基于多肽和蛋白质分子的纳米生物界面效应及其应用研究

Peptide-/protein-mediated nano-bio interface and its applications

通过对纳米结构进行表面生物和化学修饰,能够赋予其崭新的界面性质.本文概述了纳米颗粒表面共价修饰和非共价修饰多肽和蛋白质的常用方法,对比了两种修饰方法的优缺点以及构筑纳米生物结构存在的问题;并介绍了多肽和蛋白质界面修饰在改善纳米颗粒生物稳定性、生物分布和靶向性方面的研究工作;在此基础上介绍了纳米生物结构基于抗原-抗体特异性识别在生物检测领域的应用;此外,简单介绍了纳米生物结构在应用过程中所面临的挑战.希望本综述能够有助于科技工作者了解纳米生物结构的构筑方法及其应用方面的进展和挑战,为多肽和蛋白质修饰纳米结构的设计合成提供一些启发和思路.

Surface modification can impart nanostructures new interface properties.In this review,we summarize the representative surface modification methods of nanoparticles with peptides and proteins.The biomolecules can be conjugated with nanoparticles by noncovalent and covalent coupling.Both of these approaches have strengths and limitations.Physical adsorption is the most direct and simplest noncovalent method but peptides and proteins adsorbed on solid surface always loss their native structures and biological activity and the behavior of peptides and proteins on surface is still difficult to regulate precisely.A popular noncovalent conjugation with stability and selectivity is via biotin-streptavidin interaction.Covalent attachment is more stable and selective than noncovalent methods.The stability of covalent biomolecule-nanostructure conjugates makes this strategy useful for applications in biological media with other interfering species.1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC)/N-hydroxysuccinimide(NHS) strategy is widely used for covalent bioconjugation with well-established protocol,but it could lead to hydrolysis problem,crosslinking and uncontrolled heterogeneous orientation.The click chemistry is another covalent strategy with higher selectivity and yield,while it takes an extended reaction time.In addition to considering stability,selectivity,reaction time,and yield mentioned above,covalent bioconjugation should proceed in mild condition and the reagents required should have no interference on properties of biomolecules and nanostructures.In recent years substantial progress has been made in the formation of bionanoconjugates,but there is still no completely reliable approach for biomolecule-nanosturcture conjugation.Heretofore fine-tuning the structure and orientation of peptides and proteins on surface has been challenging.The efforts on improving biostability,biodistribution and targeting of nanoparticles with peptides and proteins functionalization are introduced.Nanostructures are often used within body in biomedical applications,so they must overcome an ensemble of biological obstacles to perform their function.First they may suffer from clearance from the body’s immune system.Even though they can escape from clearance,they are required to arrive their correct battlefield.What’s more,nanostructures need to cross cell membrane barriers and reach specific organelles such as nucleus and mitochondria to function in most cases.Peptide-and protein-nanostructure conjugation has been emerged as a useful tool to address these problems mentioned above.They could provide nanostrctures protection from phagocytic clearance and promote persistent circulation.Nanostructures can penetrate cell membrane easily with cell-penetrating peptide modification.The specific recognition of biological molecules imparts nanostructures targeting ability.In addition,the applications in fields such as diagnostics are introduced based on antigen-antibody specific recognition.The problems that bionanoconjugates for medical applications may encounter in use are presented briefly.Once contacting with biological matrices,nanostructures will be immediately coated by proteins,forming a protein corona.This protein layer could make significant changes in nanostructure properties such as size,surface charge and even the bioactivity of the peptides and proteins conjugated on its surface,which provides nanostructure with a new biological identity.Some previous results suggested that protein-functionalized nanoparticles lost their targeting capabilities when a protein corona adsorbed on the surface.In short,not only should bioconjugation methods be picked carefully depending on the goals,but also the effects of the complex use environment on bionanoconjugates should be taken into consideration.This review is intended to help researchers get an idea of the progress and dilemma of bionanoconjugate construction and its applications,and provide some inspiration for design and synthesis of peptide and protein-modified nanostructures.