Advanced drug delivery reviews最新文献_第4页

Polymer-based nanomedicines: Supporting multimodal approaches to glioblastoma multiforme treatment 聚合物基纳米药物：支持胶质母细胞瘤多模式治疗

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-19 DOI: 10.1016/j.addr.2025.115735

Amina Benaicha-Fernández , Stuart P. Atkinson , Inmaculada Conejos-Sánchez , Maria Medel , María J. Vicent

Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal cancers affecting the central nervous system (CNS), with significant obstacles precluding effective diagnosis, treatment, and monitoring including the presence of the blood-brain barrier, tumor heterogeneity, and an immunosuppressive tumor microenvironment. Polymer-based nanomedicines have emerged as a promising approach to overcome these barriers, offering innovative targeted diagnostic and therapeutic strategies for GBM patients. This review provides an overview of why GBM remains a diagnostic and therapeutic challenge and provides a summary of recent high-impact studies that explored how polymers and polypeptides can be employed to promote blood-brain barrier penetration and tumor accumulation and provide positive therapeutic outcomes. We also discuss the use of polymers/polypeptides in the development of multimodal therapies for GBM, including the combination of chemotherapeutic and molecularly targeted drugs/treatments, explore how they support the combination of distinct therapeutic modalities (such as phototherapy and immunotherapy) in a single platform, and describe how they apply to the development of novel GBM theranostic strategies. We then discuss the preclinical validation of polymer-based therapeutic approaches to GBM by exploring recent advances in complex in vitro and in vivo models. Finally, we look to the future of GBM treatment with nanomedicines, describing emerging therapeutic strategies for GBM and how we may boost the clinical translation of often complex polymer-based nanomedicines. Overall, this review provides robust evidence for the relevance of polymer-based nanomedicines in GBM treatment.

多型胶质母细胞瘤（GBM）仍然是影响中枢神经系统（CNS）的最具侵袭性和致死性的癌症之一，存在着阻碍有效诊断、治疗和监测的重大障碍，包括血脑屏障、肿瘤异质性和免疫抑制肿瘤微环境的存在。聚合物基纳米药物已经成为克服这些障碍的一种有希望的方法，为GBM患者提供了创新的靶向诊断和治疗策略。这篇综述现在概述了为什么GBM仍然代表着诊断和治疗的挑战，然后总结了最近一些高影响力的研究，这些研究探讨了聚合物和多肽如何促进血脑屏障渗透、肿瘤积累和积极的治疗结果。此外，我们讨论了聚合物/多肽在GBM多模式治疗开发中的应用，包括化疗和分子靶向药物/治疗的结合，探讨了它们如何支持不同治疗方式的结合，如光疗和免疫疗法，在一个平台上，并描述了它们如何应用于新型GBM治疗策略的开发。我们还通过探索复杂体外和体内模型的最新进展，讨论了基于聚合物的GBM治疗方法的临床前验证。最后，我们展望了纳米药物治疗GBM的未来，在那里我们描述了GBM的新兴治疗策略，以及我们如何促进通常复杂的聚合物基纳米药物的临床转化。总的来说，我们认为这篇综述为聚合物基纳米药物与GBM治疗的相关性提供了强有力的证据。

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引用次数: 0

Spatial patterning strategies for liver tissue engineering: Biofabrication technologies and applications 肝组织工程的空间模式策略：生物制造技术和应用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-15 DOI: 10.1016/j.addr.2025.115737

Haram Nah , Ashlin R. Michell , Kerry M. Rogy, Owen J. Lally, Salman R. Khetani

The liver is composed of hepatocytes and non-parenchymal cells arranged in precise spatial patterns that enable more than 500 metabolic, synthetic, and detoxification functions. Replicating this hierarchical structure and dynamic multicellular organization is essential for applications in drug development and regenerative medicine. Here, we review biofabrication strategies that encode spatial control in engineered liver tissues. We begin with native hepatic architecture and cell sources, then evaluate self-assembled and engineered aggregates, soft lithography, electrospun scaffolds, three-dimensional bioprinting, and microfluidic systems in terms of their ability to capture physiological features such as zonation, polarity, and vascular or biliary networks. Hybrid approaches that integrate multiple modalities to enhance complexity and function are also highlighted. We next discuss how human liver models are advancing drug metabolism and toxicity screening, disease modeling, and potential therapeutic applications. Finally, we examine current limitations and future directions, emphasizing challenges of scalability, reproducibility, and standardization, along with emerging opportunities in volumetric bioprinting, machine learning–guided design, and regulatory qualification of liver microphysiological systems. Collectively, engineered liver models are poised to play an increasingly critical role in bridging in vitro and in vivo applications as advances in biofabrication bring them closer to clinical and regulatory translation.

肝脏由肝细胞和非实质细胞组成，它们以精确的空间模式排列，具有500多种代谢、合成和解毒功能。复制这种分层结构和动态多细胞组织对于药物开发和再生医学的应用至关重要。在这里，我们回顾了在工程肝组织中编码空间控制的生物制造策略。我们从天然肝脏结构和细胞来源开始，然后评估自组装和工程聚集体、软光刻、电纺丝支架、三维生物打印和微流体系统在捕捉生理特征（如分区、极性、血管或胆道网络）方面的能力。还强调了集成多种模式以增强复杂性和功能的混合方法。接下来，我们将讨论人类肝脏模型如何促进药物代谢和毒性筛选、疾病建模和潜在的治疗应用。最后，我们研究了当前的局限性和未来的方向，强调了可扩展性、可重复性和标准化方面的挑战，以及体积生物打印、机器学习指导设计和肝脏微生理系统监管资格方面的新机遇。总的来说，工程肝脏模型在体外和体内桥接应用中发挥着越来越重要的作用，因为生物制造的进步使它们更接近临床和调节翻译。

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引用次数: 0

Living materials for gas therapy 气体治疗用的生活材料

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-15 DOI: 10.1016/j.addr.2025.115738

Pei Pan , Tao Liu , Lu Zhang , Xian-Zheng Zhang

The clinical translation of gas therapy, which employs medical gases such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), hydrogen (H₂), and sulfur dioxide (SO₂), is mainly limited by the absence of delivery systems that can provide precise spatiotemporal control in complex pathological environments. While conventional nanocarriers have improved in gas delivery, they often suffer from limited biocompatibility, poor targeting, and insufficient responsiveness. Recently, living materials emerged as a promising and innovative paradigm. Engineered from biological entities such as bacteria, cells, and algae, or their biomimetic derivatives, these materials inherently exhibit bioactive functions, including disease tropism, immunomodulation, and dynamic responsiveness to microenvironmental cues, thereby enabling intelligent gas generation and controlled release. This review systematically summarizes recent advances in living material–based gas therapy, with emphasis on classification according to biological origin and engineering design principles. We further discuss their mechanisms, including genetic programming for autonomous gas production and hybrid architectures for stimuli-responsive release, and highlight their therapeutic efficacy in cancer, inflammatory diseases, and tissue regeneration. Finally, we outline the major challenges in biosafety and scalability, and provide forward-looking perspectives on the integration of synthetic biology and multimodal therapeutic strategies to advance the field of precision gas medicine.

使用医用气体如一氧化氮（NO）、一氧化碳（CO）、硫化氢（H2S）、氢气（H2）和二氧化硫（SO2）的气体疗法的临床转化主要受到缺乏能够在复杂病理环境中提供精确时空控制的输送系统的限制。虽然传统的纳米载体在气体输送方面有所改进，但它们往往存在生物相容性有限、靶向性差和响应性不足的问题。最近，生物材料作为一种有前途的创新范例出现了。这些材料由细菌、细胞和藻类等生物实体或其仿生衍生物改造而成，固有地表现出生物活性功能，包括疾病趋向性、免疫调节和对微环境线索的动态响应，从而实现智能气体产生和控制释放。本文系统地综述了基于生物材料的气体治疗的最新进展，重点介绍了基于生物起源和工程设计原则的分类。我们进一步讨论了它们的机制，包括自主产气的遗传编程和刺激反应释放的混合结构，并强调了它们在癌症、炎症性疾病和组织再生中的治疗功效。最后，我们概述了生物安全性和可扩展性方面的主要挑战，并就合成生物学和多模式治疗策略的整合提供了前瞻性观点，以推进精密气体医学领域的发展。

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引用次数: 0

Advances in hydrogen delivery strategies for therapeutic applications 治疗用氢输送策略的研究进展

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-11 DOI: 10.1016/j.addr.2025.115734

Lam-Duc-Huy Nguyen , Sheng-Yao Peng , Cam-Hoa Mac , Nhien Nguyen , Shih-Kai Lo , Po-Hsi Lin , Ninh-Son Pham , Hsiao-Huang Chang , Yu-Jung Lin , Hsing-Wen Sung

Molecular hydrogen (H₂) has emerged as a promising therapeutic agent owing to its selective antioxidant and anti-inflammatory properties, as well as its ability to modulate cellular signaling, metabolism, and immune responses. Beyond mitigating oxidative stress and inflammation, H₂ shows anticancer potential by altering the tumor microenvironment and inducing apoptosis. Despite encouraging findings from preclinical and clinical studies, conventional delivery routes—such as inhalation, oral intake of H₂-rich water, or injection of H₂-rich saline—face critical limitations in stability, bioavailability, and targeted delivery, impeding clinical translation. This review first outlines the therapeutic mechanisms of H₂, including redox regulation, inflammatory modulation, and tumor suppression. It then discusses current delivery approaches, their therapeutic outcomes, and inherent challenges. To overcome these barriers, a variety of advanced H₂-delivering systems have been developed, including H₂-containing carriers and in situ H₂-generating materials based on water-, acid-, and electrochemical reactions. Externally stimulated platforms, such as photo-, sono-, and electro-catalysis-based systems, enable spatiotemporally controlled H₂ release in response to disease-specific cues. Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H₂ delivery via gut fermentation. The review concludes by addressing key challenges—such as material scalability, biosafety, and integration with existing therapies—and highlights future directions for optimizing H₂ delivery through interdisciplinary innovation in materials science and medicine.

分子氢（H2）由于其选择性抗氧化和抗炎特性，以及调节细胞信号、代谢和免疫反应的能力，已成为一种有前途的治疗剂。除了减轻氧化应激和炎症外，H2还通过改变肿瘤微环境和诱导细胞凋亡显示出抗癌潜力。尽管临床前和临床研究取得了令人鼓舞的结果，但传统的给药途径——如吸入、口服富h2水或注射富h2盐——在稳定性、生物利用度和靶向给药方面存在严重局限性，阻碍了临床转化。本文首先概述了H2的治疗机制，包括氧化还原调节、炎症调节和肿瘤抑制。然后讨论了当前的递送方法，它们的治疗结果和固有的挑战。为了克服这些障碍，人们开发了各种先进的h2输送系统，包括含h2载体和基于水、酸和电化学反应的原位h2生成材料。外部刺激的平台，如基于光、声和电催化的系统，能够根据疾病特异性线索控制H2的时空释放。此外，针对微生物群的方法包括益生菌和益生元，通过肠道发酵提供间接但持续的H2输送。该综述总结了关键挑战，如材料可扩展性、生物安全性和与现有疗法的整合，并强调了通过材料科学和医学的跨学科创新优化氢气输送的未来方向。

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引用次数: 0

3D printing in theranostic applications 3D打印在治疗中的应用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-10 DOI: 10.1016/j.addr.2025.115733

Italo Rodrigo Calori, Ana Paula Pereira Guimaraes, Antonio Claudio Tedesco

Additive manufacturing has revolutionized conventional fabrication techniques, enabling the design of advanced theranostic platforms that integrates diagnostic and therapeutic functions within a single device. In this context, three-dimensional (3D) printing has emerged as a key technology for fabricating sophisticated theranostic solutions capable of effectively integrating diagnostic and therapeutic approaches. This review summarizes the recent use of 3D printing technologies in the field of theranostic, providing a comprehensive understanding of the state of the art and future perspectives. This review explores the design and fabrication of theranostic devices using a range of extrusion-based and light-based printing techniques including fused deposition modeling, stereolithography, and selective laser sintering. Furthermore, this review discuss the current challenges and limitations of the implementation of these technologies. Overall, this review provides insights into the potential and challenges of 3D printing for the advancement of theranostic strategies.

增材制造已经改变了传统的治疗方法，允许生产更复杂的设备，以满足不断发展的诊断和治疗需求。在这种情况下，三维（3D）打印已经成为生产个性化治疗的关键技术，能够有效地整合诊断和治疗方法。本文综述了近年来3D打印技术在治疗领域的应用，提供了对该技术现状和未来前景的全面了解。这篇综述探讨了使用一系列技术的治疗装置的设计和制造，包括基于挤压的印刷，熔融沉积建模，立体光刻和选择性激光烧结。此外，本综述还讨论了这些技术实施的当前挑战和局限性。最后，这篇综述提供了对3D打印的潜力和挑战的见解，以促进治疗策略。

引用次数: 0

Advanced adhesion and targeting strategies to prolong gut residence time and improve eLBP efficacy in colonic diseases 先进的粘附和靶向策略，延长肠道停留时间，提高eLBP在结肠疾病中的疗效。

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-10-22 DOI: 10.1016/j.addr.2025.115722

Alita F. Miller , Sri Sruthi Potluru , Sarah M. Thormann , Yuyan Wang , Juliane Nguyen

Engineered live biotherapeutic products (eLBPs) are genetically modified microorganisms being explored as a novel treatment modality for gastrointestinal (GI) diseases. The therapeutic potential is driven by their ability to selectively interact with host tissues while maintaining inherent probiotic properties that promote gut health. A key limitation of orally administered eLBPs is their poor competitive fitness against resident gut microbes, which often leads to rapid passage through the GI tract and reduced therapeutic efficacy. This challenge can be addressed by engineering eLBPs to extend their residence time in the gut and enhance the precision of therapeutic delivery at the target site. Targeted adhesion is a prevalent mechanism by which eLBPs achieve increased retention within the GI tract. Various targets in the colon have been used as anchors for non-resident microbes such as mucus, the extracellular matrix, and tumorous tissues. Additionally, a range of strategies have been explored for microbial targeting, including chemical surface modifications, genetically engineered surface display systems, metabolic engineering, and stimuli-responsive approaches. In this review, we provide insights into targets and targeting strategies that have been implemented in eLBP development and highlight the gaps that must be addressed to enhance eLBP efficacy through prolonged gut retention. We discuss the development of novel eLBP strains that target various components within healthy or diseased colon tissues for improved efficacy, particularly for inflammatory bowel disease and colorectal cancer. We conclude by detailing perspectives on eLBP design for clinically viable and effective therapeutics.

工程活生物治疗产品（elbp）是一种转基因微生物，正在被探索作为一种新的治疗胃肠道疾病的方式。治疗潜力是由它们选择性地与宿主组织相互作用的能力驱动的，同时保持促进肠道健康的固有益生菌特性。口服elbp的一个关键限制是它们与常驻肠道微生物的竞争适应性差，这通常导致快速通过胃肠道并降低治疗效果。这一挑战可以通过设计elbp来解决，以延长其在肠道中的停留时间，并提高靶向部位的治疗递送精度。靶向黏附是elbp在胃肠道内增加滞留的普遍机制。结肠中的各种靶点已被用作非常驻微生物（如粘液、细胞外基质和肿瘤组织）的锚点。此外，已经探索了一系列针对微生物的策略，包括化学表面修饰，基因工程表面显示系统，代谢工程和刺激响应方法。在这篇综述中，我们提供了在eLBP开发中实施的靶点和靶向策略的见解，并强调了通过延长肠道保留来提高eLBP疗效必须解决的差距。我们讨论了新型eLBP菌株的发展，这些菌株针对健康或患病结肠组织中的各种成分，以提高疗效，特别是对炎症性肠病和结直肠癌。最后，我们详细阐述了eLBP设计在临床上可行和有效的治疗方法。

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引用次数: 0

Investigating the restriction-modification barrier to DNA delivery in human gut probiotic bacteria for streamlined genetic tool development 研究人类肠道益生菌DNA传递的限制性修饰屏障，以促进流线型遗传工具的开发。

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-10-21 DOI: 10.1016/j.addr.2025.115723

Qiaochu Li , Ibrahim Al’ Abri , Nathan Crook , Justin M. Vento

Human gut bacteria have the potential to serve as next-generation therapeutics to many disease conditions, although poor genetic tractability limits mechanistic understanding and engineering capabilities in most strains. A major barrier to genetic tool development is bacterial defense systems such as the highly abundant restriction-modification systems that restrict DNA transformed into the cell. Although these systems are well-known barriers to DNA delivery across bacteria, their prevalence and diversity within probiotic human gut species has not been investigated. In this review, we detail the importance of DNA delivery in establishing genetic tools in bacteria and illustrate the role of restriction-modification systems in preventing DNA delivery. We then perform a computational analysis of available sequencing data to compile restriction-modification abundance and complexity in many human gut species with large probiotic potential. Through this analysis, we elucidate the large number of restriction-modification systems present in many species and highlight the diversity of restriction-modification systems in closely related strains. Among the four main types of restriction-modification systems, we pinpoint the main type(s) present in different species. To highlight strains with high potential to inhibit DNA delivery, we determine the percentage of strains from each species with multiple restriction-modification systems present. Finally, we cover established methods of bypassing the restriction-modification barrier to DNA delivery. Overall, this generalizable analysis should help others extend DNA delivery to more relevant strains across human gut bacteria to establish next generation living therapeutics from a wider range of probiotic strains.

人类肠道细菌有潜力作为许多疾病的下一代治疗药物，尽管在大多数菌株中，较差的遗传易感性限制了对其机制的理解和工程能力。遗传工具开发的一个主要障碍是细菌防御系统，如高度丰富的限制修饰系统，限制DNA转化为细胞。虽然这些系统是众所周知的细菌之间DNA传递的障碍，但它们在益生菌人类肠道物种中的患病率和多样性尚未得到调查。在这篇综述中，我们详细介绍了DNA传递在细菌中建立遗传工具的重要性，并说明了限制性修饰系统在防止DNA传递中的作用。然后，我们对现有的测序数据进行计算分析，以编制具有巨大益生菌潜力的许多人类肠道物种的限制性修饰丰度和复杂性。通过这一分析，我们阐明了许多物种中存在的大量限制性修饰系统，并突出了密切相关菌株中限制性修饰系统的多样性。在四种主要的限制修饰系统类型中，我们确定了不同物种中存在的主要类型。为了突出具有高抑制DNA传递潜力的菌株，我们确定了每个物种中存在多个限制性修饰系统的菌株的百分比。最后，我们介绍了绕过DNA递送的限制性修饰屏障的既定方法。总的来说，这种可推广的分析应该有助于其他人将DNA传递扩展到人类肠道细菌中更多相关的菌株，从而从更广泛的益生菌菌株中建立下一代活疗法。

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引用次数: 0

The complex and intricate relationship between incremental science, innovation and recognition 渐进式科学、创新和认可之间复杂而错综的关系

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-10-19 DOI: 10.1016/j.addr.2025.115721

Charlotte A. Birkmanis , David W. Grainger , Dietmar W. Hutmacher

Science, technology, and innovation are related but distinct, leading to different research incentives. Incremental science, such as refining methods and validating findings, ensures robust results and understanding, laying the groundwork for breakthroughs. Due to pressures for ongoing innovation, fundamental research is frequently seen as an obstacle hindering scientific progress instead of an investment. The time fundamental research requires to bear fruit can detract from its immediate relevance, and impatience surrounding the urgency for rapid innovation further devalues the relatively slow, methodical approach of basic science. But this emphasis can be misleading, as many crucial advances arise from incremental improvements or refinements rather than radical breakthroughs. Insisting on scientific novelty devalues the work that lays the essential groundwork for reliable scientific progress and endorses a culture where only the most sensational achievements are celebrated, marginalising the essential contributions of those engaged in less glamorous, yet equally important, foundational research. We argue that instead of focusing on celebrating novelty and its often-unrealised societal impacts, science and technology should better value more vital basic, incremental, and knowledge-based contributions necessary for sustaining innovation and ensuring its diverse, positive impacts.

科学、技术和创新相互关联，但又截然不同，这导致了不同的研究激励机制。渐进式科学，如改进方法和验证发现，确保了可靠的结果和理解，为突破奠定了基础。由于不断创新的压力，基础研究经常被视为阻碍科学进步的障碍，而不是一项投资。基础研究取得成果所需的时间可能会减损其直接相关性，而围绕快速创新的紧迫性的不耐烦进一步贬低了基础科学相对缓慢、有条不紊的方法。但这种强调可能会产生误导，因为许多关键的进步来自于渐进式的改进或改进，而不是根本性的突破。坚持科学的新颖性贬低了为可靠的科学进步奠定基本基础的工作，支持了一种只庆祝最轰动的成就的文化，边缘化了那些从事不那么光鲜但同样重要的基础研究的人的重要贡献。我们认为，科学和技术不应该专注于庆祝新奇事物及其往往未实现的社会影响，而应该更好地重视更重要的基础、增量和基于知识的贡献，这些贡献是维持创新和确保其多样化、积极影响所必需的。

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引用次数: 0

Hydrogen sulfide in cancer therapy: Intelligent delivery platforms and synergistic therapeutic paradigms 硫化氢在癌症治疗中的应用：智能输送平台和协同治疗范例

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-10-17 DOI: 10.1016/j.addr.2025.115717

Nailin Yang , Yichi Cai , Shumin Sun , Jihu Nie , Fei Gong , Zifan Pei , Liang Cheng

Hydrogen sulfide (H₂S) has emerged as a pivotal gaseous signaling molecule in cancer therapy, demonstrating unique dose-dependent therapeutic effects that have established new paradigms for gas-mediated treatments. To enable precise H₂S delivery in cancer therapy, various H₂S donor compounds have been developed, and a range of intelligent delivery systems have been subsequently designed. These systems are capable of specifically accumulating at tumor sites and can release H₂S in a controlled and responsive manner within the tumor microenvironment (TME). This comprehensive review systematically examines the fundamental physicochemical properties and multifaceted biological functions of H₂S while providing a detailed classification of H₂S donors into inorganic and organic categories. We further classify existing H₂S delivery strategies into endogenous-responsive systems (e.g., pH-, GSH-, and enzyme-triggered systems) and exogenous-responsive approaches (e.g., light-, ultrasound-, and electric field-activated methods), supported by representative case studies. Above all, this review highlights the remarkable potential of H₂S in enhancing various therapeutic modalities, including radiotherapy, chemotherapy, thermotherapy, catalytic therapy, and immunotherapy, primarily through its regulatory effects on heat shock protein expression, catalase activity modulation, and profound TME remodeling, which provides valuable insights for designing next-generation H₂S delivery systems and their combinatorial applications in cancer treatments.

硫化氢（H2S）已成为癌症治疗中关键的气体信号分子，其独特的剂量依赖性治疗效果为气体介导治疗建立了新的范例。为了在癌症治疗中实现H2S的精确输送，已经开发了各种H2S供体化合物，并随后设计了一系列智能输送系统。这些系统能够在肿瘤部位特异性积累，并在肿瘤微环境（TME）中以可控和响应的方式释放H2S。这篇综合综述系统地研究了H2S的基本物理化学性质和多方面的生物学功能，同时详细地将H2S供体分为无机和有机两类。我们进一步将现有的H2S输送策略分为内源响应系统（如pH-、GSH-和酶触发系统）和外源响应方法（如光、超声和电场激活方法），并通过代表性案例研究进行了支持。总之，这篇综述强调了H2S在增强各种治疗方式（包括放疗、化疗、热疗法、催化疗法和免疫疗法）方面的显著潜力，主要是通过其对热休克蛋白表达、过氧化氢酶活性调节和深度TME重塑的调节作用，这为设计下一代H2S输送系统及其在癌症治疗中的组合应用提供了有价值的见解。

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引用次数: 0

Microbiome-active drug delivery systems (MADDS): Leveraging microbial stimuli for controlled drug release 微生物活性药物传递系统（MADDS）：利用微生物刺激控制药物释放

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-10-15 DOI: 10.1016/j.addr.2025.115720

Srinivas Kamath , Amin Ariaee , Amer Abdelhafez, Zarnab Asif, Nicole S.L. Chan, Kate Collins, Alexander Hunter, Paul Joyce

The human microbiome comprises diverse microbial communities that inhabit tissues and biofluids throughout the body, including the gastrointestinal tract, lungs, vagina, and skin. These sites create dynamic microenvironments rich in enzymes, metabolites, and chemical gradients that act both as biological barriers and as localised targets for drug delivery. This review provides an overview of Microbiome-Active Drug Delivery Systems (MADDS), an emerging class of platforms that exploit microbial stimuli for site-specific therapeutic release. Unlike conventional systems that simply coexist with the microbiome, MADDS harness resident microbes and their metabolites to trigger drug activation, retention, or release. This enables spatially precise delivery of small molecules, biologics, and live biotherapeutic products (LBPs). Key strategies include enzyme-, environment-, metabolite-, biofilm-, and receptor-responsive designs, each tailored to microbial niches and applied across infectious, inflammatory, and metabolic disorders. However, challenges remain, including microbiome variability between individuals, regulatory uncertainty around hybrid biologic-material systems, and the need for scalable GMP-compliant manufacturing. This review therefore outlines the current approaches for engineering MADDS and the future steps required for clinical translation. By exploiting microbial cues for controlled drug release, MADDS offer a practical route to more targeted and patient-specific therapies.

人体微生物组包括居住在整个身体的组织和生物流体中的多种微生物群落，包括胃肠道、肺、阴道和皮肤。这些位点创造了富含酶、代谢物和化学梯度的动态微环境，这些微环境既可以作为生物屏障，也可以作为药物递送的局部靶点。这篇综述提供了微生物活性药物传递系统（MADDS）的概述，这是一类新兴的利用微生物刺激进行特定部位治疗释放的平台。与简单地与微生物组共存的传统系统不同，MADDS利用常驻微生物及其代谢物来触发药物激活、保留或释放。这使得小分子、生物制剂和活体生物治疗产品（lbp）的空间精确递送成为可能。关键策略包括酶、环境、代谢物、生物膜和受体响应设计，每种设计都针对微生物生态位进行定制，并适用于感染性、炎症性和代谢性疾病。然而，挑战仍然存在，包括个体之间微生物组的可变性，混合生物材料系统的监管不确定性，以及对可扩展的gmp合规生产的需求。因此，这篇综述概述了目前工程MADDS的方法和临床转化所需的未来步骤。通过利用微生物线索控制药物释放，MADDS为更有针对性和患者特异性的治疗提供了一条实用的途径。

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引用次数: 0