摘要
近年来,刺激响应性肽纳米材料(stimuli-responsive peptide nanomaterials,SRPNs)因其出色的功能性和环境响应特性,成为纳米生物材料领域的重要研究方向.SRPNs能够感知病理微环境中的特定刺激,通过精准调控自组装或解组装,为生物医学应用提供创新解决方案.通过分子设计,SRPNs不仅具有特异性响应能力,还兼具优异的生物相容性,显著提升了治疗效率并降低了副作用.本综述对SRPNs的设计策略及其在生物医学领域的应用进行了全面梳理,着重阐述了SRPNs对pH、氧化还原、酶和温度等刺激的响应机制和SRPNs在药物递送、生物成像、抗菌及伤口愈合等方面的应用.最后,讨论了SRPNs在实际应用中面临的生物相容性、稳定性及体内精确刺激响应等挑战,并对其未来发展进行了展望.期望本文能为相关领域的深入研究提供方向,助力SRPNs的创新发展.
Stimuli-responsive peptide-based nanomaterials(SRPNs)have emerged as a revolutionary class of smart biomaterials,transforming biomedical applications through their inherent structural adaptability,intrinsic biocompatibility,and precise microenvironmental sensitivity.By capitalizing on the programmable self-assembly characteristics and natural biocompatibility of peptides,SRPNs enable spatiotemporally precise control over therapeutic delivery,bioimaging,and tissue regeneration.This comprehensive review delineates recent advances in SRPN design strategies,biomedical implementations,and translational challenges.pH-responsive systems utilize protonation-sensitive motifs(e.g.,histidine imidazole groups,aspartic acid carboxyls)or acid-labile linkages(Schiff bases,hydrazones)to trigger payload release or antimicrobial activation in the acidic microenvironments found within tumors and biofilms.Notable examples include histidine-rich 3IH3 antimicrobial peptides that adoptα-helical membrane-disrupting conformations under acidic conditions,and C16-VVAEEE nanofibers forming tumor-localized hydrogels for extended drug retention.Redox-responsive platforms exploit sulfur/selenium-based moieties(thioethers,disulfides)undergoing ROS or GSH-mediated transformations for oxidativeenvironment triggered destabilization,exemplified by mPEG-b-PDTG micelles releasing chemotherapeutics through ROS-induced sulfoxide conversion.Alternatively,the in vitro stability can be increased through disulfide bonds to avoid premature self-assembly.In the environment with a high concentration of glutathione(GSH)in tumor cells,the disulfide bonds are reduced and broken,and then selfassemble into nanofibers through hydrophobic interactions.In this way,tumor-specific activation and targeted therapy can be achieved while avoiding systemic toxicity.Enzyme-activated SRPNs integrate protease-specific cleavage domains(MMP-2,cathepsin B)for targeted payload delivery,demonstrated by tumor microenvironment-responsive WINNER nanocapsules exposing therapeutic proteins through protective shell shedding,and lysosome-sensitive RH-(GFLG)3 nanoparticles for doxorubicin release.Thermoresponsive architectures employing phase-transitioning peptides(elastin-like polypeptides)exploit LCST/UCST properties to create injectable depots for sustained therapy,such as endothelial cell-encapsulating CUBES hydrogels and temperature-threshold reconfigurable EBPRBP copolymers.Multi-stimuli systems enhance precision through synergistic triggers:pH/enzyme-responsive nanocarriers enable sequential PEG deshielding and MMP-sensitive linker degradation for enhanced tumor penetration,while ROS/temperature dualresponsive hydrogels combine oxidative dissolution with thermogelation for localized chemoimmunotherapy.In biomedical applications,SRPNs demonstrate remarkable versatility.Drug delivery platforms achieve tumor-specific accumulation through size-switchable nanoparticles or charge-reversal micelles,significantly enhancing therapeutic indices compared to conventional therapies while minimizing systemic toxicity.Bioimaging innovations employ enzyme-activated probes(TER-SA)maintaining near-infrared fluorescence in tumors,or acid-triggered peptide-porphyrin conjugates switching between diagnostic nanoparticles and therapeutic nanofibers.Antimicrobial SRPNs utilize infection-associated acidity to activate membranolytic peptides(3IH3,F5)or enzymatically cleavable polyelectrolytes(PTPMN),effectively eradicating resistant biofilms with minimized off-target effects.Chronic wound repair benefits from ROS-scavenging hydrogels mitigating inflammation,MMP-responsive matrices promoting angiogenesis,and thermosensitive depots releasing growth factors to accelerate collagen remodeling,achieving over 90%wound closure rates in diabetic models.Despite these advances,SRPN translation faces challenges including the limited functional diversity of natural amino acid building blocks,unpredictable biological interactions in complex systems,and difficulty in balancing stimulus responsiveness with material stability.Future development requires the integration of non-canonical amino acids,machine learning-guided peptide design,and biomimetic dynamic networks for programmable multistimuli systems.Progress in scalable manufacturing,immunocompatibility optimization,and real-time biodistribution monitoring will bridge the gap between laboratory innovation and clinical implementation.Through the convergence of peptide engineering,systems biology,and precision medicine,SRPNs promise to revolutionize therapeutic paradigms in oncology,antimicrobial resistance,and regenerative medicine,ultimately enabling personalized interventions tailored to pathological microenvironments.
作者
苏运哲
吕银凤
冯兴军
毕重朋
单安山
Yunzhe Su;Yinfeng Lv;Xingjun Feng;Chongpeng Bi;Anshan Shan(College of Animal Science and Technology,Northeast Agricultural University,Harbin 150030,China)
出处
《科学通报》
北大核心
2025年第22期3764-3778,共15页
Chinese Science Bulletin
基金
黑龙江省重点研发计划(2024ZXDXB58)
国家重点研发计划(2023YFD1301104)资助。
关键词
刺激响应性肽纳米材料
自组装
微环境响应
精准治疗
stimuli-responsive peptide nanomaterials
self-assembly
microenvironment response
precision therapy
