BODIPY-loaded polymer nanoparticles: chemical structure of cargo defines leakage from nanocarrier in living cells

Trofymchuk, Kateryna; Valančiūnaitė, Jurga; Andreiuk, Bohdan; Reisch, Andreas; Collot, Mayeul; Klymchenko, Andrey S.

doi:10.1039/c8tb02781a

Cited by 49 publications

(50 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…71 Presence of bulky groups has shown to improve the brightness of polymeric NPs. 67,[72][73][74] However, so far BODIPY dyes or other high-performance fluorescent dyes had not been used for preparing single-chain fluorescent NPs.…”

mentioning

confidence: 99%

Stealth and Bright Monomolecular Fluorescent Organic Nanoparticles Based on Folded Amphiphilic Polymer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Fluorescent nanoparticles (NPs), owing to their superior brightness, are an attractive alternative to organic dyes. However, their cellular applications remain limited because of their large size, poor homogeneity and non-specific interactions in biological media. Herein, we propose a concept of monomolecular fluorescent organic nanoparticle of high brightness and very small size (10-14 nm) built of a single amphiphilic polymer bearing specially designed fluorescent dyes. We found that high PEGylation of poly(maleic anhydride-alt-1-octadecene (PMAO) favors a single-chain polymer folding into monomolecular stealth NPs with highly reduced non-specific interactions with live cells. To ensure high stability of our NPs, the fluorophores (BODIPYs) are covalently linked to the polymer through an optimized linker. Among tested linkers of different lengths and polarity, short medium-polar linker favoring location of the dyes at NPs interface ensures good 2 fluorescence quantum yield and small particle size. The fluorescence brightness of these NPs has been dramatically enhanced by increasing the bulkiness of the BODIPY dyes that prevents their H-aggregation, reaching 2,500,000 M -1 cm -1 (extinction coefficient × quantum yield).Fluorescence microscopy revealed that the single-particle brightness of these NPs is ~5-fold higher than that of QDot-585 using the same excitation wavelength (532 nm). Finally, when microinjected inside cells, these small and stealth NPs (10-nm diameter) distribute more evenly than 20-nm QDots inside the cytosol, showing similar spreading as a fluorescent protein. Thus, the developed monomolecular NPs, owing to small size and stealth properties, are artificial analogues of fluorescent proteins, surpassing the latter >50-fold in terms of brightness.

show abstract

mentioning

confidence: 99%

Stealth and Bright Monomolecular Fluorescent Organic Nanoparticles Based on Folded Amphiphilic Polymer

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…For fluorescent labeling, two different fluorescent dyes with visible (BODIPY™ FL C 12 , green, 510 nm) and near-infrared (VivoTag-S 750, red, 750 nm) emission wavelengths were used. BODIPYs are low-polarity dyes with stable fluorescence emission properties [56] and are commonly used in fluorescence detection and photodynamic therapy applications [57]. VivoTag-S 750 is a near-infrared emitting (NIR) fluorochrome extensively used for in vivo imaging applications [58,59].…”

Section: Resultsmentioning

confidence: 99%

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

et al. 2019

View full text Add to dashboard Cite

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

show abstract

“…For fluorescent labelling, two different fluorescent dyes with visible (BODIPY™ FL C12, green, 510 nm) and near-infrared (VivoTag-S 750, red, 750 nm) emission wavelengths were used. BODIPYs are low-polarity dyes with stable fluorescence emission properties [56] and are commonly used in fluorescence detection and photodynamic therapy applications [57]. VivoTag-S 750 is a near-infrared emitting (NIR) fluorochrome extensively used for in vivo imaging applications [58,59].…”

Section: Results and Discussion: Preparation Of Particlesmentioning

confidence: 99%

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Operti¹,

Dölen²,

Keulen³

et al. 2019

Preprint

View full text Add to dashboard Cite

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

show abstract

BODIPY-loaded polymer nanoparticles: chemical structure of cargo defines leakage from nanocarrier in living cells

Abstract: Hydrophobicity of a fluorescent cargo loaded into PLGA nanoparticles is crucial for minimizing its leakage in biological media.

Cited by 49 publications

References 83 publications

Stealth and Bright Monomolecular Fluorescent Organic Nanoparticles Based on Folded Amphiphilic Polymer

Stealth and Bright Monomolecular Fluorescent Organic Nanoparticles Based on Folded Amphiphilic Polymer

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Contact Info

Product

Resources

About