美利体育登录入口官网:通过解码复杂微环境实现的精准光疗
Precision Phototherapy Enabled by Decoding Complex Microenvironments
作者:Qihang Ding;Manlin Qi;Wen Li;Meiqi Li;Jiling Xu;Yujin Kim;Goeun Kim;Biao Dong;Lin Wang;Jong Seung Kim;
DOI:https://doi.org/10.1021/acs.accounts.5c00488
引用量:80
发表时间:2025年
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美利体育登录入口官网:摘要
点击复制章节链接章节链接已复制!高分辨率图像下载MS PowerPoint幻灯片概要病理部位复杂且动态的微环境,包括感染、肿瘤和神经系统疾。捎谔晃陕、局部酸性、生物膜屏障和热适应等特征,对传统疗法提出了严峻挑战。利用这些微环境线索设计光激活、响应微环境的治疗平台,为实现精准、时空可控的治疗提供了有前景的策略。 营养免疫通过限制铁的可用性来抑制病原体增殖,而细菌则利用专门的铁载体介导的摄取系统来规避这种限制。通过利用这种脆弱性,“特洛伊木马”纳米平台(如多功能纳米复合材料Ga-CT@P)可以劫持细菌的铁摄取途径,诱导铁饥饿,并发挥强大的抗菌作用。密度泛函理论(DFT)计算揭示了Ga?+与肠杆菌素的结合强度和均匀性均优于Fe?+,从而形成稳定且不易还原的复合物,误导细菌的运输系统。 除了金属离子干扰外,酸响应性光动力疗法(PDT)在感染部位提供时空精确的激活,同时最大限度地减少脱靶毒性。我们开发了DHTPA,一种pH响应的AIE光敏剂,可在轻度酸性条件下专一性地生成大量活性氧(ROS),增强杀菌效果。该平台对耐药病原体表现出强抗菌作用,并在体内有效促进伤口愈合,展示了病变部位特异性“按需”PDT的潜力。 为克服生物膜屏障,OMV伪装的纳米伪装剂协同整合光热加热、离子干扰和ROS生成,以分解生物膜并诱导病原体代谢崩溃。同时,OMV包覆的纳米伪装剂利用细菌的黏附途径实现靶向递送,从而实现病原体代谢的光子破坏。 在热敏感微环境中,由于热休克蛋白介导的热耐受性限制了光热疗法(PTT),我们开发了使用NIR-II AIEgens(PM331@F127)的双激光PTT策略,以实现精确的分步热调节。该策略在较高温度下快速抑制热耐受机制,同时保持适度的热消融,在最大化疗效的同时减少继发性损伤。 在高屏障系统如中枢神经系统(CNS)中,穿越血脑屏障(BBB)对于有效光疗至关重要。我们设计了DK@RA-PEG,一种功能化RVG肽和核酸适配体的NIR-II光敏剂平台,以实现BBB穿透、病毒特异性靶向,并在NIR光照射下通过ROS介导的病毒清除。该方法在体内有效治疗狂犬病毒的同时,维持了……
美利体育登录入口官网:Abstract
AbstractClick to copy section linkSection link copied!High Resolution ImageDownload MS PowerPoint SlideConspectusThe complex and dynamic microenvironments of pathological sites, including infections, tumors, and neurological disorders, impose formidable challenges on conventional therapies due to features such as iron dysregulation, localized acidity, biofilm barriers, and thermal adaptation. Harnessing these microenvironmental cues to design light-activated, microenvironment-responsive therapeutic platforms offers a promising strategy for precise, spatiotemporally controlled treatments.Nutritional immunity restricts iron availability to suppress pathogen proliferation, while bacteria deploy specialized siderophore-mediated uptake systems to circumvent this restriction. By exploiting this vulnerability, “Trojan horse” nanoplatforms such as a multifunctional nanocomposite (Ga-CT@P) can hijack bacterial iron uptake pathways, induce iron starvation, and exert potent antimicrobial effects. DFT calculations revealed that Ga3+ exhibits stronger, more uniform binding to enterobactin than Fe3+, leading to stable, redox-inert complexes that mislead bacterial transport systems.Beyond metal ion interference, acid-responsive photodynamic therapy (PDT) offers spatiotemporally precise activation at infectious sites while minimizing off-target toxicity. Our development of DHTPA, a pH-responsive AIE photosensitizer, enables robust reactive oxygen species (ROS) generation exclusively under mildly acidic conditions, enhancing bactericidal efficacy. This platform demonstrated strong antibacterial effects against drug-resistant pathogens and effectively promoted wound healing in vivo, showcasing the potential of lesion-specific “on-demand” PDT.To address biofilm barriers, OMV-camouflaged nanodisguisers synergistically integrate photothermal heating, ion interference, and ROS generation to dismantle biofilms while inducing metabolic collapse in pathogens. Simultaneously, OMV-coated nanodisguisers exploit bacterial adhesion pathways for targeted delivery, enabling photonic disruption of pathogen metabolism.In thermosensitive microenvironments, where heat-shock-protein-mediated thermal tolerance limits photothermal therapy (PTT), we developed dual-laser PTT strategies using NIR-II AIEgens (PM331@F127) to achieve precise, stepwise thermal regulation. This strategy rapidly suppresses heat tolerance mechanisms at higher temperatures and maintains moderate thermal ablation, maximizing efficacy while reducing collateral damage.In high-barrier systems such as the central nervous system (CNS), crossing the blood–brain barrier (BBB) is essential for effective phototherapy. We designed DK@RA-PEG, an NIR-II photosensitizer platform functionalized with RVG peptides and nucleic acid aptamers, to enable BBB penetration, virus-specific targeting, and ROS-mediated viral eradication under NIR light. This approach demonstrated effective treatment of rabies virus infection in vivo while maintaining neurocompatibility.Collectively, these advances establish a versatile framework for microenvironment-responsive, light-controlled therapies that decode and harness biochemical and physical signatures within diseased tissues, achieving spatiotemporal precision beyond conventional modalities. By integrating chemical signaling modulation, smart molecular design, and physiological barrier penetration, these platforms illuminate a path toward intelligent, personalized phototherapies for complex disease landscapes.This publication is licensed for personal use by The American Chemical Society. ACS PublicationsCopyright ? 2025 American Chemical SocietySubjectswhat are subjects Article subjects are automatically applied from the ACS Subject Taxonomy and describe the scientific concepts and themes of the article. Biofilms Cancer therapy Infectious diseases Iron Tumors
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