Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo

Abstract

Effect of alkoxyamines on normal and tumor cells was studied in vitro and in vivo. In vitro experiments showed that alkoxyamines produce a dose-dependent toxic effect on cells of human breast tumor MCF7 line. Transplantation of Krebs-2 ascites carcinoma cells preincubated with alkoxyamines to mice did not induce tumor growth. An opposite effect was observed in normal mouse cells: functional activity of peritoneal macrophages increased. The possibility of using alkoxyamines as theranostic agents is discussed.

Design of a Targeting and Oxygen-Independent Platform to Improve Photodynamic Therapy: A Proof of Concept

“…Thus, the release radical as a therapeutic agent triggered the apoptosis of cancer cells in vitro and the nitroxide was used as a diagnostic probe in imaging by Overhauser magnetic resonance imaging. Recently, we optimized the efficiency of these reactive species to destroy malignant cells in vitro and reported in vivo experiments using mouse …”

“…Recently, we optimized the efficiency of these reactive species to destroy malignant cells in vitro 8 and reported in vivo experiments using mouse. 9 Another limit of PDT is the low selectivity of the majority of the commercial PSs. The selectivity is, therefore, because of the possibility to confine the PS by restricting the light illumination to a specific region.…”

Alkylverdazyls as a Source of Alkyl Radicals for Light-Triggered Cancer Cell Death

“…Despite the vast amount of results concerning the efficacy of PDT agents, serious issues have been raised in the case of oxygen-deficient tumors, where the PDT dramatically loses efficiency. , To overcome such drawbacks, methods of oxygen-independent treatment have been proposed recently . In such a case, the reactive radical species can be generated directly from organic compounds with labile bonds spontaneously , or under external stimuli. − Despite active evaluation of alkoxyamines as novel therapeutic and theranostic agents, their application is still challengeable for light-assisted generation of active radical species due to the weak absorbance of visible light. ,− Indeed, the direct implementation of UV irradiation makes obvious difficulties in clinical practice and can be dangerous for patients. Moreover, light-triggered homolysis of alkoxyamines is well documented in polymer and material sciences, whereas the first two reports on the usage of light-sensitive alkoxyamines as anticancer agents have been reported recently. , …”

An enzymatic acetal/hemiacetal conversion for the physiological temperature activation of the alkoxyamine C–ON bond homolysis

“…[24][25][26] For a few years, 27 our groups have promoted the therapeutic application of alkoxyamines as drugs against cancer. [28][29][30] For such an application, we aim to combine four antagonistic features: a highly stable precursor (or pro-drug), a highly reactive drug, random reactivity, and specific addressing. The aim is to circumvent drugresistant cancer by using highly reactive and unselective drugs, and to improve the patient welfare by using highly selective pro-drugs via specific addressing, which is a step towards personalized medicine.…”