Assembly Of Collagen-Aunps Towards Biomedical Application

The combination of natural protein-collagen and inorganic nanometer particles(NPs)-AuNPs,can solve the disadvantages of both collagen and AuNPs efficiently.As the collagen usually have poor mechanical properties and rapid degradation performance,and the AuNPs show poor biocompatibility.The hybrid collagen-AuNPs will combine the merits of biological properties of collagen and physics characteristics of AuNPs,meanwhile,exhibits new outstanding properties.Although,the benefits of hybrid collagen-AuNPs materials are obvious,the toxicity and bioincompatibility of the products remaining on the surface of AuNPs caused by chemical reduction reaction are potentially harmful for futher applications in biomedical,should not be ignored.Based on these above,we presente a one-step biomimetic synthesis of collagen-AuNPs core-shell nanoconjugates or collagen-AuNPs based hydrogel,without use of any reducing and stabilizing agents,in a facile,but environmentally friendly and effective manner.It is proved that the collagen-AuNPs composite materials have enhanced mechanical properties and rheological performances,good biocompatibility,high security.And achive good results in the application on promoting cell adhesion,growth,and differentiation;regulating cell growth and apoptosis;localized reservation and sustained release of therapeutic drugs and anti-tumor therapy.First,based on the mechanism of biomineralization reaction,we have presente a one-step synthesis of colloidal gold-collagen core-shell nanoconjugates with good biocompatibility,high safety and a relatively narrow distribution of 50 ± 20 nm.Core-shell AuNPs coating with collagen show high stability and good dispersion in water.The formation of AuNPs has a negligible influence on the secondary structures of collagen protein,indicating the biocompatibility of the reaction.This approach can be extended for synthesis of other noble metal nanoparticles such as AgNPs and Pt NPs,indicating the general suitability.Then,we explore its formation mechanism through both experimental tests and computer simulation.Electrostatic complexation of negatively charged gold ions with positively charged collagen chains plays important role in the whole reaction.As reducing by hydroxyproline residues of collagen,collagen alone serves as either a reducing agent or a stabilizer for the formation of gold nanoparticles.Second,based on the electrostatic interaction,we prepare collagen-Au NPs composite film with the assistance of the layer-by-layer assembly method,which shows enhanced mechanical properties and excellent biocompatibility and promotes 3T3 fibroblast cell growth and differentiation.What's more,it is efficient and flexible for regulating cell growth and death after loading the photosensitizer drug into the hybrid multilayer film mentioned above.The photosensitizer drugs can be activated with laser illumination of a certain wavelength yielding ROS,responsible for triggering cell death.Whereas other cells,in contact with the flm but not illuminated by the laser,remain original state,indicating the safety of this method and the biocompatibility of the hybrid materials.Besides,based on the electrostatic interaction between positively charged collagen chains and anionic clusters([AuCl4]-ions),we present a gold-biomineralization-triggered self-assembly method and synthesize injectable and self-healing collagen-protein-based hydrogel.The locally synthesized gold nanoparticles are demonstrated to tune the mechanical properties of the collagen-based hydrogels,in which reversible weak interactions between collagen chains and gold nanoparticles endow the hydrogels with shear-thinning and self-healing functions.This kind of injectable hydrogel can be used for anti-tumor therapy,especially for the treatment of superficial tumors.Such collagen-based composites hydrogels use as a novel tool for localized reservation and sustained release of therapeutic drugs,with the advantages to reduce the drug dosage,to lower the toxicity,and to improve the bioavailability.Then we evaluate the anti-tumor effects including photothermal therapy and combinatorial therapy.The results show that the growth of tumor significantly inhibited but the mice remained healthy.We also propose the strategy as “one injection,multiple treatments”,and achieve enhanced anti-tumor effect.