| In recent years,cancer has become the leading cause of death worldwide.Therefore,researchers are devoted to developing effective anticancer strategies and treatments.Chemotherapy is one of the main methods for the treatment of cancer at present,but chemotherapy has no specific selectivity for tumor cells,it also seriously affects the function of normal cells while fighting cancer,causing serious adverse reactions such as gastrointestinal discomfort and hair loss.The rapid development of materials can effectively solve this problem.Peptide nanomaterials have good biocompatibility and low toxicity.Through the enhanced penetration and retention(EPR)effect,the enrichment of anticancer drugs in tumor sites can be significantly improved,and the side effects of traditional treatment methods can be reduced as much as possible.However,due to non-covalent bond binding,peptide nanomaterials are unstable,easily degraded in vivo,and have a short residence time at tumor sites,making it difficult to achieve in situ self-assembly of peptide nanomaterials in vivo.Mitochondria are the supplier of cell energy,the controller of tumor cell apoptosis,and maintain the environment of cell redox balance.The peptide nanomaterial targeting mitochondria was developed to make it responsively assembled at the mitochondrial site.Altering mitochondrial membrane potential,increasing mitochondrial membrane permeability,causing mitochondrial damage and inducing tumor cell apoptosis is a promising therapeutic strategy.In this paper,a ROS-responsive peptide nanomaterial was synthesized,which can be assembled in solution to form nanoparticles,enter tumor cells through endocytosis and target mitochondria,and mitochondria generate more reactive oxygen species(ROS),nanoparticles form nanofiber dimers through the coupling of disulfide bonds through thiol oxidation.Subsequently,an ordered structure is formed between the dimers through hydrogen bonding,which shortens the distance between the dimers,thereby forming an ordered fiber network.The strategy of cross-linking-induced assembly by covalent bonding on intracellular subcellular organelles enhances the synergistic effect of multivalent bonds with mitochondria,making it more interacting sites with mitochondria and stronger binding force with mitochondria,thereby improving the stability of peptide nanomaterials.Using exogenous ultrasound(US)to activate the sonosensitizer to generate singlet oxygen,induce mitochondrial apoptosis,and thus have an anti-tumor effect.First,ROS-responsive peptide nanomaterials P1 and P2 were synthesized by solid-phase synthesis,the critical micelle concentration(CMC)of the materials was determined,and their ROS responsiveness and assembly properties were explored.Secondly,the targeting performance and induced membrane potential changes of peptide nanomaterials in mitochondria were explored by laser confocal microscopy at the cellular level.Finally,in vivo experiments were carried out to explore the targeting of peptide nanomaterials at the tumor site in vivo and the inhibition of tumors.The experimental results showed that ROS-responsive peptide nanomaterials have good anti-tumor ability.In summary,based on the concept of in vivo self-assembly,this project designed and synthesized ROS-responsive peptide nanomaterials,which fully combined the characteristics of tumor cell mitochondria to realize the regulation of the in situ morphology of peptide self-assembled nanomaterials in mitochondria,forming a twodimensional shape.Peptide nanofiber network can combine with mitochondria,use mitochondrial endogenous ROS to trigger the coupling of peptide nanomaterials covalent bonds,enhance the synergy of multivalent bonds,improve the stability of polypeptides,and further induce by exogenous US apoptosis of cells.This strategy provides a new way for nanomedicine in tumor therapy. |
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