mp8b00861_si_001.pdf (1.16 MB)
Download fileSialic Acid-Functionalized PEG–PLGA Microspheres Loading Mitochondrial-Targeting-Modified Curcumin for Acute Lung Injury Therapy
journal contribution
posted on 2018-11-15, 00:00 authored by Feiyang Jin, Di Liu, Hui Yu, Jing Qi, Yuchan You, Xiaoling Xu, Xuqi Kang, Xiaojuan Wang, Kongjun Lu, Xiaoying Ying, Jian You, Yongzhong Du, Jiansong JiAcute lung injury (ALI) is a serious
illness without resultful
therapeutic methods commonly. Recent studies indicate the importance
of oxidative stress in the occurrence and development of ALI, and
mitochondria targeted antioxidant has become a difficult and hot topic
in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted
microsphere (MS) for ALI therapy are developed, with triphenylphosphonium
cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically
target the mitochondria, increasing the effect of antioxidant. The
results manifest that with the increase of microsphere, lung distribution
of microsphere is also increased in murine mice, and after SA modification,
the microsphere exhibits the ideal lung-targeted characteristic in
ALI model mice, due to SA efficiently targeting to E-selectin expressed
on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS
has better antioxidative capacity, decreases intracellular ROS generation,
and increases mitochondrial membrane potential, contributing to a
lower apoptosis rate in human umbilical vein endothelial cells (HUVECs)
compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has
been alleviated markedly and the oxidative stress is ameliorated efficiently.
Significant histological improvements by SA/Cur-TPP/MS are further
proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a
promising drug formulation for ALI therapy.