10.1021/acsami.7b04066.s001
Yihui Li
Yihui
Li
Hang Hu
Hang
Hu
Qing Zhou
Qing
Zhou
Yanxiao Ao
Yanxiao
Ao
Chen Xiao
Chen
Xiao
Jiangling Wan
Jiangling
Wan
Ying Wan
Ying
Wan
Huibi Xu
Huibi
Xu
Zifu Li
Zifu
Li
Xiangliang Yang
Xiangliang
Yang
α‑Amylase-
and Redox-Responsive Nanoparticles for Tumor-Targeted Drug Delivery
American Chemical Society
2017
4 T 1 tumor-bearing mice
4 T 1 tumor cells
α- amylase
HES-based α- amylase
redox-sensitive disulfide bond
PTX
vivo imaging study
NP
transmission electron microscopy
NMR
Tumor-Targeted Drug Delivery Paclitaxel
burst drug release
2017-05-17 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/_Amylase-_and_Redox-Responsive_Nanoparticles_for_Tumor-Targeted_Drug_Delivery/5049022
Paclitaxel (PTX)
is an effective antineoplastic agent and shows potent antitumor activity
against a wide spectrum of cancers. Yet, the wide clinical use of
PTX is limited by its poor aqueous solubility and the side effects
associated with its current therapeutic formulation. To tackle these
obstacles, we report, for the first time, α-amylase- and redox-responsive
nanoparticles based on hydroxyethyl starch (HES) for the tumor-targeted
delivery of PTX. PTX is conjugated onto HES by a redox-sensitive disulfide
bond to form HES–SS-PTX, which was confirmed by results from
NMR, high-performance liquid chromatography-mass spectrometry, and
Fourier transform infrared spectrometry. The HES–SS-PTX conjugates
assemble into stable and monodispersed nanoparticles (NPs), as characterized
with Dynamic light scattering, transmission electron microscopy, and
atomic force microscopy. In blood, α-amylase will degrade the
HES shell and thus decrease the size of the HES–SS-PTX NPs,
facilitating NP extravasation and penetration into the tumor. A pharmacokinetic
study demonstrated that the HES–SS-PTX NPs have a longer half-life
than that of the commercial PTX formulation (Taxol). As a consequence,
HES–SS-PTX NPs accumulate more in the tumor compared with the
extent of Taxol, as shown in an in vivo imaging study. Under reductive
conditions, the HES–SS-PTX NPs could disassemble quickly as
evidenced by their triggered collapse, burst drug release, and enhanced
cytotoxicity against 4T1 tumor cells in the presence of a reducing
agent. Collectively, the HES–SS-PTX NPs show improved in vivo
antitumor efficacy (63.6 vs 52.4%) and reduced toxicity in 4T1 tumor-bearing
mice compared with those of Taxol. These results highlight the advantages
of HES-based α-amylase- and redox-responsive NPs, showing their
great clinical translation potential for cancer chemotherapy.