Antioxidant Nanomedicine Significantly Enhances the Survival Benefit of Radiation Cancer Therapy by Mitigating Oxidative Stress‐Induced Side Effects

Abstract

Oxidative stress‐induced off‐target effects limit the therapeutic window of radiation therapy. Although many antioxidants have been evaluated as radioprotective agents, none of them are in widespread clinical use, owing to the side effects of the antioxidants themselves and the lack of apparent benefit. Aiming for a truly effective radioprotective agent in radiation cancer therapy, the performance of a self‐assembling antioxidant nanoparticle (herein denoted as redox nanoparticle; RNP) is evaluated in the local irradiation of a subcutaneous tumor‐bearing mouse model. Since RNP is covered with a biocompatible shell layer and possesses a core–shell type structure of several tens of nanometers in size, its lifetime in the systemic circulation is prolonged. Moreover, since 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO), one of the most potent antioxidants, is covalently encapsulated in the core of RNP, it exerts intense antioxidant activity and induces fewer adverse effects by avoiding leakage of the TEMPO molecules. Preadministration of RNP to the mouse model effectively mitigates side effects in normal tissues and significantly extends the survival benefit of radiation cancer therapy. Moreover, RNP pretreatment noticeably increases the apoptosis/necrosis ratio of radiation‐induced cell death, a highly desirable property to reduce the chronic side effects of ionizing irradiation.

Enhancement of Proton Therapy Efficiency by Noble Metal Nanoparticles Is Driven by the Number and Chemical Activity of Surface Atoms

“…Metal nanoparticles (NPs) in the tumor volume can serve as sensitizers for enhancing radiotherapy (RT) efficiency. [ 1–10 ] The basis for combining RT with NPs was formed by the pioneering work of Hainfeld and Slatkin in 2004, in which the authors irradiated thiol‐glucose ligand coated gold nanoparticles (Au NPs) with X‐rays. The Au NPs having sizes of 1–3 nm were intravenously injected into EMT‐6 (breast cancer tumor cells), and an 86% increase in the long‐term survival of the animals was proven.…”

“…Metal nanoparticles (NPs) in the tumor volume can serve as sensitizers for enhancing radiotherapy (RT) efficiency. [1][2][3][4][5][6][7][8][9][10] The in the tumor cell viability compared to untreated cells. [17] In a follow-up study, they also performed similar experiments with Au (diameter of 2-13 nm) and Fe (diameter of ≈14 nm) NPs, noting a 90% and 75% reduction in tumor volume, respectively while irradiation in the absence of NPs resulted in only an 18% reduction.…”

Pt–Fe3O4, Pd–Fe3O4, and Au–Fe3O4 Nanoheterodimers and Their Efficacy as Radiosensitizers in Cancer Therapy

“…In contrast, intracellular Au–Fe 3 O 4 or Pt–Fe 3 O 4 NHDs fostered the MCF-10A MCS growth, which is mainly due to the antioxidant caffeic acid ligands acting as ROS scavengers. Since caffeic acid is poorly soluble in water and therefore not suitable for medical application, the fusion of the antioxidant caffeic acid with redox-active Au-Fe 3 O 4 and Pt–Fe 3 O 4 NHDs is tailored for nanoantioxidant therapy as being bioavailable and as acting as a radioprotective antioxidant in healthy cells. , The antioxidant effect of caffeic acid depends on the intracellular ROS concentration. Cancer cells, for example, differ from healthy cells by their higher H 2 O 2 concentration.…”

“…To provide the Au–Fe 3 O 4 NHDs with a radioprotective function for healthy cells, the NHDs were functionalized with the natural ROS scavenger and anticancer drug caffeic acid . The combination of antioxidants and nanomaterials, also known as nano-oxidants, increases the bioavailability and biocompatibility of the radioprotective antioxidants. , Caffeic acid-functionalized Au–Fe 3 O 4 NHDs were shown to act as radioprotectors for nontumorigenic breast epithelial cells (MCF-10A) and as X-ray dose enhancers in breast cancer cells (MCF-7) in (2D) monolayer cell cultures . In recent studies, we showed that this effect was also preserved in (3D) multicellular spheroids. , …”

Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

“…Adapted with permission. [545][546][547][548][549][550][551][552][553][554] Copyright, Wiley, American Chemical Society, and Elsevier.…”