Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow

Sobczynski, Daniel J.; Eniola‐Adefeso, Omolola

doi:10.1016/j.actbio.2016.10.023

Cited by 20 publications

(24 citation statements)

References 58 publications

(95 reference statements)

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“…Flow through the chamber was initiated via a programmable syringe pump. Before the flow assays, particles were incubated in plasma in a similar manner as previously described in Sobczynski and Eniola‐Adefeso, with a few key differences. Prior studies with PLGA particles have shown that after ≥5 min of exposure to 100% (i.e., undiluted) plasma, the extent of the adhesion reduction was saturated with no additional reduction observed up to 60 min incubation time .…”

Section: Methodsmentioning

confidence: 99%

“…Since the depletion kits limited the amount of depleted plasma available, incubation of diluted plasma was employed, and particles were incubated for ∼1 hr (Supporting Information Figure S1). The 1 hr incubation time with 25% plasma was chosen here since similar levels of adhesion reduction were achieved with this condition, as compared to ≥5 min 100% plasma incubation, which represents the physiological scenario in vivo. Moreover, a recent study by Tenzer et al observed that a protein corona is established within 1 min of plasma exposure and that changes beyond this time, up to 4 hr, occurs only in the amount and not the types of bound proteins.…”

Section: Methodsmentioning

confidence: 99%

“…Particles were incubated in the following media: 25%(vol/vol) native plasma, 25%(vol/vol) IgG‐depleted plasma, 25%(vol/vol) Igs‐depleted plasma (with and without Iso‐IgG, Iso‐IgA, and Purified‐IgM), and PBS. Particles were fluorescently labeled with biotin‐PE and reconstituted in a red blood cells (RBCs)‐in‐viscous buffer (VB; with viscosity matching that of human plasma and consisted of PBS++ 1%(wt/vol) BSA and 1.4%(wt/vol) dextran) medium as previously described . The hematocrit was fixed to 38%(vol/vol) for all experiments.…”

Section: Methodsmentioning

confidence: 99%

“…More recently, the plasma protein corona is reported to significantly affect the vascular wall adhesion efficiency of polymeric NPs . Specifically, NP targeting efficiency to cells or reactive substrates is found to be completely lost (up to 99% reduction) when exposed to plasma or serum, despite a high density of polyethylene glycol coating (PEG) coating on the particle surface .…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, NP targeting efficiency to cells or reactive substrates is found to be completely lost (up to 99% reduction) when exposed to plasma or serum, despite a high density of polyethylene glycol coating (PEG) coating on the particle surface . These observations were attributed to the significant presence of immunoglobulins (Igs) in the corona formed on the NP surface, which prevents adhesive interaction of the targeting ligands with their corresponding cell or surface receptors . However, the precise role of individual Ig protein classes in this process has yet to be studied.…”

Section: Introductionmentioning

confidence: 99%

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IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

Sobczynski

Eniola‐Adefeso

2017

Bioengineering & Transla Med

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The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic‐co‐glycolic) acid (PLGA)‐based vascular‐targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano‐sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re‐addition of IgA or IgM to the Igs‐depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40–70% reduction relative to particles with an Igs‐deficient corona. However, re‐addition of a high concentration of IgG to the Igs‐depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre‐coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

Sobczynski

Eniola‐Adefeso

2017

Bioengineering & Transla Med

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PLGA's Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery

Sheffey

Siew

Tanner

et al. 2022

Adv Healthcare Materials

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Numerous human disorders can benefit from targeted, intravenous (IV) drug delivery. Polymeric nanoparticles have been designed to undergo systemic circulation and deliver their therapeutic cargo to target sites in a controlled manner. Poly(lactic-co-glycolic) acid (PLGA) is a particularly promising biomaterial for designing intravenous drug carriers due to its biocompatibility, biodegradability, and history of clinical success across other routes of administration. Despite these merits, PLGA remains markedly absent in clinically approved IV drug delivery formulations. A prominent factor in PLGA particles' inability to succeed intravenously may lie in the hydrophobic character of the polyester, leading to the adsorption of serum proteins (i.e., opsonization) and a cascade of events that end in their premature clearance from the bloodstream. PEGylation, or surface-attached polyethylene glycol chains, is a common strategy for shielding particles from opsonization. Polyethylene glycol (PEG) continues to be regarded as the ultimate "stealth" solution despite the lack of clinical progress of PEGylated PLGA carriers. This review reflects on some of the reasons for the clinical failure of PLGA, particularly the drawbacks of PEGylation, and highlights alternative surface coatings on PLGA particles. Ultimately, a new approach will be needed to harness the potential of PLGA nanoparticles and allow their widespread clinical adoption.

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Biomolecular Corona Associated with Nanostructures: The Potentially Disruptive Role of Raman Microscopy

Battaglini

Gümüş

Ciofani

2021

Adv Materials Technologies

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investigating the use of nanomaterials within living organisms. When a nanoparticle (NP) encounters biological molecules such as proteins, lipids, nucleic acids, or polysaccharides, it tends to adsorb these molecules on its surface due to electrostatic, hydrophobic, or other forms of interactions between the molecules and the surface of the NP. [1][2][3][4] Depending on their abundance and affinity, proteins and other molecules may form a hard corona that consists of tightly bounded proteins on the surface, or a soft corona, which indicates a second layer of proteins that are loosely attached to the proteins of the hard corona. [4] The composition of the soft corona changes over time according to the environmental conditions, and so the biological identity of nanostructures is usually, but not always, determined by the hard corona. This can be both advantageous and disadvantageous to the application of NPs. Some studies have focused on preventing biomolecular corona (BC) formation, as this may change the size and surface properties, hinder modifications on the surface, and cause the rapid detection and clearance of NPs by the immune system. [5,6] However, BCs can be exploited or even altered, in order to be made beneficial for targeting purposes as they can enable specific cells to more easily recognize NPs and may lead to a reduction in their toxicity. [7,8] A wide range of techniques have been used in BC studies, such as dynamic light scattering (DLS), [9] sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), mass spectrometry (MS)-based approaches, [10][11][12][13][14][15][16][17][18][19][20][21] UV/vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), [22] atomic force microscopy (AFM), [23] scanning electron microscopy (SEM), [24][25][26][27] transmission electronic microscopy (TEM), [23] and circular dichroism spectroscopy (CD). [28] Various information (size, surface properties, morphology, structure, etc.) about BCs can be obtained through these methods. Many techniques have been applied in BC studies, which can be divided into microscopybased approaches that use direct imaging of the sample, and indirect techniques. Microscopy techniques can provide information about corona composition and shape with a spatial resolution up to the dimension scale of single protein molecules, but they are limited by the requirement for staining or extensive sample preparation. Indirect techniques can provide extensive information about BC-nanostructure interactions and properties, but typically have a limited resolution and so cannot analyze the BC at the level of single nanostructures. Other emerging

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Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow

Cited by 20 publications

References 58 publications

IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

PLGA's Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery

Biomolecular Corona Associated with Nanostructures: The Potentially Disruptive Role of Raman Microscopy

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