Advanced drug delivery reviews最新文献_第9页

Classic versus innovative strategies for immuno-therapy in pancreatic cancer 胰腺癌免疫治疗的经典与创新策略

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-08-07 DOI: 10.1016/j.addr.2025.115671

Maria Giovanna Formelli , Andrea Palloni , Simona Tavolari , Chiara Deiana , Elisa Andrini , Mariacristina Di Marco , Davide Campana , Giuseppe Lamberti , Giovanni Brandi

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Immunotherapy with immune checkpoint inhibitors (ICIs), either as monotherapy, in combination with other ICIs, or alongside chemotherapy, has significantly improved outcomes in several solid tumors. However, its efficacy in PDAC remains limited due to multiple resistance mechanisms.

Key determinants of immunotherapy resistance in PDAC include physical barriers that hinder immune cells infiltration, such as aberrant vasculature, cancer-associated fibroblasts (CAFs), and excessive hyaluronic acid deposition in the tumor microenvironment (TME). Additionally, PDAC is characterized by an immunosuppressive TME enriched with regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and by low immunogenicity of tumor cells due to KRAS mutations, MYC overexpression, and a low tumor mutational burden, further impairing antitumor immunity.

This review discusses advanced drug delivery systems to overcome determinants of immunotherapy resistance and to improve outcomes, explores emerging immunotherapy strategies, including adoptive cell therapies, cancer vaccines, and the potential role of microbiota as modulator of TME through fecal microbiota transplantation or intratumoral bacterial inoculation. Given the ambivalent role of microbiota in PDAC, the need for a clear definition of favorable strains and their selection is highlighted. Emerging approaches involving engineered bacteria and artificial intelligence applications are also explored.

Finally, we propose a hypothetical conceptual framework for an innovative multimodal immunotherapy approach to overcome resistance and improve clinical outcomes in PDAC.

胰腺导管腺癌（PDAC）是一种预后不佳的侵袭性恶性肿瘤。免疫检查点抑制剂（ICIs）的免疫治疗，无论是单独治疗，与其他ICIs联合治疗，还是与化疗联合治疗，都能显著改善几种实体瘤的预后。然而，由于多种耐药机制，其在PDAC中的疗效仍然有限。PDAC免疫治疗耐药的关键决定因素包括阻碍免疫细胞浸润的物理屏障，如异常的脉管系统、癌症相关成纤维细胞（CAFs）和肿瘤微环境（TME）中过多的透明质酸沉积。此外，PDAC的特点是免疫抑制性TME富集了调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs），并且由于KRAS突变、MYC过表达和低肿瘤突变负担，肿瘤细胞的免疫原性较低，进一步损害抗肿瘤免疫。这篇综述讨论了先进的药物输送系统，以克服免疫治疗耐药的决定因素并改善结果，探讨了新兴的免疫治疗策略，包括过继细胞疗法，癌症疫苗，以及通过粪便微生物群移植或肿瘤内细菌接种作为TME调节剂的微生物群的潜在作用。鉴于微生物群在PDAC中的矛盾作用，需要明确定义有利菌株及其选择。还探讨了涉及工程细菌和人工智能应用的新兴方法。最后，我们提出了一种创新的多模式免疫治疗方法的假设概念框架，以克服PDAC的耐药和改善临床结果。

{"title":"Classic versus innovative strategies for immuno-therapy in pancreatic cancer","authors":"Maria Giovanna Formelli , Andrea Palloni , Simona Tavolari , Chiara Deiana , Elisa Andrini , Mariacristina Di Marco , Davide Campana , Giuseppe Lamberti , Giovanni Brandi","doi":"10.1016/j.addr.2025.115671","DOIUrl":"10.1016/j.addr.2025.115671","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Immunotherapy with immune checkpoint inhibitors (ICIs), either as monotherapy, in combination with other ICIs, or alongside chemotherapy, has significantly improved outcomes in several solid tumors. However, its efficacy in PDAC remains limited due to multiple resistance mechanisms.</div><div>Key determinants of immunotherapy resistance in PDAC include physical barriers that hinder immune cells infiltration, such as aberrant vasculature, cancer-associated fibroblasts (CAFs), and excessive hyaluronic acid deposition in the tumor microenvironment (TME). Additionally, PDAC is characterized by an immunosuppressive TME enriched with regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and by low immunogenicity of tumor cells due to KRAS mutations, MYC overexpression, and a low tumor mutational burden, further impairing antitumor immunity.</div><div>This review discusses advanced drug delivery systems to overcome determinants of immunotherapy resistance and to improve outcomes, explores emerging immunotherapy strategies, including adoptive cell therapies, cancer vaccines, and the potential role of microbiota as modulator of TME through fecal microbiota transplantation or intratumoral bacterial inoculation. Given the ambivalent role of microbiota in PDAC, the need for a clear definition of favorable strains and their selection is highlighted. Emerging approaches involving engineered bacteria and artificial intelligence applications are also explored.</div><div>Finally, we propose a hypothetical conceptual framework for an innovative multimodal immunotherapy approach to overcome resistance and improve clinical outcomes in PDAC.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115671"},"PeriodicalIF":17.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patient-Derived 3D-Bioprinted Models of Pancreatic Cancer: Toward Personalized Therapy and Overcoming Tumor Microenvironment Challenges 胰腺癌患者衍生的3d生物打印模型：个性化治疗和克服肿瘤微环境挑战

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-08-07 DOI: 10.1016/j.addr.2025.115670

Daniella Vaskovich-Koubi , Marina Green Buzhor , Anne Krinsky , Yair Roth , Koren Salomon , Ron Kleiner , Rina Sevostianov , Ohad Hasin , Rami Khoury , Ronit Satchi-Fainaro

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-resistant solid tumors, mainly due to its complex tumor microenvironment (TME). Characterized by dense desmoplastic stroma, immune suppression, and metabolic rewiring, the TME impairs drug delivery and eventually leads to therapeutic failure. Conventional models, such as two-dimensional (2D) cultures and mouse models, fail to recapitulate the cellular and mechanical intricacies of PDAC, limiting their translational relevance.

Three-dimensional (3D) models have emerged as promising tools to better simulate tumor biology. Among them, 3D-bioprinting techniques enable the precise spatial organization of cancer, stromal, and immune cells within tailored bioinks, supporting physiologically relevant architectures and dynamic microenvironmental interactions. These platforms allow controlled incorporation of extracellular matrix components, tunable stiffness, and perfusable vasculature, improving model fidelity and enabling real-time assessment of drug penetration, immune infiltration, and therapy resistance.

This review provides a comprehensive overview of current 3D PDAC modeling strategies, emphasizing patient-derived 3D-bioprinted models. We explore the key roles of bioink composition, extracellular matrix (ECM) stiffness, perfusion capacity, and immuno-compatibility in shaping the fidelity and utility of these models. Furthermore, we compare the structural complexity, scalability, drug-screening capabilities, and applicability for personalized medicine of different 3D models. By highlighting advances in vascularization, immune co-culture, and biofabrication technologies, we underscore the emerging value of 3D-bioprinting as a transformative platform for preclinical PDAC research. Ultimately, 3D-bioprinting is an important step forward in bridging the gap between preclinical studies and clinical implementation, as it opens the door to more accurate, personalized, and efficient therapeutic approaches for PDAC.

胰腺导管腺癌（Pancreatic ductal adenocarcinoma， PDAC）是侵袭性最强、最难治疗的实体肿瘤之一，主要是由于其复杂的肿瘤微环境（tumor microenvironment， TME）。TME以致密的间质、免疫抑制和代谢重组为特征，损害药物传递并最终导致治疗失败。传统的模型，如二维培养和小鼠模型，不能概括PDAC的细胞和机械复杂性，限制了它们的翻译相关性。三维（3D）模型已经成为更好地模拟肿瘤生物学的有前途的工具。其中，3d生物打印技术能够在定制的生物墨水中精确地组织癌症、基质和免疫细胞，支持生理相关架构和动态微环境相互作用。这些平台可以控制细胞外基质成分的掺入，调节刚度和可灌注血管，提高模型保真度，并能够实时评估药物渗透、免疫浸润和治疗耐药性。这篇综述提供了当前3D PDAC建模策略的全面概述，强调患者衍生的3D生物打印模型。我们探讨了生物链接成分、ECM刚度、灌注能力和免疫相容性在塑造这些模型的保真度和实用性中的关键作用。此外，我们比较了不同3D模型的结构复杂性、可扩展性、药物筛选能力和个性化医疗的适用性。通过强调血管化、免疫共培养和生物制造技术的进步，我们强调了3d生物打印作为临床前PDAC研究的变革性平台的新兴价值。最终，3d生物打印是弥合临床前研究和临床实施之间差距的重要一步，因为它为PDAC的更准确，个性化和有效的治疗方法打开了大门。

{"title":"Patient-Derived 3D-Bioprinted Models of Pancreatic Cancer: Toward Personalized Therapy and Overcoming Tumor Microenvironment Challenges","authors":"Daniella Vaskovich-Koubi , Marina Green Buzhor , Anne Krinsky , Yair Roth , Koren Salomon , Ron Kleiner , Rina Sevostianov , Ohad Hasin , Rami Khoury , Ronit Satchi-Fainaro","doi":"10.1016/j.addr.2025.115670","DOIUrl":"10.1016/j.addr.2025.115670","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-resistant solid tumors, mainly due to its complex tumor microenvironment (TME). Characterized by dense desmoplastic stroma, immune suppression, and metabolic rewiring, the TME impairs drug delivery and eventually leads to therapeutic failure. Conventional models, such as two-dimensional (2D) cultures and mouse models, fail to recapitulate the cellular and mechanical intricacies of PDAC, limiting their translational relevance.</div><div>Three-dimensional (3D) models have emerged as promising tools to better simulate tumor biology. Among them, 3D-bioprinting techniques enable the precise spatial organization of cancer, stromal, and immune cells within tailored bioinks, supporting physiologically relevant architectures and dynamic microenvironmental interactions. These platforms allow controlled incorporation of extracellular matrix components, tunable stiffness, and perfusable vasculature, improving model fidelity and enabling real-time assessment of drug penetration, immune infiltration, and therapy resistance.</div><div>This review provides a comprehensive overview of current 3D PDAC modeling strategies, emphasizing patient-derived 3D-bioprinted models. We explore the key roles of bioink composition, extracellular matrix (ECM) stiffness, perfusion capacity, and immuno-compatibility in shaping the fidelity and utility of these models. Furthermore, we compare the structural complexity, scalability, drug-screening capabilities, and applicability for personalized medicine of different 3D models. By highlighting advances in vascularization, immune co-culture, and biofabrication technologies, we underscore the emerging value of 3D-bioprinting as a transformative platform for preclinical PDAC research. Ultimately, 3D-bioprinting is an important step forward in bridging the gap between preclinical studies and clinical implementation, as it opens the door to more accurate, personalized, and efficient therapeutic approaches for PDAC.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115670"},"PeriodicalIF":17.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinspired approaches to encapsulate and deliver bacterial live biotherapeutic products 生物启发的方法来封装和输送细菌活的生物治疗产品

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-08-06 DOI: 10.1016/j.addr.2025.115663

Noah Y. Brittain, Joel A. Finbloom

Bacteria-based therapies such as live biotherapeutic products (LBPs) allow for the in situ production of bioactive and therapeutic compounds, offering immense potential in the treatment of numerous diseases, including colitis, cancer, and metabolic diseases. While promising, LBPs face numerous delivery barriers that limit their translational potential. Many of these challenges stem from the specific requirements of delivering living bacteria, necessitating delivery systems with distinctive features beyond traditional drug delivery approaches. By taking inspiration from natural biological systems such as bacterial membranes, capsules, and biofilms, researchers can build upon fundamental biological insights combined with advances in materials science, chemical biology, and bioengineering to develop next-generation LBP delivery systems. In this review, we will cover the current progress in bacterial LBPs and major barriers to their delivery. We will then discuss in depth the different bioinspired LBP delivery systems that have been developed and highlight challenges that must be addressed for this nascent field to advance and achieve widespread clinical translation.

以细菌为基础的疗法，如活体生物治疗产品（lbp），允许生物活性和治疗性化合物的原位生产，在治疗多种疾病，包括结肠炎、癌症和代谢疾病方面提供了巨大的潜力。虽然前景光明，但lbp面临着许多限制其转化潜力的交付障碍。这些挑战中有许多来自于输送活细菌的特殊要求，这就需要比传统的药物输送方法具有独特特征的输送系统。通过从细菌膜、胶囊和生物膜等自然生物系统中获得灵感，研究人员可以结合材料科学、化学生物学和生物工程的进步，建立基本的生物学见解，开发下一代LBP传递系统。在这篇综述中，我们将介绍细菌lbp的最新进展及其传递的主要障碍。然后，我们将深入讨论已经开发的不同的生物启发LBP输送系统，并强调必须解决的挑战，以促进这一新兴领域的发展和实现广泛的临床转化。

{"title":"Bioinspired approaches to encapsulate and deliver bacterial live biotherapeutic products","authors":"Noah Y. Brittain, Joel A. Finbloom","doi":"10.1016/j.addr.2025.115663","DOIUrl":"10.1016/j.addr.2025.115663","url":null,"abstract":"<div><div>Bacteria-based therapies such as live biotherapeutic products (LBPs) allow for the <em>in situ</em> production of bioactive and therapeutic compounds, offering immense potential in the treatment of numerous diseases, including colitis, cancer, and metabolic diseases. While promising, LBPs face numerous delivery barriers that limit their translational potential. Many of these challenges stem from the specific requirements of delivering living bacteria, necessitating delivery systems with distinctive features beyond traditional drug delivery approaches. By taking inspiration from natural biological systems such as bacterial membranes, capsules, and biofilms, researchers can build upon fundamental biological insights combined with advances in materials science, chemical biology, and bioengineering to develop next-generation LBP delivery systems. In this review, we will cover the current progress in bacterial LBPs and major barriers to their delivery. We will then discuss in depth the different bioinspired LBP delivery systems that have been developed and highlight challenges that must be addressed for this nascent field to advance and achieve widespread clinical translation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115663"},"PeriodicalIF":17.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting population dynamics of antimicrobial resistance using mechanistic modeling and machine learning 利用机械建模和机器学习预测抗菌素耐药性的种群动态

IF 16.1 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-08-05 DOI: 10.1016/j.addr.2025.115661

Zhengqing Zhou, Irida Shyti, Jaemin Kim, Lingchong You

Antimicrobial resistance (AMR) infections have become a global public health burden. The pipeline for new antibiotic discovery is draining due to the rapid emergence of resistance to new antibiotics, the limited economic return, and regulatory hurdles. Current strategies to combat the AMR crisis include improving clinical practices under antibiotic stewardship and repurposing FDA-approved drugs. Quantitative modeling of the population dynamics of AMR can inform these strategies by identifying key mechanisms and consequences of resistance development and predicting resistance persistence, with the potential of guiding treatment design. Here we review the current progress of using mechanistic and machine learning (ML) models to understand and predict the population dynamics of AMR in microbial communities. We highlight the current challenges in mechanistic model construction, explore how ML can overcome these limitations, and discuss the translational potential of the computational models.

抗微生物药物耐药性（AMR）感染已成为全球公共卫生负担。由于对新抗生素的耐药性迅速出现，经济回报有限，以及监管障碍，新抗生素的发现渠道正在枯竭。目前对抗抗生素耐药性危机的策略包括改善抗生素管理下的临床实践和重新利用fda批准的药物。AMR种群动态的定量建模可以通过确定耐药性发展的关键机制和后果以及预测耐药性持久性来为这些策略提供信息，并具有指导治疗设计的潜力。本文综述了利用机制和机器学习（ML）模型来理解和预测微生物群落中AMR的种群动态的最新进展。我们强调了目前在机械模型构建方面的挑战，探讨了机器学习如何克服这些限制，并讨论了计算模型的转化潜力。

引用次数: 0

Applications of DNA-based nanostructures in immunotherapy dna纳米结构在免疫治疗中的应用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-30 DOI: 10.1016/j.addr.2025.115660

Dandan Li , Huarui Liu , Xintong Li , Changping Yang , Hanyin Zhu , Hong Wang , Jianbing Liu , Baoquan Ding

DNA, as a carrier of genetic information, has further been efficiently utilized as a foundational element in creating diverse nanostructures of different shapes and sizes through precise base pairing. With spatial addressability, structural programmability, and remarkable biocompatibility, self-assembled DNA-based nanostructures have been broadly applied in various biomedical research areas, such as bio-imaging, disease diagnosis, and drug delivery. Of particular note, immunotherapy, known for its outstanding therapeutic efficacy, has garnered much attention. In this review, we highlight the recent applications of DNA-based nanostructures (including DNA junction, DNA polyhedron, DNA origami, RCA-based DNA structure, DNA hydrogel, and spherical nucleic acid) in immunotherapy (based on the delivery of CpG adjuvant, tumor antigen, PD1 inhibitor, mRNA vaccine, virus antigen, or direct regulating immune cells). Furthermore, the challenges and future prospects of DNA-based nanostructures for in vivo immunotherapy are discussed.

DNA作为遗传信息的载体，通过精确的碱基配对，进一步有效地利用DNA作为基础元素，创造出不同形状和大小的纳米结构。基于dna的自组装纳米结构具有空间可寻址性、结构可编程性和显著的生物相容性，已广泛应用于生物成像、疾病诊断和药物传递等生物医学研究领域。尤其值得注意的是，以其突出的治疗效果而闻名的免疫疗法引起了人们的广泛关注。在这篇综述中，我们重点介绍了基于DNA的纳米结构（包括DNA连接、DNA多面体、DNA折纸、基于rca的DNA结构、DNA水凝胶和球形核酸）在免疫治疗中的最新应用（基于递送CpG佐剂、肿瘤抗原、PD1抑制剂、mRNA疫苗、病毒抗原或直接调节免疫细胞）。此外，还讨论了基于dna的纳米结构在体内免疫治疗中的挑战和未来前景。

引用次数: 0

Carbon dots as multi-modal contrast agents: opportunities and open challenges for in vivo bioimaging 碳点作为多模态造影剂：体内生物成像的机遇和挑战

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-23 DOI: 10.1016/j.addr.2025.115659

Elisa Sturabotti , Beatriz Sierra-Serrano , Samantha Marcelino Apresto , Michele Cesco , Luca Comparini , Lucia Cardo , Maurizio Prato

Carbon dots (CDs), a class of carbonaceous and fluorescent nanomaterials with ultra-small dimensions (below 10 nm), have become popular nanoparticles in several fields, such as nanomedicine, catalysis, sensing or electronics. Due to their chemical versatility, luminescence, surface functional groups, biocompatibility and water solubility, they have been extensively studied in biomedical field. In this review, we focused on CDs used as nano contrast agents (nCAs) for fluorescence, magnetic resonance or computed tomography imaging in small animal models. We described the advantages of using CDs, highlighting some relevant examples, as well as the current issues that slow down their effective use in biomedicine, such as the rational synthetic design, scant purification and poor characterization. Lastly, we gathered some perspectives to develop carbon dots with more reliable properties and accomplish cutting-edge applications.

碳点（CDs）是一类具有超小尺寸（小于10 nm）的碳质荧光纳米材料，已成为纳米医学、催化、传感或电子等多个领域的热门纳米颗粒。由于其化学通用性、发光性、表面官能团、生物相容性和水溶性等特点，在生物医学领域得到了广泛的研究。在这篇综述中，我们重点介绍了CDs作为纳米造影剂（nCAs）在小动物模型中的荧光、磁共振或计算机断层扫描成像。我们描述了使用cd的优点，重点介绍了一些相关的例子，以及目前阻碍其在生物医学上有效应用的问题，如合成设计不合理、纯化不足和表征不佳。最后，我们收集了一些开发性能更可靠的碳点和实现前沿应用的观点。

引用次数: 0

Advances in carbon nanomaterials and their polymeric composites in neural tissue engineering 碳纳米材料及其聚合物复合材料在神经组织工程中的研究进展

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-22 DOI: 10.1016/j.addr.2025.115658

Baishali Kanjilal , Prince David Okoro , Razieh Jaberi , Ashley Taepakdee , Nourouddin Sharifi , Joshua Morgan , Vijayalakshmi Santhakumar , Victor G. Rodgers , Arameh Masoumi , Iman Noshadi

Carbon‐based nanomaterials (CBMs) and their polymeric composites have garnered widespread interest in treating neurotrauma and neurodegenerative diseases, where restoring damaged central and peripheral nervous systems remains a persistent clinical challenge. These materials provide exceptional electrical conductivity, mechanical robustness, and tunable nanoscale architectures conducive to guiding neuronal growth, synaptic connectivity, and targeted biomolecule delivery. In this review, we explore the rationale, recent advances, and translational potential of CBM scaffolds in promoting neuronal survival, neurite outgrowth, and functional maturity across various experimental models. We detail key fabrication strategies, including electrospinning, phase inversion, 3D bioprinting, and pyrolysis that enable precise control over scaffolds’ structural and mechanical properties while facilitating the incorporation of neurotrophic factors, genes, and therapeutic drugs. Emerging in vivo findings suggest that CBM nanocomposites promote regenerative outcomes in peripheral nerve injuries at levels comparable to, or exceeding conventional autografts, underscoring their promise as off‐the‐shelf solutions. Nonetheless, concerns persist regarding large-scale manufacturing, cytotoxicity, and meeting regulatory standards for clinical use. By highlighting cutting-edge innovations and remaining bottlenecks, this review aims to guide future research endeavors in harnessing CBM scaffolds for safe and effective neural tissue repair.

碳基纳米材料（CBMs）及其聚合物复合材料在治疗神经创伤和神经退行性疾病方面引起了广泛的兴趣，其中修复受损的中枢和周围神经系统仍然是一个持续的临床挑战。这些材料具有优异的导电性、机械稳健性和可调的纳米结构，有助于指导神经元生长、突触连接和靶向生物分子传递。在这篇综述中，我们探讨了CBM支架在各种实验模型中促进神经元存活、神经突生长和功能成熟的基本原理、最新进展和转化潜力。我们详细介绍了关键的制造策略，包括静电纺丝、相转化、3D生物打印和热解，这些策略可以精确控制支架的结构和机械性能，同时促进神经营养因子、基因和治疗药物的结合。新出现的体内研究结果表明，CBM纳米复合材料促进周围神经损伤的再生结果的水平与传统的自体移植物相当，甚至超过传统的自体移植物，强调了它们作为现成解决方案的前景。尽管如此，对大规模生产、细胞毒性和临床使用是否符合监管标准的担忧仍然存在。本文通过对目前研究的前沿创新和存在的瓶颈进行综述，旨在指导未来利用CBM支架进行安全有效的神经组织修复的研究

{"title":"Advances in carbon nanomaterials and their polymeric composites in neural tissue engineering","authors":"Baishali Kanjilal , Prince David Okoro , Razieh Jaberi , Ashley Taepakdee , Nourouddin Sharifi , Joshua Morgan , Vijayalakshmi Santhakumar , Victor G. Rodgers , Arameh Masoumi , Iman Noshadi","doi":"10.1016/j.addr.2025.115658","DOIUrl":"10.1016/j.addr.2025.115658","url":null,"abstract":"<div><div>Carbon‐based nanomaterials (CBMs) and their polymeric composites have garnered widespread interest in treating neurotrauma and neurodegenerative diseases, where restoring damaged central and peripheral nervous systems remains a persistent clinical challenge. These materials provide exceptional electrical conductivity, mechanical robustness, and tunable nanoscale architectures conducive to guiding neuronal growth, synaptic connectivity, and targeted biomolecule delivery. In this review, we explore the rationale, recent advances, and translational potential of CBM scaffolds in promoting neuronal survival, neurite outgrowth, and functional maturity across various experimental models. We detail key fabrication strategies, including electrospinning, phase inversion, 3D bioprinting, and pyrolysis that enable precise control over scaffolds’ structural and mechanical properties while facilitating the incorporation of neurotrophic factors, genes, and therapeutic drugs. Emerging <em>in vivo</em> findings suggest that CBM nanocomposites promote regenerative outcomes in peripheral nerve injuries at levels comparable to, or exceeding conventional autografts, underscoring their promise as off‐the‐shelf solutions. Nonetheless, concerns persist regarding large-scale manufacturing, cytotoxicity, and meeting regulatory standards for clinical use. By highlighting cutting-edge innovations and remaining bottlenecks, this review aims to guide future research endeavors in harnessing CBM scaffolds for safe and effective neural tissue repair.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115658"},"PeriodicalIF":17.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Convection-enhanced delivery for brain malignancies: Technical parameters, formulation strategies and clinical perspectives 脑恶性肿瘤的对流增强输送：技术参数，配方策略和临床前景

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-20 DOI: 10.1016/j.addr.2025.115657

Sara Jamshidi Parvar , Cheng In Wong , Andrew Lewis , Elwira Szychot , Christopher J. Morris , David Shorthouse , Karolina Dziemidowicz

The blood–brain barrier’s protective nature greatly restricts the entrance of active pharmaceutical ingredients (APIs), presenting a significant challenge for effective drug delivery into the brain. Convection-enhanced delivery (CED) is emerging as a promising strategy to overcome this barrier by enabling the direct infusion of APIs at therapeutic concentrations into brain tissue, thereby expanding potential treatment options for brain tumours and neurological conditions. This review provides a current and comprehensive update on the field of CED, highlighting recent advances and ongoing challenges. In addition, various formulation strategies, including nanoparticles, cyclodextrins, and hydrogels, are considered, with an emphasis on identifying optimal formulation properties required to enhance CED administration. With insights from clinical trials, device engineering and pharmaceutical perspectives, this review highlights the critical factors that influence the success of CED and outlines future directions for its effective clinical translation.

血脑屏障的保护性极大地限制了活性药物成分（api）的进入，对药物有效进入大脑提出了重大挑战。对流增强给药（CED）正成为克服这一障碍的一种有前景的策略，它使原料药以治疗浓度直接输注到脑组织中，从而扩大了脑肿瘤和神经系统疾病的潜在治疗选择。本综述提供了CED领域的当前和全面的最新情况，突出了最近的进展和当前的挑战。此外，还考虑了各种配方策略，包括纳米颗粒、环糊精和水凝胶，重点是确定提高CED给药所需的最佳配方特性。本文从临床试验、设备工程和制药的角度分析了影响CED成功的关键因素，并概述了其有效临床转化的未来方向。

{"title":"Convection-enhanced delivery for brain malignancies: Technical parameters, formulation strategies and clinical perspectives","authors":"Sara Jamshidi Parvar , Cheng In Wong , Andrew Lewis , Elwira Szychot , Christopher J. Morris , David Shorthouse , Karolina Dziemidowicz","doi":"10.1016/j.addr.2025.115657","DOIUrl":"10.1016/j.addr.2025.115657","url":null,"abstract":"<div><div>The blood–brain barrier’s protective nature greatly restricts the entrance of active pharmaceutical ingredients (APIs), presenting a significant challenge for effective drug delivery into the brain. Convection-enhanced delivery (CED) is emerging as a promising strategy to overcome this barrier by enabling the direct infusion of APIs at therapeutic concentrations into brain tissue, thereby expanding potential treatment options for brain tumours and neurological conditions. This review provides a current and comprehensive update on the field of CED, highlighting recent advances and ongoing challenges. In addition, various formulation strategies, including nanoparticles, cyclodextrins, and hydrogels, are considered, with an emphasis on identifying optimal formulation properties required to enhance CED administration. With insights from clinical trials, device engineering and pharmaceutical perspectives, this review highlights the critical factors that influence the success of CED and outlines future directions for its effective clinical translation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115657"},"PeriodicalIF":15.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3D printing-enabled spatial patterning of biomimetic signals for bone tissue engineering 用于骨组织工程的仿生信号的3D打印空间模式

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-17 DOI: 10.1016/j.addr.2025.115656

Konstantinos Loukelis , Udayabhanu Jammalamadaka , Antonios G. Mikos

Over the years, sustained research into the role of biomolecules in bone regeneration has provided valuable insights into their potential as therapeutic agents for tissue growth. However, challenges such as short half-lives and high production costs underscore the need for advanced tissue engineering platforms. Precise spatial delivery of these biomolecules to target sites remains a critical requirement. 3D printing has emerged as a powerful technology, enabling the layer-by-layer fabrication of hierarchically complex 3D structures with tailored biomechanical properties. Additionally, it facilitates the preservation and delivery of bioactive molecules following desirable kinetic patterns. This review highlights the most recent and notable advancements of 3D printing-enabled spatial patterning of biological cues aimed at promoting the formation of bone tissue, vascularized bone, osteochondral tissue, and bone-tendon interface.

多年来，对生物分子在骨再生中的作用的持续研究为其作为组织生长治疗剂的潜力提供了有价值的见解。然而，半衰期短、生产成本高等挑战凸显了对先进组织工程平台的需求。这些生物分子精确的空间递送到靶点仍然是一个关键的要求。3D打印已经成为一项强大的技术，能够逐层制造具有定制生物力学特性的分层复杂3D结构。此外，它促进了生物活性分子的保存和传递，遵循理想的动力学模式。本文重点介绍了3D打印技术在促进骨组织、血管化骨、骨软骨组织和骨-肌腱界面形成方面的最新进展。

引用次数: 0

Caenorhabditis elegans as an emerging high throughput chronotherapeutic drug screening platform for human neurodegenerative disorders 秀丽隐杆线虫作为一个新兴的高通量时间治疗药物筛选平台，用于人类神经退行性疾病

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-07-17 DOI: 10.1016/j.addr.2025.115655

Mrutyunjaya Panda , Maria Fakitsa , Maria Markaki , Nektarios Tavernarakis

An increase in the aging population is accompanied by increased susceptibility to age-associated neurodegeneration, with currently no cure. Despite the diversity of symptoms and etiologies, neurodegenerative disorders share mechanistic commonalities and many pathophysiological features. These include disruptions in circadian rhythms that affect neuronal physiology. Systematic investigations in several animal models have advanced our understanding of the molecular processes that link circadian rhythms and neurodegenerative disease states. These models have also been used to screen and validate promising chronotherapeutic drug candidates that target the circadian clock to ameliorate neurodegeneration. With the emergence of robust and reliable methodologies to measure daily rhythms, the nematode model Caenorhabditis elegans has become a versatile tool for high throughput chronotherapeutic drug screening against neurodegenerative disorders. In this review, we discuss the unique features and advantages of C. elegans as an enabling platform for chronotherapeutic drug discovery, towards the development of innovative strategies for the treatment of human neurodegenerative conditions.

老龄化人口的增加伴随着对年龄相关神经变性的易感性增加，目前尚无治愈方法。尽管症状和病因多样，但神经退行性疾病具有机制共性和许多病理生理特征。其中包括影响神经生理的昼夜节律紊乱。在几种动物模型中进行的系统研究提高了我们对昼夜节律和神经退行性疾病状态之间的分子过程的理解。这些模型也被用于筛选和验证有希望的时间治疗候选药物，这些药物以生物钟为靶点来改善神经变性。随着测量日常节律的稳健可靠方法的出现，秀丽隐杆线虫模型已成为针对神经退行性疾病的高通量时间治疗药物筛选的多功能工具。在这篇综述中，我们讨论了秀丽隐杆线虫作为时间治疗药物发现的有利平台的独特特征和优势，从而开发出治疗人类神经退行性疾病的创新策略。

{"title":"Caenorhabditis elegans as an emerging high throughput chronotherapeutic drug screening platform for human neurodegenerative disorders","authors":"Mrutyunjaya Panda , Maria Fakitsa , Maria Markaki , Nektarios Tavernarakis","doi":"10.1016/j.addr.2025.115655","DOIUrl":"10.1016/j.addr.2025.115655","url":null,"abstract":"<div><div>An increase in the aging population is accompanied by increased susceptibility to age-associated neurodegeneration, with currently no cure. Despite the diversity of symptoms and etiologies, neurodegenerative disorders share mechanistic commonalities and many pathophysiological features. These include disruptions in circadian rhythms that affect neuronal physiology. Systematic investigations in several animal models have advanced our understanding of the molecular processes that link circadian rhythms and neurodegenerative disease states. These models have also been used to screen and validate promising chronotherapeutic drug candidates that target the circadian clock to ameliorate neurodegeneration. With the emergence of robust and reliable methodologies to measure daily rhythms, the nematode model <em>Caenorhabditis elegans</em> has become a versatile tool for high throughput chronotherapeutic drug screening against neurodegenerative disorders. In this review, we discuss the unique features and advantages of <em>C. elegans</em> as an enabling platform for chronotherapeutic drug discovery, towards the development of innovative strategies for the treatment of human neurodegenerative conditions.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115655"},"PeriodicalIF":15.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0