X‐Ray‐Controlled Generation of Peroxynitrite Based on Nanosized LiLuF₄:Ce³⁺ Scintillators and their Applications for Radiosensitization

Abstract

Peroxynitrite (ONOO ), the reaction product derived from nitric oxide (NO) and superoxide (O ), is a potent oxidizing and nitrating agent that modulates complex biological processes and promotes cell death. Therefore, it can be expected that the overproduction of ONOO in tumors can be an efficient approach in cancer therapy. Herein, a multifunctional X-ray-controlled ONOO generation platform based on scintillating nanoparticles (SCNPs) and UV-responsive NO donors Roussin's black salt is reported, and consequently the mechanism of their application in enhanced therapeutic efficacy of radiotherapy is illustrated. Attributed to the radioluminescence and high X-ray-absorbing property of SCNPs, the nanocomposite can produce NO and O simultaneously when excited by X-ray irradiation. Such simultaneous release of NO and O ensures the efficient X-ray-controlled generation of ONOO in tumors. Meanwhile, the application of X-rays as the excitation source can achieve better penetration depth and induce radiotherapy in this nanotherapeutic platform. It is found that the X-ray-controlled ONOO -generation platform can efficiently improve the radiotherapy efficiency via directly damaging DNA, downregulating the expression of the DNA-repair enzyme, and overcoming the hypoxia-associated resistance in radiotherapy. Therefore, this SCNP-based platform may provide a new combinatorial strategy of ONOO and radiotherapy to improve cancer treatment.

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

“…Besides direct excitation, X‐ray can also indirectly activate the gas donors to release gasotransmitters for synchronous/synergistic RT/gas therapy by taking advantage of the X‐ray‐to‐light conversion of scintillators. Very recently, Du et al designed a multifunctional X‐ray‐responsive NO release nanoplatform (RBS‐T‐SCNPs) through the construction of SCNP (LiLuF 4 :Ce) and a UV‐sensitive NO donor (Roussin's black salt, RBS) ( Figure a) . The tocopheryl polyethylene glycol 1000 succinate (TPGS) was attached onto the surface of LiLuF 4 :Ce nanoparticles (T‐SCNPs) for improved biocompatibility.…”

“…h) Relative A549 tumor volume curves of different groups of mice after varied treatments. a–h) Reproduced with permission . Copyright 2018, Wiley‐VCH.…”

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Besides, due to the advantages of facile manipulation, high tissue penetrating depth and energy focusing, other exogenous stimuli, like X‐ray, ultrasound and microwave, have also been widely integrated with functionalized nanomaterials for remote‐controlled gas release and biomedical therapeutic application . For example, our group previously reported a multifunctional X‐ray controlled ONOO − generation platform containing scintillating nanoparticles (SCNPs) and UV‐responsive NO donors Roussin's black salt (RBS) . Based on the high X‐ray‐absorbing property of SCNPs, the nanocomposite could produce NO and O 2 •− simultaneously when excited by X‐ray irradiation and further generate powerful ONOO − for cancer therapy.…”

X‐ray‐Controlled Bilayer Permeability of Bionic Nanocapsules Stabilized by Nucleobase Pairing Interactions for Pulsatile Drug Delivery

“…In addition, the upconverting nanoparticles typically have low conversion efficiency that also limits UV application. To obviate these limitations, scintillating nanoparticles that emit photons in the visible and UV region upon X‐ray irradiation have been developed . However, phototriggered isomerization of azobenzene is accompanied by microstructural rearrangement and irreversible nanocapsule disruption .…”