywords: Albumin; Binding free energies; Drug binding ligand; Drug delivery; Paclitaxel; Phenethyl isothiocyanate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albumin-Bound Paclitaxel* / chemistry
Albumin-Bound Paclitaxel* / pharmacology
Animals
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Drug Carriers* / chemistry
Drug Carriers* / pharmacology
Humans
Isothiocyanates / chemistry
Isothiocyanates / pharmacology
Mice
Models, Molecular*
Nanoparticles* / chemistry
Nanoparticles* / therapeutic use
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Serum Albumin, Bovine / chemistry
Serum Albumin, Bovine / pharmacology

Substances

Albumin-Bound Paclitaxel
Antineoplastic Agents
Drug Carriers
Isothiocyanates
Serum Albumin, Bovine
phenethyl isothiocyanate