Self-assembled PEGylated albumin nanoparticles (SPAN) as a platform for cancer chemotherapy and imaging.

ABSTRACT: Paclitaxel (PTX) is used as a major antitumor agent for the treatment of recurrent and metastatic breast cancer. For the clinical application of PTX, it needs to be dissolved in an oil/detergent-based solvent due to its poor solubility in an aqueous medium. However, the formulation often causes undesirable complications including hypersensitivity reactions and limited tumor distribution, resulting in a lower dose-dependent antitumor effect. Herein, we introduce a facile and oil-free method to prepare albumin-based PTX nanoparticles for efficient systemic cancer therapy using a conjugate of human serum albumin (HSA) and poly(ethyleneglycol) (PEG). PTX were efficiently incorporated in the self-assembled HSA-PEG nanoparticles (HSA-PEG/PTX) using a simple film casting and re-hydration procedure without additional processes such as application of high pressure/shear or chemical crosslinking. The spherical HSA-PEG nanoparticle with a hydrodynamic diameter of ca. 280?nm mediates efficient cellular delivery, leading to comparable or even higher cytotoxicity in various breast cancer cells than that of the commercially available Abraxane^®. When systemically administered in a mouse xenograft model for human breast cancer, the HSA-PEG-based nanoparticle formulation exhibited an extended systemic circulation for more than 96?h and enhanced intratumoral accumulation, resulting in a remarkable anticancer effect and prolonged survival of the animals.

SUBMITTER: Lee JE 

PROVIDER: S-EPMC6060380 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature