Construction Of The Targeted Nano-delivery System And Its Application In Biomedicine

Delivering therapeutic agents to specific diseased tissues or cells with minimal toxic side effects is critical for diagnosing and treating patients.Nanomaterials are widely used as diagnostic tools or to deliver therapeutic agents to specific sites in a controlled manner due to their uniform pore structure,easy modification,and unique catalytic activity.Over the past few decades,researchers have enriched and developed methods for the synthesis and characterization of nanoparticles,and demonstrated their utility in targeting,imaging and treating diseases.Based on the targeted nano-delivery system,a series of neutrophil membranetargeted multifunctional nanoplatforms have been constructed and used for the treatment of inflammation-related diseases.In addition,we also construct an actively targeted nanomotor catalyst for the synthesis of deep bioorthogonal antibacterial drugs for the treatment of infections.The main results are summarized as follows:1.Carbon monoxide(CO)plays a key role in the regulation of various physiological processes and is therefore considered as a promising agent.However,therapeutic applications of CO are severely hampered by the difficulty of the delivery of controlled amounts of CO to biological targets.To solve this issue,we develop a spatiotemporally controllable CO-releasing platform(designated as NeuMnO2/Fla)for synergistic anti-inflammation.Neu-MnO2/Fla can target to inflammatory sites with the help of neutrophil membranes.Then,excess H2O2 at the inflamed tissues can be decomposed into oxygen because of MnO2 as nanozymes possessing catalase(CAT)activity,which not only relieves oxidative stress but also enables in situ rapid photo-induced CO release.The in vitro and in vivo results demonstrate the CO-releasing platform has a strong synergistic anti-inflammatory effect.2.Alzheimer’s disease(AD)is one of the most fatal and irreversible neurodegenerative diseases.Despite the progress made with recent clinical use of inhibitors of acetylcholinesterase and amyloid-β(Aβ)antibodies,the curative effects of AD treatment remain unsatisfactory,which is probably due to the complexity of pathogenesis and the multiplicity of therapeutic targets.Here,a neutrophil membrane-coated MOF nanozyme(denoted as Neu-MOF/Fla)is developed to destroy the malignant Aβ deposition-inflammation cycle and ameliorate the pathological network for effective AD treatment.The Neu-MOF/Fla could recognize the pathological inflammatory signals of AD,and deliver the photo-triggered antiinflammatory CO and MOF-based hydrolytic nanozymes to the lesion area of brain in a spontaneous manner.Based on our investigations in vitro and in vivo,NeuMOF/Fla significantly suppresses the neuroinflammation,mitigates the Aβ burden,beneficially modulates the pro-inflammatory microglial phenotypes and improves the cognitive defects.Our work will offer new opportunities to explore biomimetic multifunctional nanotherapeutics for the treatment of AD and even many other multiple symptoms-associated neurodegenerative diseases.3.Cu(Ⅰ)-catalyzed azide-alkyne cycloaddition(CuAAC)reaction has been widely regarded as a promising avenue in bioorthogonal chemistry.The emerging heterogeneous copper catalysts have been developed with a series of exciting applications in situ activation of prodrugs because of their excellent stability and biocompatibility.However,due largely to the complex biophysical barriers in living organisms,most synthetic bioorthogonal drugs cannot penetrate deep pathological tissues.Especially in biofilm-associated infections,the biofilms severely block the penetration of traditional antimicrobial agents and increase the antibiotic resistance,which makes it extremely difficult to eliminate the biofilms.Inspired by selfpropelled biological motors,such as enzymes,herein we develop a NIR light controllable carbonaceous nanocalabash(CNC)motor catalyst with good biocompatibility for active targeted synthesis of drugs inside the biofilms,as a robust general-purpose bioorthogonal platform.Under the NIR laser,the CNC motor catalysts display a rapid autonomous motion and generate active molecules in the deep biofilm layers,removing the biofilms and eradicating the shielded bacteria.Our work will shed light on developing robust bioorthogonal platform for active targeted synthesis of drugs in deep-layered living systems.