α-Amylase- and Redox-Responsive Nanoparticles for Tumor-Targeted Drug Delivery

• DOI: 10.1021/acsami.7b04066
• Publication Date: 2017-05-17T12:10:10Z
• Authors: Yihui Li; Hang Hu; Qing Zhou; Yanxiao Ao; Chen Xiao; Jiangling Wan; Ying Wan; Huibi Xu; Zifu Li; Xiangliang Yang
• Keywords: Reducing agent

Paclitaxel (PTX) is an effective antineoplastic agent and shows potent antitumor activity against a wide spectrum of cancers. Yet, the clinical use PTX limited by its poor aqueous solubility side effects associated with current therapeutic formulation. To tackle these obstacles, we report, for first time, α-amylase- redox-responsive nanoparticles based on hydroxyethyl starch (HES) tumor-targeted delivery PTX. conjugated onto HES redox-sensitive disulfide bond to form HES–SS-PTX, which was confirmed results from NMR, high-performance liquid chromatography-mass spectrometry, Fourier transform infrared spectrometry. The HES–SS-PTX conjugates assemble into stable monodispersed (NPs), as characterized Dynamic light scattering, transmission electron microscopy, atomic force microscopy. In blood, α-amylase will degrade shell thus decrease size NPs, facilitating NP extravasation penetration tumor. A pharmacokinetic study demonstrated that NPs have longer half-life than commercial formulation (Taxol). As consequence, accumulate more in tumor compared extent Taxol, shown vivo imaging study. Under reductive conditions, could disassemble quickly evidenced their triggered collapse, burst drug release, enhanced cytotoxicity 4T1 cells presence reducing agent. Collectively, show improved efficacy (63.6 vs 52.4%) reduced toxicity tumor-bearing mice those Taxol. These highlight advantages HES-based showing great translation potential cancer chemotherapy.