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

Abstract

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.

• Authors: Yaya Cheng , Xiangyu Jiao , Zhantong Wang , Orit Jacobson , Maria A Aronova , Yuanyuan Ma , Liangcan He , Yijing Liu , Wei Tang , Liming Deng , Jianhua Zou , Zhen Yang , Mingru Zhang , Yongqiang Wen , Wenpei Fan , Xiaoyuan Chen
• Journal: Biomaterials science (Biomater Sci) Vol. 9 Issue 7 Pg. 2584-2597 (Apr 07 2021) ISSN: 2047-4849 [Electronic] England
• PMID: 33595023 (Publication Type: Journal Article)

Chemical References

• Gold
• Silicon Dioxide
• Hydrogen Peroxide

Topics

• Gold
• Hydrogen Peroxide
• Metal Nanoparticles
• Nanoparticles
• Particle Size
• Silicon Dioxide