Biocompatibility of mannan nanogel鈥攕afe interaction with plasma proteins

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• 作者：Sí ; lvia A. Ferreira^a ; ^{silviarmferreira@gmail.com} ; Cecilia Oslakovic^b ; ^{cecilia.oslakovic@gmail.com} ; Risto Cukalevski^c ; ^{risto.cukalevski@biochemistry.lu.se} ; Birgitta Frohm^c ; ^{birgitta.frohm@biochemistry.lu.se} ; Bjö ; rn Dahlbä ; ck^b ; ^{bjorn.dahlback@med.lu.se} ; Sara Linse^c ; ^{sara.linse@gmail.com} ; Francisco M. Gama^a ; ^{fmgama@deb.uminho.pt} ; Tommy Cedervall^c ; ^{tcedervall@yahoo.com}
• 关键词：Mannan nanogel ; Protein corona ; Coagulation ; Fibrillation ; Biosafety ; Biocompatibility
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2012
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：July, 2012
• 卷：1820
• 期：7
• 页码：1043-1051
• 文件大小：704 K

摘要

Background

Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents.

Methods

Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid 尾 peptide and hemodialysis-associated amyloidosis 尾2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively.

Results

The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation.

Conclusions

Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications.

General Significance

Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science.