Dataset Information

Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS.

ABSTRACT: Because cystoscopy is expensive and invasive, a new method of detecting non-invasive muscular bladder cancer (NMIBC) is needed. This study aims to identify potential serum protein markers for NMIBC to improve diagnosis and to find treatment approaches that avoid disease progression to a life-threatening phenotype (muscle-invasive bladder cancer, MIBC). Here, silver nanoparticles (AgNPs, 9.73 ± 1.70 nm) as a scavenging device together with sequential window acquisition of all theoretical mass spectra (SWATH-MS) were used to quantitatively analyze the blood serum protein alterations in two NMIBC subtypes, T1 and Ta, and they were compared to normal samples (HC). NMIBC's analysis of serum samples identified three major groups of proteins, the relative content of which is different from the HC content: proteins implicated in the complement and coagulation cascade pathways and apolipoproteins. In conclusion, many biomarker proteins were identified that merit further examination to validate their useful significance and utility within the clinical management of NMIBC patients.

SUBMITTER: Gomez BB

PROVIDER: S-EPMC8467878 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS.

Gómez Benito Blanco BB López-Cortés Rubén R Casas-Nebra Francisco Javier FJ Vázquez-Estévez Sergio S Pérez-Fentes Daniel D Chantada-Vázquez María Del Pilar MDP Bravo Susana B SB Núñez Cristina C

Nanomaterials (Basel, Switzerland) 20210913 9

Because cystoscopy is expensive and invasive, a new method of detecting non-invasive muscular bladder cancer (NMIBC) is needed. This study aims to identify potential serum protein markers for NMIBC to improve diagnosis and to find treatment approaches that avoid disease progression to a life-threatening phenotype (muscle-invasive bladder cancer, MIBC). Here, silver nanoparticles (AgNPs, 9.73 ± 1.70 nm) as a scavenging device together with sequential window acquisition of all theoretical mass spe ...[more]

PMID: 34578700

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Project description:Background: When nanoparticles (NPs) are applied into a biological fluid, such as blood, proteins bind rapidly to their surface forming a so-called "protein corona". These proteins are strongly attached to the NP surface and confers them a new biological identity that is crucial for the biological response in terms of body biodistribution, cellular uptake, and toxicity. The corona is dynamic in nature and it is well known that the composition varies in dependence of the physicochemical properties of the NPs. In the present study we investigated the protein corona that forms around poly(lactide-co-glycolide) (PLGA) NPs at different serum concentrations using two substantially different serum types, namely fetal bovine serum (FBS) and human serum. The corona was characterized by means of sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), Bradford protein assay, zeta potential measurements, and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Additionally, the time-dependent cell interaction of PLGA NPs in the absence or presence of a preformed protein corona was assessed by in vitro incubation experiments with the human liver cancer cell line HepG2. Results: Our data revealed that the physiological environment critically affects the protein adsorption on PLGA NPs with significant impact on the NP-cell interaction. Under comparable conditions the protein amount forming the protein corona depends on the serum type used and the serum concentration. On PLGA NPs incubated with either FBS or human serum a clear difference in qualitative corona protein composition was identified by SDS-PAGE and LC-MS/MS in combination with bioinformatic protein classification. In the case of human serum a considerable change in corona composition was observed leading to a concentration-dependent desorption of abundant proteins in conjunction with an adsorption of high-affinity proteins with lower abundance. Cell incubation experiments revealed that the respective corona composition showed significant influence on the resulting nanoparticle-cell interaction. Conclusion: Controlling protein corona formation is still a challenging task and our data highlight the need for a rational future experimental design in order to enable a prediction of the corona formation on nanoparticle surfaces and, therefore, the resulting biodistribution in the body.

Project description:The potential applications of nanomaterials as drug delivery systems and in other products continue to expand. Upon introduction into physiological environments and driven by energetics, nanomaterials readily associate proteins forming a protein corona (PC) on their surface. This PC influences the nanomaterial's surface characteristics and may impact their interaction with cells. To determine the biological impact of nanomaterial exposure as well as nanotherapeutic applications, it is necessary to understand PC formation. Utilizing a label-free mass spectrometry-based proteomics approach, we examined the composition of the PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum, washed, coronal proteins solubilized, and proteins identified and quantified by label-free LC-MS/MS. To determine which attributes influence PC formation, the AgNPs were characterized in both water and cell culture media with 10% FBS. All AgNPs associated a common subset of 11 proteins including albumin, apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP-stabilized AgNPs were found to bind the greatest number of proteins (79 and 85 respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48 respectively), suggesting a difference in PC formation based on surface curvature. While no relationships were found for other protein parameters (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate) consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that this class of proteins are more receptive to curvature-induced folding and crowding in exchange for an increased hydration in the aqueous environment. These observations demonstrate the significance of electrostatic and hydrophobic interactions in the formation of the PC which may have broad biological and toxicological implications.

Dataset Information

Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS.

Publications

Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS.

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