A photothermal-triggered nitric oxide nanogenerator combined with siRNA for precise therapy of osteoarthritis by suppressing macrophage inftammation

被引:78
作者
Chen, Xu [1 ]
Liu, Yanan [1 ]
Wen, Yayu [1 ]
Yu, Qianqian [1 ]
Liu, Jiawei [1 ]
Zhao, Yingyu [1 ]
Liu, Jie [1 ]
Ye, Gang [1 ,2 ]
机构
[1] Jinan Univ, Dept Chem, Guangzhou, Guangdong, Peoples R China
[2] Jinan Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou 510632, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
NANOPARTICLES; GENERATION; DELIVERY; IDENTIFICATION; MITOCHONDRIA; NANOCARRIERS; NANODOTS; SYSTEMS; COMPLEX;
D O I
10.1039/c8nr10013f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Although nitric oxide (NO) can be used to treat osteoarthritis (OA) by inhibiting inflammation, a method for the accurately controlled release of NO in inflammatory cells is still elusive. Herein, photothermal-trig-gered NO nanogenerators NO-Hb@siRNMaPLGA-PEG (NHsPP) were constructed by assembling photo-thermal-agents and NO molecules within nanoparticles. In the NHsPP nanoparticles the hemoglobin (Hb) nanoparticles can act as a NO carrier which can absorb near-infrared light at 650 nm (0.5 W cm(-2)) and convert it into heat to trigger the release of NO. Moreover, after loading Notchl-siRNA, precise treatment can be achieved. Furthermore, using the synergistic effect of photothermal therapy, the NHsPP nano-particles achieved simultaneous treatment with NO, siRNA and PTT. Through this combination therapy, the therapeutic effect of the NHsPP nanoparticles was significantly enhanced compared to the treatment groups using only NO, siRNA or PTT. This combination therapy inhibits the inflammatory response effectively by reducing the level of pro-inflammatory cytokines and the macrophage response. Subsequently, guided by dual-modal imaging, the NHsPP nanoparticles can not only accumulate effectively in OA mice, but can also reduce the inflammatory response and efficiently prevent cartilage erosion, without causing toxic side effects in the major organs. Therefore, this novel photothermal nanoparticle-based NO-releasing system is expected to be a potential alternative for clinical inflammatory disease therapy and may provide image guidance when combined with other nanotherapy systems.
引用
收藏
页码:6693 / 6709
页数:17
相关论文
共 52 条
[1]   NOTCH TARGETS AND THEIR REGULATION [J].
Bray, Sarah ;
Bernard, Fred .
NOTCH SIGNALING, 2010, 92 :253-275
[2]   Nitric Oxide Releasing Materials Triggered by Near-Infrared Excitation Through Tissue Filters [J].
Burks, Peter T. ;
Garcia, John V. ;
GonzalezIrias, Ricardo ;
Tillman, Jason T. ;
Niu, Mutong ;
Mikhailovsky, Alexander A. ;
Zhang, Jinping ;
Zhang, Fan ;
Ford, Peter C. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (48) :18145-18152
[3]  
Chang Y.-T., 2014, ADV MATER, V24, P3309
[4]   Pompon-like RuNPs-Based Theranostic Nanocarrier System with Stable Photoacoustic Imaging Characteristic for Accurate Tumor Detection and Efficient Phototherapy Guidance [J].
Chen, Gengjia ;
Xu, Meng ;
Zhao, Shuang ;
Sun, Jing ;
Yu, Qianqian ;
Liu, Jie .
ACS APPLIED MATERIALS & INTERFACES, 2017, 9 (39) :33645-33659
[5]   Intelligent Albumin-MnO2 Nanoparticles as pH-/H2O2-Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy [J].
Chen, Qian ;
Feng, Liangzhu ;
Liu, Jingjing ;
Zhu, Wenwen ;
Dong, Ziliang ;
Wu, Yifan ;
Liu, Zhuang .
ADVANCED MATERIALS, 2016, 28 (33) :7129-+
[6]   Overcoming the Heat Endurance of Tumor Cells by Interfering with the Anaerobic Glycolysis Metabolism for Improved Photothermal Therapy [J].
Chen, Wei-Hai ;
Luo, Guo-Feng ;
Lei, Qi ;
Hong, Sheng ;
Qiu, Wen-Xiu ;
Liu, Li-Han ;
Cheng, Si-Xue ;
Zhang, Xian-Zheng .
ACS NANO, 2017, 11 (02) :1419-1431
[7]   Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine [J].
Cheng, Ji-Xin ;
Xie, X. Sunney .
SCIENCE, 2015, 350 (6264)
[8]   Emerging roles of the γ-secretase-notch axis in inflammation [J].
Cheng, Yi-Lin ;
Choi, Yuri ;
Sobey, Christopher G. ;
Arumugam, Thiruma V. ;
Jo, Dong-Gyu .
PHARMACOLOGY & THERAPEUTICS, 2015, 147 :80-90
[9]   Light-Induced Acid Generation on a Gatekeeper for Smart Nitric Oxide Delivery [J].
Choi, Hyung Woo ;
Kim, Jihoon ;
Kim, Jinhwan ;
Kim, Yonghwi ;
Song, Hyun Beom ;
Kim, Jeong Hun ;
Kim, Kimoon ;
Kim, Won Jong .
ACS NANO, 2016, 10 (04) :4199-4208
[10]   Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review [J].
Chow, Clara K. ;
Thakkar, Jay ;
Bennett, Alex ;
Hillis, Graham ;
Burke, Michael ;
Usherwood, Tim ;
Vo, Kha ;
Rogers, Kris ;
Atkins, Emily ;
Webster, Ruth ;
Chou, Michael ;
Dehbi, Hakim-Moulay ;
Salam, Abdul ;
Patel, Anushka ;
Neal, Bruce ;
Peiris, David ;
Krum, Henry ;
Chalmers, John ;
Nelson, Mark ;
Reid, Christopher M. ;
Woodward, Mark ;
Hilmer, Sarah ;
Thom, Simon ;
Rodgers, Anthony .
LANCET, 2017, 389 (10073) :1035-1042