BACKGROUND: Reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, trigger biodegradation of polymer-based nanoparticles (NPs) bearing pinacol-type boronic ester groups. These NPs may selectively release their cargo, in this case paclitaxel (PTX), at the high levels of ROS present in the intracellular environment of inflamed tissues and most tumors. PURPOSE: The main objective was to determine anti-tumor efficacy of PTX-loaded ROS-sensitive NPs and to examine whether macrophage infiltration had any impact on treatment efficacy. METHODS: NPs were synthesized and their characteristics in the presence of H2O2 were demonstrated. Both confocal microscopy as well as flow cytometry approaches were used to determine degradation of ROS-sensitive NPs. HeLa cells were cultured in vitro and used to establish tumor xenografts in nude mice. In vivo experiments were performed to understand toxicity, biodistribution and anti-tumor efficacy of the NPs. Moreover, we performed immunohistochemistry on tumor sections to study infiltration of M1 and M2 subsets of macrophages. RESULTS: We demonstrated that PTX delivered in NPs containing a ROS-sensitive polymer exhibits a better anti-tumor efficacy than PTX in NPs containing ROS-non-sensitive polymer, free PTX or Abraxane® (nab-PTX). The biodistribution revealed that ROS-sensitive NPs exhibit retention in liver, spleen and lungs, suggesting a potential to target cancer metastasizing to these organs. Finally, we demonstrated a correlation between infiltrated macrophage subsets and treatment efficacy, possibly contributing to the efficient anti-tumor effects. CONCLUSION: Treatment with ROS-sensitive NPs containing PTX gave an improved therapeutic effect in HeLa xenografts than their counterpart, free PTX or nab-PTX. Our data revealed a correlation between macrophage infiltration and efficiency of the different antitumor treatments, as the most effective NPs resulted in the highest infiltration of the anti-tumorigenic M1 macrophages.

• Klíčová slova
• ROS-sensitive nanoparticles, macrophage infiltration, paclitaxel, reactive oxygen species, treatment efficacy,
• MeSH
• albuminy farmakologie   terapeutické užití   MeSH
• HeLa buňky MeSH
• hydrodynamika MeSH
• lidé MeSH
• makrofágy účinky léků   metabolismus   MeSH
• myši nahé MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• nanočástice terapeutické užití   MeSH
• paclitaxel farmakologie   terapeutické užití   MeSH
• paklitaxel vázaný na albumin terapeutické užití   MeSH
• polymery chemie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• tkáňová distribuce účinky léků   MeSH
• velikost částic MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 130-nm albumin-bound paclitaxel MeSH Prohlížeč
• albuminy MeSH
• paclitaxel MeSH
• paklitaxel vázaný na albumin MeSH
• polymery MeSH
• reaktivní formy kyslíku MeSH