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

Abstract

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 bodys immune system. Even though they can escape from clearance, they are required to arrive their correct battlefield. Whats 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.