Oxygen-Independent Photocleavage of Radical Nanogenerator for Near-IR-Gated and H2 O-Mediated Free-Radical Nanotherapy.

Abstract

The oxygen-dependent nature and limited penetration capacity of visible light render the low efficiency of photodynamic therapy in hypoxic and deep-seated tumors. Therefore, the development of oxygen-free photoactivated chemotherapy (PACT) to generate cytotoxic reactive oxygen species by near-IR (NIR) light-cleavable photocages is in high demand. Here, an oxygen-irrelevant PACT strategy based on NIR light-triggered hydroxyl radicals (•OH) generation is developed for free-radical nanotherapy. Blebbistatin-loaded upconversion of mesoporous silica nanoparticles (UCSNs-B) is established to facilitate the high loading efficiency of blebbistatin and implement the efficient transformation of NIR light into blue light for unprecedented direct photorelease of oxygen-independent •OH. Under NIR laser irradiation, UCSNs-B converted NIR light into blue light, thus enabling the photocleavage of blebbistatin to induce the burst of •OH. The •OH burst under NIR laser irradiation further induces cancer cell apoptosis and significant suppression of hypoxic tumors. In addition, the gadolinium ion (Gd3+ )-doped UCSNs-B are used as contrast agents in magnetic resonance imaging to facilitate real-time monitoring of the therapeutic processes. This study effectively demonstrates that the UCSNs-B act as NIR light-triggered photocages to facilitate oxygen-irrelevant •OH bursts, thus providing insights into the development of efficient PACT nanoagents for cancer treatment.

• Authors: Yixin Chen, Huijing Xiang, Shangwen Zhuang, Yujia Shen, Yu Chen, Jun Zhang
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 33 Issue 36 Pg. e2100129 (Sep 2021) ISSN: 1521-4095 [Electronic] Germany
• PMID: 34302402 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents
• Free Radicals
• Heterocyclic Compounds, 4 or More Rings
• Reactive Oxygen Species
• blebbistatin
• Silicon Dioxide
• Gadolinium
• Oxygen

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Free Radicals (chemistry)
• Gadolinium (chemistry)
• Heterocyclic Compounds, 4 or More Rings (chemistry, metabolism)
• Humans
• Infrared Rays
• Magnetic Resonance Imaging
• Mice
• Nanomedicine
• Nanoparticles (chemistry)
• Neoplasms (diagnostic imaging, therapy)
• Neoplasms, Experimental
• Oxygen (chemistry, pharmacology)
• Photochemotherapy (methods)
• Reactive Oxygen Species (chemistry)
• Silicon Dioxide (chemistry)