"All-in-one" multifunctional nanomaterials, which can be visualized simultaneously by several imaging techniques, are required for the efficient diagnosis and treatment of many serious diseases. This report addresses the design and synthesis of upconversion magnetic NaGdF4:Yb3+/Er3+(Tm3+) nanoparticles by an oleic acid-stabilized high-temperature coprecipitation of lanthanide precursors in octadec-1-ene. The nanoparticles, which emit visible or UV light under near-infrared (NIR) irradiation, were modified by in-house synthesized PEG-neridronate to facilitate their dispersibility and colloidal stability in water and bioanalytically relevant phosphate buffered saline (PBS). The cytotoxicity of the nanoparticles was determined using HeLa cells and human fibroblasts (HF). Subsequently, the particles were modified by Bolton-Hunter-neridronate and radiolabeled by 125I to monitor their biodistribution in mice using single-photon emission computed tomography (SPECT). The upconversion and the paramagnetic properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles were evaluated by photoluminescence, magnetic resonance (MR) relaxometry, and magnetic resonance imaging (MRI) with 1 T and 4.7 T preclinical scanners. MRI data were obtained on phantoms with different particle concentrations and during pilot long-time in vivo observations of a mouse model. The biological and physicochemical properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles make them promising as a trimodal optical/MRI/SPECT bioimaging and theranostic nanoprobe for experimental medicine.

• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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.

• Keywords
• ROS-sensitive nanoparticles, macrophage infiltration, paclitaxel, reactive oxygen species, treatment efficacy,
• MeSH
• Albumins pharmacology   therapeutic use   MeSH
• HeLa Cells MeSH
• Hydrodynamics MeSH
• Humans MeSH
• Macrophages drug effects   metabolism   MeSH
• Mice, Nude MeSH
• Cell Line, Tumor MeSH
• Neoplasms drug therapy   MeSH
• Nanoparticles therapeutic use   MeSH
• Paclitaxel pharmacology   therapeutic use   MeSH
• Albumin-Bound Paclitaxel therapeutic use   MeSH
• Polymers chemistry   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Tissue Distribution drug effects   MeSH
• Particle Size MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 130-nm albumin-bound paclitaxel MeSH Browser
• Albumins MeSH
• Paclitaxel MeSH
• Albumin-Bound Paclitaxel MeSH
• Polymers MeSH
• Reactive Oxygen Species MeSH

In the last half-century, the development of biodegradable polyesters for biomedical applications has advanced significantly. Biodegradable polyester materials containing external stimuli-sensitive linkages are favored in the development of therapeutic devices for pharmacological applications such as delivery vehicles for controlled/sustained drug release. These selectively biodegradable polyesters degrade after particular external stimulus (e.g., pH or redox potential change or the presence of certain enzymes). This review outlines the current development of biodegradable synthetic polyesters materials able to undergo hydrolytic or enzymatic degradation for various biomedical applications, including tissue engineering, temporary implants, wound healing and drug delivery.

• Keywords
• biodegradability, drug delivery, medical application, polycondensation, polyester, ring-opening, stimuli-sensitive,
• Publication type
• Journal Article MeSH
• Review MeSH