Biphasic synthesis of biodegradable urchin-like mesoporous organosilica nanoparticles for enhanced cellular internalization and precision cascaded therapy

被引：7

作者：

Cheng, Yaya ^{[1
,2
]}

Jiao, Xiangyu ^{[1
]}

Wang, Zhantong ^{[2
]}

Jacobson, Orit ^{[2
]}

Aronova, Maria A. ^{[3
]}

Ma, Yuanyuan ^{[2
]}

He, Liangcan ^{[2
]}

Liu, Yijing ^{[2
]}

Tang, Wei ^{[2
]}

Deng, Liming ^{[2
]}

Zou, Jianhua ^{[2
]}

Yang, Zhen ^{[2
]}

Zhang, Mingru ^{[2
]}

Wen, Yongqiang ^{[1
]}

Fan, Wenpei ^{[4
]}

Chen, Xiaoyuan ^{[2
,5
,6
]}

机构：

[1] Univ Sci & Technol Beijing, Daxing Res Inst, Dept Chem & Biol Engn, Beijing Key Lab Bioengn & Sensing Technol, Beijing 100083, Peoples R China

[2] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA

[3] Natl Inst Biomed Imaging & Bioengn NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA

[4] China Pharmaceut Univ, Ctr Adv Pharmaceut & Biomat, State Key Lab Nat Med, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Peoples R China

[5] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 119228, Singapore

[6] Natl Univ Singapore, Fac Engn, Singapore 119228, Singapore

来源：

BIOMATERIALS SCIENCE | 2021年 / 9卷 / 07期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

Gold nanoparticles - Silica nanoparticles - Synthesis (chemical) - Glucose sensors - Tumors - Particle size - Amino acids - Covalent bonds - Sulfur compounds - Glucose - Nitric oxide - Catalyst activity - Medical applications;

D O I：

10.1039/d1bm00015b

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

It is widely accepted that a small particle size and rough surface can enhance tumor tissue accumulation and tumor cellular uptake of nanoparticles, respectively. Herein, sub-50 nm urchin-inspired disulfide bond-bridged mesoporous organosilica nanoparticles (UMONs) featured with a spiky surface and glutathione (GSH)-responsive biodegradability were successfully synthesized by a facile one-pot biphasic synthesis strategy for enhanced cellular internalization and tumor accumulation. l-Arginine (LA) is encapsulated into the mesopores of UMONs, whose outer surface is capped with the gatekeeper of ultrasmall gold nanoparticles, i.e., UMONs-LA-Au. On the one hand, the mild acidity-activated uncapping of ultrasmall gold can realize a tumor microenvironment (TME)-responsive release of LA. On the other hand, the unique natural glucose oxidase (GOx)-mimicking catalytic activity of ultrasmall gold can catalyze the decomposition of intratumoral glucose to produce acidic hydrogen peroxide (H2O2) and gluconic acid. Remarkably, these products can not only further facilitate the release of LA, but also catalyze the LA-H2O2 reaction for an increased nitric oxide (NO) yield, which realizes synergistic catalysis-enhanced NO gas therapy for tumor eradication. The judiciously fabricated UMONs-LA-Au present a paradigm of TME-responsive nanoplatforms for both enhanced cellular uptake and tumor-specific precision cascaded therapy, which broadens the range of practical biomedical applications and holds a significant promise for the clinical translation of silica-based nanotheranostics.

引用

页码：2584 / 2597

页数：14

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