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Conjugated polymer nanoparticles (CPN) have gathered interest recently because of their ability to exhibit a high fluorescence. As such they have become an interesting material for fluorescent probes in biological fluorescence imaging applications for small animal cell cultures.
However, CPNs are generally too large for human use and has limited their use in real-world applications because of their lack of degradation and excretion abilities. However, a team of Researchers from Germany have created conjugated polymer nanoparticles using imidazole units which show a much higher real-world application potential due to their ability to be easily removed from the body.
Conjugated polymer nanoparticles (CPNs) have been touted as a great material for staining cells and tissues across various fluorescence-based biomedical imaging techniques, such as microscopy and tomography.
CPNs have been found to possess a great potential due to their excellent properties. Firstly, CPNs are hydrophobic and chemically inert in nature allowing them to be taken up by the cells easily with a low cytotoxicity. The nanoparticles also possess π-conjugated systems which produce a strong fluorescence that is highly tuneable across the visible and near infrared (NIR) color spectrum.
CPNs are mostly composed of semiconducting materials and are highly photostable for long periods of time. They have also shown great potential as photoacoustic contrast agents and for image-guided photodynamic and photothermal therapy.
CPNs also have the ability to be functionalized with biological recognition moieties at their surface, making them applicable as labelers for biological imaging techniques.
Currently direct polymerization techniques have yielded nanoparticles of 200 to 2 µm in size and post-polymerization techniques have been able to reduce this to around 50 nm. However, the major challenge facing this field is in the production of particles which can fit through renal cavities and be expelled from the body. This issue is significant because the renal clearance of a human body is around 5-6 nm. So, whilst they currently show great potential, they can’t be used in real-world imaging applications due to their inability to be removed from the body.
Because of the size issue, the Researchers from Germany have adopted a different way of degrading the nanoparticles. The Researchers have created CPNs based around imidazole units which can be degraded by macrophages in the bloodstream with no requirement to be directly passed through the small renal channels. The Researchers fully conjugated the polymer chains along their backbone(s).
The Researchers characterized and tested the biodegradable CPNs using a range of techniques, including dynamic light scattering (DLS, Zetasizer Nano ZS, Malvern Instruments), gel permeation—size exclusion chromatography (SEC, Jasco PU-2080plus Pump, Jasco RI-2031plus refractive index detector, Polymer Laboratories PL-ELS-1000 light scattering detector), mass spectrometry (SSQ7000, Finnigan), electrospray ionisation mass spectrometry (ESI-MS, LCQ Deca XP plus, ThermoFinnigan), confocal microscopy (TCS SP8, Leica), photoluminescence spectroscopy (Jobin-Yvon FluoroMax- 4 spectrofluorometer, Horiba), UV-Visible spectroscopy (UV-Vis, Cary 50, Varian) and scanning electron microscopy (SEM, S-4800, Hitachi). Kaiser test, cytotoxicity and microscopic macrophage degradation studies were also performed by the Researchers.
The nanoparticles were found to decompose when they were exposed to reactive oxygen species (ROS), such as hydrogen peroxide. This was an important finding because activated macrophages generate ROS, allowing for the nanoparticles to be potentially broken down in the body through bio-degradative oxidation mechanisms.
The degradation mechanism, be it from macrophages or other ROS, proceeded through an induced scission of the conjugated polymer backbone at the imidazole unit using the ROS as ‘scissor molecules’. The mechanism led to a complete decomposition of the nanoparticles into water soluble, low-weight molecular fragments.
The particles also possessed the ability for surface functionalization, which is useful for many biological targeting approaches, including turning the nanoparticles into bio-medical homing devices for targeted delivery, and for labeling purposes for specific biological recognition motifs. The conjugated polymer particles also provided a greater optical gain than degradable inorganic materials because of their dense luminophore packing.
Future work needs to be undertaken before these nanoparticles can be used in real-world applications. The Researchers first need to work out if the degradation of the particles is sufficient in-vivo. The Researchers also wish to and to see if the concept of releasable drug delivery using these nanoparticles is possible, and if so, if the oxidative degradation mechanism extends to nanoparticles that can carry and release drugs, by releasing them using macrophage ROS degradation approaches.
Whilst work is still needed, the research has opened the possibility of using conjugated polymer particles for many medical fields, such as imaging, drug-delivery and theranostics, and presents a major stepping stone for realizing such materials in commercially viable real-world applications.
Image Credit:
anyaivanova/ Shutterstock.com
Source:
“Bio-degradable highly fluorescent conjugated polymer nanoparticles for bio-medical imaging applications”- Repenko T., et al, Nature Communications, 2017, DOI: 10.1038/s41467-017-00545-0
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