Surface Chemistry of Photoluminescent F8BT Conjugated Polymer Nanoparticles Determines Protein Corona Formation and Internalization by Phagocytic Cells

Abstract

Conjugated polymer nanoparticles are being developed for a variety of diagnostic and theranostic applications. The conjugated polymer, F8BT, a polyfluorene derivative, was used as a model system to examine the biological behavior of conjugated polymer nanoparticle formulations stabilized with ionic (sodium dodecyl sulfate; F8BT-SDS; ∼207 nm; -31 mV) and nonionic (pegylated 12-hydroxystearate; F8BT-PEG; ∼175 nm; -5 mV) surfactants, and compared with polystyrene nanoparticles of a similar size (PS200; ∼217 nm; -40 mV). F8BT nanoparticles were as hydrophobic as PS200 (hydrophobic interaction chromatography index value: 0.96) and showed evidence of protein corona formation after incubation with serum-containing medium; however, unlike polystyrene, F8BT nanoparticles did not enrich specific proteins onto the nanoparticle surface. J774A.1 macrophage cells internalized approximately ∼20% and ∼60% of the F8BT-SDS and PS200 delivered dose (calculated by the ISDD model) in serum-supplemented and serum-free conditions, respectively, while cell association of F8BT-PEG was minimal (<5% of the delivered dose). F8BT-PEG, however, was more cytotoxic (IC50 4.5 μg cm(-2)) than F8BT-SDS or PS200. The study results highlight that F8BT surface chemistry influences the composition of the protein corona, while the properties of the conjugated polymer nanoparticle surfactant stabilizer used determine particle internalization and biocompatibility profile.

Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device

“…While CN-PPV self-assembles and formed CPNs in the absence of amphiphilic stabilising molecules (100% CN-PPV formulation), the highly hydrophobic F8BT forms nanoparticles only in the presence of surfactants, and very low batch yields were obtained previously (<30%) 26 . The incorporation of conjugated polymers within a matrix of the amphiphilic PEG-PLGA diblock copolymers was found to be a successful strategy to improve product yields of these systems.…”

“…The red or near-infrared luminescence emission 16 of CN-PPV-based materials led to their use in cell labelling [17][18][19] , protein The material composition of CPNs influences their properties in biological fluids and cell culture media. For example, our earlier work has demonstrated that the type of surfactants used for nanoparticle assembly plays an important role in determining cellular uptake, biocompatibility and protein corona formation 26 (protein adsorption to nanoparticle surface after exposure to biological fluids 27 ). Surfactants containing poly(ethylene glycol) (PEG) are commonly used for steric stabilization since they form a hydrophilic layer on the surface of the nanoparticles that prevents interactions with blood components 28 .…”

PPV-Based Conjugated Polymer Nanoparticles as a Versatile Bioimaging Probe: A Closer Look at the Inherent Optical Properties and Nanoparticle–Cell Interactions

“…With the inherent conjugated backbone, the latter have stipulated large interest outside the field of flexible electronics due to their excellent optical properties -fluorescence brightness, ideal photostability, fast radiative rate and nonblinking behavior -together with biocompatibility for use in the bioimaging field. [15][16][17] Among the different polymers poly(p-phenylene vinylene) (PPV), a pioneer material for the first organic light emitting diode (oLED) and since then one of the most thoroughly studied conjugated polymers, is of great interest owing to its reliable synthesis routes in combination with design flexibility offered by the recent control methodologies for realizing tailor-made functional PPVs, simple scale up potential and their well-known photophysical properties. [18][19][20] Though PPV derivatives are highly interesting as a fluorophore, their interaction with biological environments and performance as bioimaging probe have not yet been fully explored to date, the research emphasis laying predominantly on synthesis routes and inherent material characteristics.…”

“…[25][26] They are indispensable for attaching biomolecules to impart for instance target specificity or a stealth 5 effect. Instead of being forced to use complex and tedious post-synthesis methods in a later stadium or surface adsorbed surfactant molecules 15 , functionalized PPVs synthesized via the sulfinyl precursor route offer an elegant alternative to introduce surface functional groups. By employing such custom-made PPV-derivatives for the NP formulation, the synthetic identity of the NP based bioimaging probe can be fine-tuned to meet the set out conditions in the biological environment.…”

Silica passivated conjugated polymer nanoparticles for biological imaging applications

“…We have also studied the effect of surface chemistry of CPNs and how this affects uptake and internalisation in phagocytic cells 30 . We report the possibility of using silica to encapsulate a CP/pluronic micelle which is prepared using a modified bioinspired silification approach 31,32 .…”