am0c00068_si_001.pdf (607.93 kB)
Core/Shell PEGS/HA Hybrid Nanoparticle Via Micelle-Coordinated Mineralization for Tumor-Specific Therapy
journal contribution
posted on 2020-02-25, 20:48 authored by Zihan Wu, Xiaoyu Ma, Yifan Ma, Zhaogang Yang, Yuan Yuan, Changsheng LiuNanomicelles,
by virtue of their prominent biocompatibility, degradability,
and ability to solubilize hydrophobic drugs, have been widely used
as the most effective delivery platform for anticancer drugs. However,
undesirable drug-loading capacity, unfeasible modification, poor in
vivo stability, and intratumoral penetration remain to be addressed.
Herein, we introduce a novel core/shell PEGylated poly(glycerol sebacate)
(PEGS)/hydroxyapatite (HA) hybrid nanomicelle based on a unique triblock
PEGS substrate with functional carboxyls in terminals and free hydroxyls
as pendant groups. The hydrophobic doxorubicin (DOX) can be controllably
encapsulated in the core of nanomicelles via hydrogen bonding, and
ensuing in situ mineralization of HA occurs as a shell layer with
the electrostatic effect between the carboxylate radical (COO–) and calcium ion (Ca2+). Through optimizing
the coordination of PEGS nanomicelles and HA mineralization, 20–30
nm spherical nanoparticles can be formed with considerable drug loading
(0.38 mg DOX/1 mg nanoparticles) and a sensitive pH-responsive release
(about 50% release amount at pH 5.6 while <5% release amount at
pH 7.4 in 24 h). In further in vitro studies, this PEGS/HA hybrid
nanoparticle system exhibits excellent selective tumor inhibitory
efficacy, while in in vivo studies, high efficacy of tumor suppression
and low incidence of toxicity can be evidenced in a DOX-loaded PEGS/HA
group (71.7% decrease in average tumor volume compared to a control
group after 15 day hypodermic treatment). The core/shell PEGS/HA nanoparticle
coordinated with PEGS nanomicelles and in situ HA mineralization represents
high drug-loading capacity, multifunctional possibility, and tumor-selective
and responsive release profiles and could offer a highly promising
platform for tumor therapy in clinical application.