Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY / 药物分析学报

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Formation and characteristics of polystyrene nanoplastic-plant protein corona / 生物工程学报

To investigate the formation of polystyrene nanoplastic-plant protein corona and its potential impact on plants, three differently modified polystyrene nanoplastics with an average particle size of 200 nm were taken to interact with the leaf proteins of Impatiens hawkeri for 2 h, 4 h, 8 h, 16 h, 24 h, and 36 h, respectively. The morphological changes were observed by scanning electron microscopy (SEM), the surface roughness was determined by atomic force microscopy (AFM), the hydrated particle size and zeta potential were determined by nanoparticle size and zeta potential analyzer, and the protein composition of the protein corona was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteins were classified in terms of biological processes, cellular components, and molecular functions to study the adsorption selection of nanoplastics to proteins, investigate the formation and characteristics of polystyrene nanoplastic-plant protein corona and predict the potential impact of protein corona on plants. The results showed that the morphological changes of the nanoplastics became clearer as the reaction time extends, as evidenced by the increase in size and roughness and the enhancement of stability, thus demonstrating the formation of protein corona. In addition, the transformation rate from soft to hard protein corona was basically the same for the three polystyrene nanoplastics in the formation of protein corona with leaf proteins under the same protein concentration conditions. Moreover, in the reaction with leaf proteins, the selective adsorption of the three nanoplastics to proteins with different isoelectric points and molecular weights differed, and the particle size and stability of the final formed protein corona also differed. Since a large portion of the protein fraction in protein corona is involved in photosynthesis, it is hypothesized that the formation of the protein corona may affect photosynthesis in I. hawkeri.

Construction of albumin corona and its application in pharmaceutical preparation / 中国药科大学学报

@#Protein corona is a protein layer that adsorbs on the surface after nonspecific interactions between nanoparticles and plasma proteins.In recent years, studies have shown that modification of specific plasma proteins on the surface of nanoparticles to construct protein corona can prolong the blood half-life of nanoparticles and promote the targeted delivery of nanoparticles, which has attracted widespread attention to the study of drug-carrying systems, among which, albumin corona, the most abundant protein in blood, is the most widely studied.Based on the above, this paper systematically summarized the method of constructing albumin corona and its application in the research on pharmaceutical preparations, in order to provide reference for the construction of albumin corona in the process of drug preparation.

In vivo delivery process and regulating mechanisms of lipid-based nanomedicines / 药学学报

Lipid-based nanocarrier is a classic drug delivery system with great biocompatibility and biodegradability. It can effectively reduce the toxicity of anti-tumor and anti-infective drugs in clinical practice. However, it has not yet met the clinical demand for enhanced therapeutic efficacy, and the clinical application is still very limited. The complex in vivo delivery process of lipid-based nanomedicine and the reciprocal interactions with body lead to unexpected changes in in vivo performance of nanomedicine and seriously hinder clinical translation. Therefore, the in-depth study of the relationships among intrinsic properties of lipid-based nanomedicine, the in vivo delivery process, and the regulatory mechanisms will not only provide guidance for the rational design of nanocarriers, but also promote the clinical translation and precision medicine of new lipid-based nanomedicine. In this review, we summarize the in vivo delivery process, regulating factors and intervention strategies for the in vivo delivery of lipid-based nanomedicine.

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers / 药物分析学报

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Recommendations for specimen collection for detection and diagnosis of COVID-19 / Recomendações para a realização de coleta de amostras para detecção e diagnóstico de COVID-19

INTRODUCTION: The spread of SARS-CoV-2 has caused a global public health crisis (pandemic). One of the most important measures to control the transmission chain of the new coronavirus is to identify those infected through laboratory testing. OBJECTIVE: Synthesize the recommendations for the specimen collection for detection and diagnosis of COVID-19. METHODS: This is an integrative review, considering the publications of the following databases: PubMed and Google Academic from January 2020. RESULTS: 468 publications were identified, 20 of which were considered eligible. The publications recommend that technical training for specimen collection and careful observation of infection prevention protocols are fundamental. This manuscript highlights the steps for specimen collection as materials for collection, storage, transportation, individual protection, and laboratory analysis of samples. Currently, the Reverse Transcription - Polymerase Chain Reaction test is the recommended and gold standard method of identifying COVID-19 cases. Serological tests play an important role in research and surveillance. CONCLUSION: In summary, the documents ensure that the RT-PCR is the gold standard for SARS-CoV-2 detection and recommend standardization of collection and conditioning methods to avoid errors related to the collection and false negative results.

INTRODUÇÃO: A disseminação do SARS-CoV-2 ocasionou uma crise na saúde pública mundial (pandemia). Uma das mais importantes medidas de controle da cadeia de transmissão do novo coronavírus consiste em identificar os infectados por meio de teste laboratorial. OBJETIVO: Sintetizar as recomendações para a coleta de amostras para detecção e diagnóstico da COVID-19. MÉTODO: Trata-se de uma revisão integrativa, considerando as publicações do Google Acadêmico e Pubmed a partir de janeiro de 2020. RESULTADOS: Foram identificadas 468 publicações, das quais 20 foram consideradas elegíveis. As publicações recomendam que a capacitação técnica para a coleta das amostras e a observação criteriosa de protocolos de prevenção de infecção são fundamentais. Destacam-se nesse artigo as etapas para a coleta de amostras como materiais para coleta, armazenamento, transporte, proteção individual e análise laboratorial das amostras. Atualmente, o teste de Reverse Transcription - Polymerase Chain Reaction é o método recomendado e padrão-ouro para a identificação dos casos de COVID-19. Os testes sorológicos desempenham um papel importante na pesquisa e vigilância. CONCLUSÃO: Em síntese, os documentos asseguram que o RT-PCR é o teste padrão-ouro para detecção do SARS-CoV-2 e recomenda a padronização dos métodos de coleta e acondicionamento, a fim de evitar erros relacionados com a coleta e resultados falso-negativos.

Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study

When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to

Preparation and targeting capability of corona forming in human ovarian plasma / 药学学报

After entering the physiological environment, proteins and other biomolecules bind to the nanoparticles' surface, called protein corona. The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors. Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona. With folic acid (FA)-modified polylactic acid-polyglycolic acid copolymer (PLGA) nanoparticles, the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma. All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee (2019-409-1). Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed. The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct, particularly for proteins with molecular weight of 45, 110 and >180 kDa. Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells. Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization. The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions. Additionally, the protein corona in different diseases is emerging as a key point; thus, a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.

Research advances in the effect and utilization of protein corona on the circulation of nanoparticles in vivo / 药学学报

Nanoparticles have better applicability in the detection, treatment of cancer and various difficult diseases, but mononuclear phagocytosis system can seriously shorten the time of nanoparticles in vivo circulation, reduce the drug efficacy. The protein crown formed on the surface of the nanoparticle after entering the body can change its surface properties, interfere with the recognition of phagocytes, and thus affect its circulation time in vivo. This article outlines the general composition and formation process of protein crowns. It also summarizes the influence of the physical and chemical properties of nanoparticles, such as particle size, surface charge, hydrophilicity and surface materials on the formation of protein crowns. The protein crown affects the circulation of nanoparticles in vivo, mainly because the adsorbed opsonic protein promotes cell phagocytosis. Therefore, we also introduce the method of using protein crowns to promote the long circulation of nanoparticles in vivo. By designing appropriate physical and chemical properties, surface modification, and directed design of protein crowns, the adsorption of proteins on the surface of nanoparticles can be reduced. Therefore, it can reduce the clearance of nanoparticles in the mononuclear phagocytic system (mainly the phagocytes of the liver and spleen), and achieve the goal of long circulation of nanoparticles in the body.

Plasma proteins regulating in vivo performance of liposomes / 药学学报

Liposomes have been widely exploited in clinics. After entry into blood stream, liposomes absorb a large number of plasma proteins to form protein corona, which severely regulates in vivo performance of liposomes. It is of high importance to study the relationships among liposome surface properties, plasma protein components and liposome in vivo performance for clinical translation. In this review, we will summarize the factors affecting liposome protein corona, the effects of protein corona on liposome performance and the rational design of liposomes, aiming to accelerate clinical translation of liposome-based therapeutics.