Effect of nanoparticle size and PEGylation on the protein corona of PLGA nanoparticles

Partikel, Katrin; Korte, Robin; Stein, Nora C.; Mulac, Dennis; Herrmann, Fabian; Humpf, Hans‐Ulrich; Langer, Klaus

doi:10.1016/j.ejpb.2019.05.006

Cited by 127 publications

(103 citation statements)

References 51 publications

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“…It is worth mentioning that a 1-h incubation was reported to be enough for the formation of a stable hard corona of NPs; whereas similar amounts of adsorbed proteins were detected over a duration of 5 to 90 minutes. 7 For the protein quantification, a modified protocol of Partikel et al 33,34 was employed. Eight mg of NPs were hydrolyzed with 500 μL of 0.5 M sodium hydroxide for 15 min at 60 °C and 1200 rpm in a heating dry block (Eppendorf Thermomixer, Germany).…”

Section: Quantification Of the Nps' Pc By Bradford Assaymentioning

confidence: 99%

“…Absorbance was then monitored at 595 nm for the quantification of the adsorbed proteins and compared to a calibration curve of bovine serum albumin (BSA) in the range of 0.01-1 mg/mL. 33,34 For the calculation of the total amount of proteins adsorbed per surface area of NPs, density of 1.3 g/cm 3,35 and a spherical shape, as estimated in our previous work by the scanning electron microscopy (SEM), 30 were assumed.…”

Section: Quantification Of the Nps' Pc By Bradford Assaymentioning

confidence: 99%

“…For the medium control, SF or SR DMEM obtained from the cultures were diluted 100x with UPW. 33,34 Immunostaining for WBs was performed using the mouse monoclonal primary antibodies; Vitronectin 65/75 antibody (D-8), Complement protein 3 (C3), antibody (B-9), Clusterin-α Antibody (A-11), Annexin I Antibody (EH17a), Clathrin HC Antibody (TD.1) and Filamin 1 Antibody (E-3) (Santa Cruz, Germany), and an alkaline phosphatase conjugated anti-mouse secondary antibody (Promega, Germany) following a standard protocol in our lab. 36 Semi-quantification of the relative band intensities of WBs was performed using ImageJ 1.37c software (National Institutes of Health, NIH).…”

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confidence: 99%

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<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective</p>

Sebak

Gomaa

ElMeshad

et al. 2020

IJN

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Introduction Protein corona (PC) deposition on nanoparticles (NPs) in biological systems contributes to a great extent to NPs’ fates; their targeting potential, the interaction with different biological systems and the subsequent functions. PC – when properly tuned – can serve as a potential avenue for optimization of NPs’ use in cancer therapy. Methods Poly-lactic co-glycolic acid (PLGA)-based NPs exhibiting different physicochemical properties were fabricated and characterized. The PC makeup of these NPs were qualitatively and quantitatively analyzed by Western blot and Bradford assay, respectively. The effect of PC on the release of NPs’ cargos and the intracellular uptake into B16F10 melanoma cells has been studied. Results The composition of NPs (polymeric PLGA NPs vs lipid-polymer hybrid NPs) and the conjugation of an active targeting ligand (cRGDyk peptide) represented the major determinants of the PC makeup of NPs. The in vitro release of the loaded cargos from the NPs depended on the PC and the presence of serum proteins in the release medium. Higher cumulative release has been recorded in the presence of proteins in the case of peptide conjugated NPs, cNPs, while the unconjugated formulations, uNPs, showed an opposite pattern. NPs intracellular uptake studies revealed important roles of distinct serum and cellular proteins on the extent of NPs’ accumulation in melanoma cells. For example, the abundance of vitronectin (VN) protein from serum has been positively related to the intracellular accumulation of the NPs. Conclusion Careful engineering of nanocarriers can modulate the recruitment of some proteins suggesting a potential use for achieving endogenous targeting to overcome the current limitations of targeted delivery of chemotherapeutic agents.

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Section: Quantification Of the Nps' Pc By Bradford Assaymentioning

confidence: 99%

Section: Quantification Of the Nps' Pc By Bradford Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective</p>

Sebak

Gomaa

ElMeshad

et al. 2020

IJN

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“…In this context, it is important to understand the interactions occurring at the interface between NPs and biological fluids to predict the fate of injected NPs. It is commonly accepted that the interaction of the NPs and biological fluids is a consequence of several factors.NP size, shape, charge, or coating agents are critical [62][63][64][65][66][67][68][69], but the characteristics of the biological fluids are also very important (ionic strength, protein concentration, pH, and temperature) [70]. Once NPs are exposed to biological fluids, they interact with active biomolecules (mostly proteins, but also sugars, nucleic acids, and lipids) and PC is formed around them by the unspecific absorption of proteins on the surface of the NPs.…”

Section: Formation Of Protein Corona: Effect On Np-based Immunotherapymentioning

confidence: 99%

Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

Mikelez-Alonso

Aires

Cortajarena

2020

IJMS

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Immunotherapy has become a promising cancer therapy, improving the prognosis of patients with many different types of cancer and offering the possibility for long-term cancer remission. Nevertheless, some patients do not respond to these treatments and immunotherapy has shown some limitations, such as immune system resistance or limited bioavailability of the drug. Therefore, new strategies that include the use of nanoparticles (NPs) are emerging to enhance the efficacy of immunotherapies. NPs present very different pharmacokinetic and pharmacodynamic properties compared with free drugs and enable the use of lower doses of immune-stimulating molecules, minimizing their side effects. However, NPs face issues concerning stability in physiological conditions, protein corona (PC) formation, and accumulation in the target tissue. PC formation changes the physicochemical and biological properties of the NPs and in consequence their therapeutic effect. This review summarizes the recent advances in the study of the effects of PC formation in NP-based immunotherapy. PC formation has complex effects on immunotherapy since it can diminish (“immune blinding”) or enhance the immune response in an uncontrolled manner (“immune reactivity”). Here, future perspectives of the field including the latest advances towards the use of personalized protein corona in cancer immunotherapy are also discussed.

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“…This corona formation can thus disrupt all cell-selective targeting strategies. Current research activities focus on the prevention of corona formation, e.g., by the coupling of PEG molecules to the liposomes or other nanoparticles [65], although this may lead to other problems such as the accelerated blood clearance phenomenon (see above). Fundamental knowledge on processes that affect corona formation is lacking, but it is becoming clear that physio-chemical properties of the particle itself are an important factor [62,66].…”

Section: Nanoparticles As Drug Carriers To Hepatic Cells: Benefits Anmentioning

confidence: 99%

Innovative Nanotechnological Formulations to Reach the Hepatic Stellate Cell

Poelstra

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review Treatment of liver fibrosis benefits from hepatic stellate cell (HSC)-specific delivery. Since the description of first carrier to HSC, many developments have taken place in this area. The purpose is to give an overview of the different carriers and homing moieties that are available for HSC targeting and illustrate the opportunities and hurdles they provide. Recent Findings There is a growing number of homing devices to deliver drugs to HSC, and options to deliver siRNA to HSC have emerged. Other developments include controlling corona formation, development of linker technology, and design of theranostic approaches. We are on the eve of reaching the clinic with innovative HSC-specific compounds. Summary An overview of different core molecules is presented together with an overview of targeting strategies toward different receptors on HSC, providing a versatile toolbox. Many therapeutics, ranging from small chemical entities and proteins to RNAor DNA-modulating substances, have already been incorporated in these constructs in the recent years.

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Effect of nanoparticle size and PEGylation on the protein corona of PLGA nanoparticles

Cited by 127 publications

References 51 publications

<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective</p>

<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective</p>

Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

Innovative Nanotechnological Formulations to Reach the Hepatic Stellate Cell

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