Theranostic Approach for the Protein Corona of Polysaccharide Nanoparticles

Skaličková, Sylvie; Horký, Pavel; Mlejnková, Veronika; Skládanka, Jiří­; Hosnedlová, Božena; Ruttkay-Nedecký, Branislav; Fernandez, Carlos; Kizek, René

doi:10.1002/tcr.202000042

Cited by 9 publications

(9 citation statements)

References 112 publications

(173 reference statements)

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“…It is the complex NP-protein corona that interacts with the rest of the species in the biological system, so controlling this process is of paramount important to any biomedical application [15]. To control the nonspecific protein adsorption, the surface of the NPs are commonly passivated by fuctionalization with biocompatible polymers [16], such as poly(ethylene)glycol (PEG) [17], self-assembled monolayers (SAMS) [18,19], zwitterions [20,21], polysaccharides [22], peptoids [23][24][25], and thermoresponsive polymers [26,27]. The polymeric layer provides a repulsive steric barrier to proteins, limiting their adsorption [28,29].…”

Section: Introductionmentioning

confidence: 99%

Proteins Adsorbing onto Surface-Modified Nanoparticles: Effect of Surface Curvature, pH, and the Interplay of Polymers and Proteins Acid–Base Equilibrium

2022

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Protein adsorption onto nanomaterials is a process of vital significance and it is commonly controlled by functionalizing their surface with polymers. The efficiency of this strategy depends on the design parameters of the nanoconstruct. Although significant amount of work has been carried out on planar surfaces modified with different types of polymers, studies investigating the role of surface curvature are not as abundant. Here, we present a comprehensive and systematic study of the protein adsorption process, analyzing the effect of curvature and morphology, the grafting of polymer mixtures, the type of monomer (neutral, acidic, basic), the proteins in solution, and the conditions of the solution. The theoretical approach we employed is based on a molecular theory that allows to explicitly consider the acid–base reactions of the amino acids in the proteins and the monomers on the surface. The calculations showed that surface curvature modulates the molecular organization in space, but key variables are the bulk pH and salt concentration (in the millimolar range). When grafting the NP with acidic or basic polymers, the surface coating could disfavor or promote adsorption, depending on the solution’s conditions. When NPs are in contact with protein mixtures in solution, a nontrivial competitive adsorption process is observed. The calculations reflect the balance between molecular organization and chemical state of polymers and proteins, and how it is modulated by the curvature of the underlying surface.

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Section: Introductionmentioning

confidence: 99%

Proteins Adsorbing onto Surface-Modified Nanoparticles: Effect of Surface Curvature, pH, and the Interplay of Polymers and Proteins Acid–Base Equilibrium

2022

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“…It was proved that two distinct layers including loosely bound proteins (outer soft corona layer) and strongly attached proteins (inner hard corona layer) are generated around the NPs immediately after 30 s upon exposure to biofluids. To be specific, it is estimated that the frequency of protein collision to NPs is about 10 6 /s. − Notably, this phenomenon is an unavoidable event for any particle in the nano-size dimensions. The PC formation is more of a physical interaction rather than a chemical process.…”

Section: Introductionmentioning

confidence: 99%

“…Given that the type and nature of PC differ in pathological and physiological conditions, one can hypothesize that the PC that formed around NPs can possibly be one of the most important reasons for nano-based drug delivery system failure and translation into the clinical setting. − As a matter of fact, providing in-depth knowledge about the real behavior of decorated NPs with certain ligands, the possibility of PC formation, and their reciprocal interactions can help us gain the best decision-making on their usage in a context-dependent manner. Therefore, PC formation can be considered as the most important factor, which dictates the NP biodistribution, toxicity, pharmacokinetics, and fate in the body. ,, It seems the evaluation of well-known ligands, which in some cases are in the clinical trial on recruiting for PC formation, is an urgent need to improve targeting efficiency in pathological conditions. Folic acid (FA) is touted as a promising ligand and delivery route for phase II clinical trials in patients with solid tumors .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PC formation can be considered as the most important factor, which dictates the NP biodistribution, toxicity, pharmacokinetics, and fate in the body. 9,35,36 It seems the evaluation of well-known ligands, which in some cases are in the clinical trial on recruiting for PC formation, is an urgent need to improve targeting efficiency in pathological conditions. Folic acid (FA) is touted as a promising ligand and delivery route for phase II clinical trials in patients with solid tumors.…”

Section: ■ Introductionmentioning

confidence: 99%

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Unraveling the Effect of Breast Cancer Patients’ Plasma on the Targeting Ability of Folic Acid-Modified Chitosan Nanoparticles

et al. 2021

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The formation of protein corona (PC) around nanoparticles (NPs) has been reported inside biological conditions. This effect can alter delivery capacity toward the targeted tissues. Here, we synthesized folic acid-modified chitosan NPs (FA-CS NPs) using different concentrations of folic acid (5, 10, and 20%). FA-CS NPs were exposed to plasmas of breast cancer patients and healthy donors to evaluate the possibility of PC formation. We also monitored uptake efficiency in in vitro conditions after incubation with human breast cancer cell line MDA-MB-231 and monocyte/macrophage-like Raw264.7 cells. Data showed that the formation of PC around FA-CS NPs can change physicochemical properties coincided with the rise in NP size and negative surface charge. SDS-PAGE electrophoresis revealed differences in the type and content rate of plasma proteins attached to NP surface in a personalized manner. Based on MTT data, the formation of PC around NPs did not exert cytotoxic effects on MDA-MB-231 cells while this phenomenon reduced uptake rate. Fluorescence imaging and flow cytometry analyses revealed reduced cellular internalization rate in NPs exposed to patients' plasma compared to the control group. In contrast to breast MDA-MB-231 cells, Raw264.7 cells efficiently adsorbed the bare and PC-coated NPs from both sources, indicating the involvement of ligand−receptor-dependent and independent cellular engulfment. These data showed that the PC formed on the FA-CS NPs is entirely different in breast cancer patients and healthy counterparts. PC derived from patients' plasma almost abolishes the targeting efficiency of FA-CS NPs even in different mechanisms, while this behavior was not shown in the control group. Surprisingly, Raw264.7 cells strongly adsorbed the PC-coated NPs, especially when these particles were in the presence of patients' sera. It is strongly suggested that the formation of PC around can affect delivering capacity of FA-CS NPs to cancer cells. It seems that the PC-coated FA-CS NPs can be used as an efficient delivery strategy for the transfer of specific biomolecules in immune system disorders.

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“…Understanding how NPs interact with the biological milieu is key to develop suitable tumour targeting drug delivery systems [29]. On this regard, several reviews focusing on the improvement of the design of nanocarriers [23,[30][31][32] along with analysing the effect of protein corona on theragnostic applications of nanocarriers [33] have been recently published. Especially, a recent review shed lights on the factors, such as physico-chemical properties that affect the formation of protein corona on CtNPs and its impact on drug delivery applications [34].…”

mentioning

confidence: 99%