Monitoring drug nanocarriers in human blood by near-infrared fluorescence correlation spectroscopy

Negwer, Inka; Best, A.; Schinnerer, Meike; Schäfer, Olga; Capelôa, Leon; Wagner, Manfred; Schmidt, Manfred; Mailänder, Volker; Helm, Mark; Barz, Matthias; Butt, Hans‐Jürgen; Koynov, Kaloian

doi:10.1038/s41467-018-07755-0

Cited by 63 publications

(66 citation statements)

References 52 publications

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“…This low amount of enriched proteins validates the absence of—what is usually termed as—a hard protein corona on these NPs. For pSar‐NPs this is also in line with the FCS study in full blood by Negwer et al [ 42 ]…”

Section: Resultssupporting

confidence: 88%

“…[ 40,41 ] In addition, it was recently demonstrated that the pSar based nanoparticles maintain their diffusion coefficient and thus hydrodynamic radius even in full human blood. [ 42 ] From the chemical side PEG and pSar follow the Whitesides Rules for protein resistant materials, as they are hydrophilic and only weak H‐bond acceptors without a net charge and H‐bond donor properties. [ 43 ] Moreover, pSar and PEG possess identical solution properties in aqueous solution.…”

Section: Introductionmentioning

confidence: 99%

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Polymeric Nanoparticles with Neglectable Protein Corona

Alberg

Krämer

Schinnerer

et al. 2020

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with cells, [10] can shield recognition units, [15] but its role for biodistribution and circulation is still far from well understood. [8,16] Except for liposomes, other types of nano-sized drug delivery systems, such as polymeric micelles or more complex polymer constructs like cylindrical polymer brushes [17] have been so far hardly investigated with respect to protein corona formation (for comparison between the structures of these nanoparticles and the colloidal nanoparticles discussed above, see Figures S1 and S2 in the Supporting Information). [8,[18][19][20] However, the former are interesting, since polymeric micelles are in advanced stages of clinical testing (e.g., CPC634 (phase II) [21] and NC-6004 Nanoplatin (phase III) [22] ).To evaluate the formation of a protein corona, separation of the nanoparticle-protein-complex from unbound proteins used for incubation or upon in vivo exposure becomes a necessity. The isolation of incubated nanoparticles (colloids and inorganic nanoparticles) from unbound proteins was mainly performed by centrifugation, which is a separation method based on differences in density. [23] Thus, this method allows only the purification of nanoparticles with a higher density but can hardly be used for low density particles, such as polymeric micelles and polymer brushes. [24] Only recently, size exclusion techniques such as size exclusion chromatography and asymmetrical flow field-flow fractionation (AF4) have been employed for this purpose. [19,25,26] AF4 is a separation technique, which can be applied for the separation of particle and protein mixtures in the size range between 1 nm and 1 µm. [27,28] It consists of a separation channel with a flow gradient in which the particles are separated by an additional vertical force field depending on their diffusion coefficient. [29,30] During an AF4 measurement, the injected particles are pushed by the vertical cross flow toward the membrane at the bottom of the channel. Due to Brownian motion, the particles are diffusing back into the middle of the channel. Since smaller particles are faster than larger ones (because of their higher diffusion coefficient), they are concentrating faster in the middle, thus eluting first through the channel outlet. In contrast to conventional size exclusion chromatography, in AF4 the contact to the interface and the shear forces are substantially reduced, which leads to very mild separation conditions, minimizing perturbations of a potential protein corona. [26,31] Based on this method, Landfester and coworkers recently fully characterized the protein corona of Lutensol AT50-coated polystyrene nanoparticles and PEG functionalized liposomes, identifying all adsorbed proteins. [19,26] Here, we present a purification procedure based on AF4 for the separation of smaller polymeric architectures (R h : 20-30 nm) that are hardly separable by centrifugation. We isolated polymeric nanoparticles from unbound blood plasma components and characterized them by dynamic light scattering, gel electrophoresis and mass s...

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Polymeric Nanoparticles with Neglectable Protein Corona

Alberg

Krämer

Schinnerer

et al. 2020

Small

Self Cite

119

187

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“…Afterwards, excitation with high‐intensity light can provide a highly localized “burst” of the cytotoxic species precisely at the desired sites. Moreover, the use of fluorescently labeled nanocarrier can be useful to gain insights into the delivery process . Two‐photon fluorescence microscopy represents a valuable tool in this regard.…”

Section: Methodsmentioning

confidence: 99%

A Three‐Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two‐Photon Excitation with Near‐Infrared Light

Fraix

Kirejev

Fenyvesi

et al. 2019

Chemistry A European J

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A supramolecular nanoassembly, of about 30 nm in diameter, that consists of a green‐fluorescent, β‐cyclodextrin‐based, branched polymer co‐encapsulating a red‐emitting singlet oxygen (1O2) photosensitizer and a nitric oxide (NO) photoreleaser, which comprises a blue fluorescent reporter, is here reported. The system exhibits “five‐in‐one” photofunctionalities. All components can be simultaneously excited in the phototherapeutic window with two‐photons by using near‐infrared light at 740 nm and despite their close proximity, behave as independent units. This allows for their in vitro visualization in carcinoma cancer cells, due to their distinct green, red, and blue fluorescence, and for the production of both cytotoxic 1O2 and biofunctional NO.

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“…Klein et al recently reported on the ability of polysarcosine to shield siRNA lipoplexes and analyzed the in vivo stability and biodistribution while Koynov and coworkers demonstrated that pSar shielded nanoparticle maintain their size even in human blood. [39,40] Moreover, the unimolecular character of star polymers seems highly beneficial for extracellular stability and results in stable carrier systems without elaborated cross-linking methods. On the one hand, this may prevent the premature release of the cargo in circulation.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

Holm

Schwiertz

Weber

et al. 2019

Macromolecular Bioscience

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RNA interference provides enormous potential for the treatment of several diseases, including cancer. Nevertheless, successful therapies based on siRNA require overcoming various challenges, such as poor pharmacokinetic characteristics of the small RNA molecule and inefficient cytosolic accumulation. In this respect, the development of functional siRNA carrier systems is a major task in biomedical research. To provide such a desired system, the synthesis of 3‐arm and 6‐arm PeptoStars is aimed for. The different branched polypept(o)idic architectures share a stealth‐like polysarcosine corona for efficient shielding and a multifunctional polylysine core, which can be independently varied in size and functionality for siRNA complexation‐, transport and intra cellular release. The special feature of star‐like polypept(o)ides is in their uniform small size (<20 nm) and a core–shell structure, which implies a high stability and stealth‐like properties and thus, they may combine long circulation times and a deep penetration of cancerous tissue. Initial toxicity and complement studies demonstrate well tolerated cationic PeptoStars with high complexation capability toward siRNA (N/P ratio up to 3:1), which can lead to potent RNAi for optimized systems. Here, the synthetic development of 3‐arm and 6‐arm polypept(o)idic star polymers, their modification with endosomolytic moieties, and first in vitro insights on RNA interference are reported on.

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Monitoring drug nanocarriers in human blood by near-infrared fluorescence correlation spectroscopy

Cited by 63 publications

References 52 publications

Polymeric Nanoparticles with Neglectable Protein Corona

Polymeric Nanoparticles with Neglectable Protein Corona

A Three‐Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two‐Photon Excitation with Near‐Infrared Light

Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

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