Advanced drug delivery reviews最新文献_第4页

GMP-compliant manufacturing of iPSC-derived therapeutic cell products: Technologies, applications, risks and limitations ipsc衍生治疗细胞产品的gmp合规生产：技术、应用、风险和限制

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-02 DOI: 10.1016/j.addr.2025.115744

Alexandra Haase, Arjang Ruhparwar, Ulrich Martin

The development of induced pluripotent stem cells (iPSCs) has transformed the field of regenerative medicine. However, to use iPSCs for therapeutic applications, iPSC-based products must be produced under Good Manufacturing Practice (GMP) conditions. This process involves reprogramming somatic cells, characterizing and banking iPSC lines, introducing therapeutic transgenes if necessary, and scaling up cell expansion and differentiation for clinical use. This review provides an overview of the relevant regulatory authorities and relevant regulations in the US, Europe, and Japan. It also discusses the current challenges and opportunities in producing GMP-compliant iPSCs. These challenges include the need for defined culture media, as well as developing all the required GMP-compliant processes, such as reprogramming, establishing iPSC clones, and manufacturing processes that lead to the final advanced therapy medicinal product (ATMP). For autologous products in particular, this can be complicated by cell line-specific variation of proliferation velocity and differentiation biases. The review also discusses attempts to develop automated closed systems. It emphasizes the importance of ensuring the sterility, identity, (epi)genetic integrity, and functionality of the final cell products to guarantee the safety and the efficacy of iPSC-based therapies. However, the need for reproducibility, rigorous quality control and safety requirements has resulted in high regulatory hurdles and extremely high costs, which often prevent the initiation of clinical trials. Overcoming these challenges will enable iPSCs to play an integral role in future medicine and offer new treatment options for various diseases.

诱导多能干细胞（iPSCs）的发展已经改变了再生医学领域。然而，要将ipsc用于治疗应用，基于ipsc的产品必须在良好生产规范（GMP）条件下生产。这一过程包括对体细胞进行重编程，鉴定和储存iPSC系，必要时引入治疗性转基因，扩大细胞扩增和分化以供临床使用。本综述概述了美国、欧洲和日本的相关监管机构和相关法规。它还讨论了生产符合gmp的iPSCs的当前挑战和机遇。这些挑战包括需要明确的培养基，以及开发所有必需的符合gmp的流程，例如重编程，建立iPSC克隆，以及导致最终先进治疗药物产品（ATMP）的制造流程。特别是对于自体产物，这可能会因细胞系特异性增殖速度和分化偏差的变化而变得复杂。该评论还讨论了开发自动化封闭系统的尝试。它强调了确保最终细胞产品的无菌性、身份、（epi）遗传完整性和功能的重要性，以确保基于ipsc的治疗的安全性和有效性。然而，对可重复性、严格的质量控制和安全要求的需要导致了很高的监管障碍和极高的成本，这往往阻碍了临床试验的开展。克服这些挑战将使多能干细胞在未来医学中发挥不可或缺的作用，并为各种疾病提供新的治疗选择。

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引用次数: 0

Implications of genetic and epigenetic aberrations to the tumorigenicity of human pluripotent stem cells 遗传和表观遗传畸变对人类多能干细胞致瘤性的影响

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-29 DOI: 10.1016/j.addr.2025.115743

Gal Keshet , Ivana Barbaric , Nissim Benvenisty

Human pluripotent stem cells (hPSCs) hold immense promise for cell replacement therapies due to their capacity to give rise to derivatives of the three embryonic germ layers and their ability to divide indefinitely in culture. Since their first derivation less than 30 years ago, multiple hPSC-derived cell products are already in clinical trials for a range of pathologies. Nevertheless, hPSCs also possess an intrinsic tumorigenic potential and have been shown to acquire recurrent genetic and epigenetic aberrations strongly associated with cancer initiation and progression. These properties cast doubt on the safety of hPSCs and raise concerns regarding their use for transplantation. In this review, we summarize the different kinds of genetic and epigenetic abnormalities repeatedly observed in hPSCs, how they emerge, and their potential implications for the tumorigenicity of hPSC-based products. We also discuss shared and unique abnormalities found in hPSCs derived from different sources. Finally, we suggest possible methods for reducing the occurrence of these aberrations and managing their effects once they arise.

人类多能干细胞（hPSCs）由于其能够产生三种胚胎胚层的衍生物以及在培养中无限分裂的能力，在细胞替代疗法中具有巨大的前景。自不到30年前首次衍生以来，多种hpsc衍生的细胞产品已经在一系列病理的临床试验中。然而，hPSCs也具有内在的致瘤潜能，并且已被证明获得与癌症发生和进展密切相关的复发性遗传和表观遗传畸变。这些特性使人怀疑造血干细胞的安全性，并引起对其用于移植的关注。在这篇综述中，我们总结了在人造血干细胞中反复观察到的不同类型的遗传和表观遗传异常，它们是如何出现的，以及它们对基于人造血干细胞的产品的致瘤性的潜在影响。我们还讨论了在不同来源的人造血干细胞中发现的共同和独特的异常。最后，我们提出了可能的方法，以减少这些畸变的发生和管理他们的影响，一旦他们出现。

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引用次数: 0

Microbial heterogeneity-mediated treatment evasion and the potential for engineered live biotherapeutic products 微生物异质性介导的治疗逃避和工程活生物治疗产品的潜力

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-28 DOI: 10.1016/j.addr.2025.115740

Eli G. Cytrynbaum , Megan N. McClean

Microbial populations exhibit both genetic and non-genetic heterogeneity. In the clinical context, this heterogeneity is of concern as it provides subsets of microbial populations with enhanced immune evasion abilities and antimicrobial resistance. Fungal pathogens are of special concern as fungal diseases and antifungal resistance are increasing worldwide and similarities between eukaryotic cells make it challenging to identify targets that are toxic to fungi without also harming the human host. Engineered live biotherapeutic products (eLBPs) could provide an alternative and complementary approach to manipulating and treating heterogeneous fungal populations due to their potential to provide localized delivery to the affected site, continuous long-term treatment, environmental sensing, and delivery of therapeutics specific to virulent or drug-resistant organisms. However, the development of eLBPs targeting fungi remains limited.

This review assesses our current understanding of genetic and non-genetic microbial heterogeneity and how this impacts treatment strategies particularly for pathogenic fungi. We focus on Candida yeasts, specifically Candida albicans, as Candida species are the most common opportunistic fungal pathogens. We review the current scope and potential of eLBPs to address heterogeneous and rising fungal infections.

微生物种群表现出遗传和非遗传异质性。在临床环境中，这种异质性值得关注，因为它提供了具有增强的免疫逃避能力和抗菌素耐药性的微生物种群亚群。真菌病原体受到特别关注，因为真菌疾病和抗真菌耐药性在世界范围内日益增加，真核细胞之间的相似性使得鉴定对真菌有毒而又不伤害人类宿主的靶标具有挑战性。工程活生物治疗产品（elbp）可以提供一种替代和补充的方法来操纵和治疗异质真菌群体，因为它们有可能提供局部递送到受影响的部位，持续的长期治疗，环境传感，以及递送针对有毒或耐药生物的治疗药物。然而，针对真菌的elbp的开发仍然有限。这篇综述评估了我们目前对遗传和非遗传微生物异质性的理解，以及这如何影响治疗策略，特别是对致病真菌。我们专注于念珠菌酵母菌，特别是白色念珠菌，因为念珠菌是最常见的机会性真菌病原体。我们回顾了elbp目前的范围和潜力，以解决异质性和上升的真菌感染。

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引用次数: 0

Guiding design and performance of nonviral nucleic acid delivery vehicles via machine learning 通过机器学习指导非病毒核酸运载工具的设计和性能

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-24 DOI: 10.1016/j.addr.2025.115739

John A. Hutchinson , Sidharth Panda , Plinio D. Rosales , Janey P. Sowada , Miles S. Willis , Michael C. Leyden , Prodromos Daoutidis , Theresa M. Reineke

Machine Learning (ML) techniques have enabled the advancement of many technologies throughout the pharmaceutical industry, especially for drug discovery. One of the most rapidly growing technologies within the pharmaceutical space is gene therapy, with twenty six FDA-approved genetic medicines and over three thousand treatments currently undergoing clinical trials. A key challenge in the successful employment of gene therapy is effective nucleic acid delivery, and nonviral delivery vectors provide a cost-effective and highly customizable solution to this challenge. However, the vast design space also poses a large challenge for traditional development, which relies heavily on iterative trial-and-error and costly in vivo and in vitro experiments. This review identifies key ML techniques and discusses how these approaches have been utilized to improve the design of nonviral nucleic acid delivery vehicles. ML has the potential to radically transform the design space for nucleic acid therapies, like it has already done in drug discovery and drug formulations. This potential is being realized in research and has already led to the advent of several commercial enterprises seeking to build full end-to-end platforms for rapidly decreasing development time for new gene therapies.

机器学习（ML）技术使制药行业的许多技术取得了进步，特别是在药物发现方面。基因治疗是制药领域发展最快的技术之一，目前有26种fda批准的基因药物和3000多种治疗方法正在进行临床试验。成功使用基因疗法的一个关键挑战是有效的核酸递送，而非病毒递送载体为这一挑战提供了一种成本效益高且高度可定制的解决方案。然而，巨大的设计空间也给传统的开发带来了巨大的挑战，传统的开发严重依赖于反复的试错和昂贵的体内和体外实验。这篇综述确定了关键的ML技术，并讨论了如何利用这些方法来改进非病毒核酸递送载体的设计。ML有可能从根本上改变核酸疗法的设计空间，就像它已经在药物发现和药物配方中所做的那样。这种潜力正在研究中得到实现，并且已经导致一些商业企业寻求建立完整的端到端平台，以快速缩短新基因疗法的开发时间。

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引用次数: 0

Advanced oral therapies for colorectal cancer via nanomedicine and microbiota modulation 通过纳米药物和微生物群调节治疗结直肠癌的先进口服疗法

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-22 DOI: 10.1016/j.addr.2025.115741

Yu Wang , Cheng Chen , Xin Xiao , Yajing Kang , Jinhan He , Ana Beloqui , Yining Xu

Colorectal cancer (CRC) is the third most common malignancy and the second most lethal cancer worldwide and has become a significant burden on global healthcare. The primary treatments for CRC include surgery, chemotherapy, and targeted therapy. However, these approaches face several limitations, such as invasive administration, poor patient compliance, systemic toxicity, drug resistance, and recurrence. Thus, alternative therapeutic strategies to overcome these challenges are urgently needed. Oral administration represents a promising approach for CRC treatment because of its noninvasive nature, safety, ease of self-administration, and high patient compliance. Moreover, when applied in CRC treatment, oral therapies can potentially increase therapeutic efficacy and reduce systemic toxicity via local treatment. Furthermore, the unique pathophysiological features of CRC, such as the overexpression of certain receptors and dysbiosis, present valuable opportunities for the development of advanced oral therapies. This review focuses on cutting-edge oral therapies for CRC, including nanomedicine-based and bacteria-modulating strategies. These approaches show significant promise for improving therapeutic outcomes and can be combined with existing treatment modalities to improve efficacy and minimize adverse effects. Additionally, we provide critical perspectives on the challenges and future perspectives of these strategies for CRC management. This review aims to provide novel insights into the design and advancement of oral therapies, paving the way for more effective and patient-friendly CRC treatments.

结直肠癌（CRC）是全球第三大常见恶性肿瘤和第二大致命癌症，已成为全球医疗保健的重大负担。结直肠癌的主要治疗包括手术、化疗和靶向治疗。然而，这些方法面临一些限制，如侵入性给药、患者依从性差、全身毒性、耐药性和复发。因此，迫切需要替代治疗策略来克服这些挑战。口服给药是非侵入性的、安全的、易于自我给药和患者的高依从性是治疗结直肠癌的一种很有前途的方法。此外，当应用于结直肠癌治疗时，口服疗法可以通过局部治疗潜在地提高治疗效果并减少全身毒性。此外，CRC独特的病理生理特征，如某些受体的过表达和生态失调，为开发先进的口服治疗提供了宝贵的机会。本文综述了CRC的前沿口服治疗方法，包括纳米药物和细菌调节策略。这些方法显示出改善治疗结果的重大希望，并可与现有治疗方式相结合，以提高疗效并最大限度地减少不良反应。此外，我们还就这些策略对CRC管理的挑战和未来前景提供了关键观点。本综述旨在为口服治疗的设计和进展提供新的见解，为更有效和患者友好的结直肠癌治疗铺平道路。

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引用次数: 0

Red to near-infrared carbon dots: synthesis, cellular interactions, drug loading, and therapeutic applications 红到近红外碳点：合成，细胞相互作用，药物装载和治疗应用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-22 DOI: 10.1016/j.addr.2025.115742

Pooria Lesani , Iman Zare , Mansi Khetarpaul , Zufu Lu , Azadeh Ghaee , Hala Zreiqat

The emergence of nanoparticles (NPs) has profoundly revolutionized targeted drug delivery systems, overcoming numerous limitations associated with conventional therapies. Red to near-infrared (NIR) emissive carbon dots (RNCDs) have emerged as promising theranostic candidates owing to their unique combination of superior photophysical properties, including high quantum yield (QY) and photostability, and excellent biocompatibility. This review provides a comprehensive examination of the synthesis methods of RNCDs, with a particular focus on the bottom-up approach. We explore how variations in precursor selection, solvent type, heteroatom doping, and thermal conditions influence the photophysical characteristics of RNCDs. Furthermore, we have analysed strategies for drug loading, targeting mechanisms (both passive and active), and cellular uptake pathways, highlighting methodologies employed to enhance therapeutic efficacy. The review also assesses the specific applications of RNCDs in cancer therapy and microbial infection treatments, focusing on their biocompatibility, reduced systemic phototoxicity, and minimal autofluorescence interference. Lastly, we discuss controlled drug release mechanisms, including pH-responsive, redox-sensitive, and photothermal systems, that enable controlled release profiles.

纳米颗粒（NPs）的出现彻底改变了靶向给药系统，克服了传统疗法的许多局限性。红至近红外（NIR）发射碳点（RNCDs）由于其独特的光物理特性，包括高量子产率和光稳定性，以及出色的生物相容性，已成为有希望的治疗候选者。本文综述了RNCDs合成方法的全面研究，特别侧重于自下而上的方法。我们探讨了前驱体选择、溶剂类型、杂原子掺杂和热条件的变化如何影响RNCDs的光物理特性。此外，我们还分析了药物装载、靶向机制（被动和主动）和细胞摄取途径的策略，强调了用于提高治疗效果的方法。综述还评估了RNCDs在癌症治疗和微生物感染治疗中的具体应用，重点是它们的生物相容性、降低全身光毒性和最小的自身荧光干扰。最后，我们讨论了控制药物释放机制，包括ph响应，氧化还原敏感和光热系统，使控制释放概况。

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引用次数: 0

Informing development of brain cancer therapies within "preclinical trials" using ex vivo patient tumors 为使用离体患者肿瘤进行“临床前试验”的脑癌治疗提供信息

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-11-19 DOI: 10.1016/j.addr.2025.115736

Adebimpe Adefolaju , David E. Kram , Breanna Mann , Shawn Hingtgen , Andrew Satterlee

Brain and nervous system cancers account for only ∼1.3% of new cancer diagnoses but rank ninth in US cancer mortality, a disparity partly driven by limited therapeutic options and inadequate preclinical models that misrepresent a drug’s therapeutic potential. Considering that about 90% of drugs validated with these models fail in late-phase clinical trials, it is imperative to further scrutinize drugs in preclinical settings that better model relevant aspects of disease and treatment response. New paradigms must account for challenges unique to brain cancers such as lack of relevant biomarkers and both intra-disease and patient to patient heterogeneity, which cause treatments to be effective in a suboptimal proportion of the population. In this review, we investigate the current brain cancer drug development landscape, introduce a growing field of functional precision medicine, and propose the inclusion of “preclinical trials” that interrogate the effects of new therapies and drug delivery mechanisms on living patient tumors ex vivo. These preclinical trials respond to the FDA’s recent announcement to phase out and replace live animal testing with human-based lab models. Functional models can address heterogeneity and biomarker identification through accrual of living patient tumor tissue, preclinical drug sensitivity testing, identification of non-responders and resistance mechanisms, and development of functional predictive biomarkers and companion diagnostics. Because functional precision medicine stratification of clinical trials candidates has shown improved clinical trials outcome, using this paradigm earlier in drug development could enhance clinical trial success, leading to more FDA-approved drugs and therapeutic options for brain cancer patients.

脑和神经系统癌症仅占新癌症诊断的约1.3%，但在美国癌症死亡率中排名第九，这一差距的部分原因是有限的治疗选择和不充分的临床前模型，这些模型错误地反映了药物的治疗潜力。考虑到使用这些模型验证的药物中约有90%在后期临床试验中失败，因此有必要进一步审查临床前环境中的药物，以便更好地模拟疾病和治疗反应的相关方面。新的范式必须考虑脑癌特有的挑战，如缺乏相关的生物标志物，以及疾病内和患者之间的异质性，这导致治疗在人口的次优比例中有效。在这篇综述中，我们调查了目前脑癌药物的开发前景，介绍了一个不断发展的功能精准医学领域，并提出了包括“临床前试验”在内的新疗法和药物给药机制对活体肿瘤患者的影响。这些临床前试验是对FDA最近宣布逐步淘汰并用基于人类的实验室模型取代活体动物试验的回应。功能模型可以通过活体患者肿瘤组织的累积、临床前药物敏感性测试、无反应和耐药机制的识别以及功能预测性生物标志物和伴随诊断的发展来解决异质性和生物标志物鉴定。由于对临床试验候选者的功能精准医学分层已经显示出改善的临床试验结果，在药物开发的早期使用这种模式可以提高临床试验的成功率，从而为脑癌患者带来更多fda批准的药物和治疗选择。

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引用次数: 0

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