Journal of Controlled Release最新文献_第5页

Advancing osteosarcoma 3D modeling in vitro for novel tumor microenvironment-targeted therapies development 推进骨肉瘤三维体外建模，开发新型肿瘤微环境靶向疗法。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-08 DOI: 10.1016/j.jconrel.2024.10.068

Sofia Costa , João Rodrigues , Carolina Vieira , Sofia Dias , Juliana Viegas , Flávia Castro , Bruno Sarmento , Catarina Leite Pereira

Osteosarcoma (OS) represents one of the most common primary bone cancers affecting children and young adults. The available treatments have remained unimproved for the past decades, hampered by the poor knowledge of OS etiology/pathophysiology and the lack of innovative, predictive and biologically relevant in vitro models, that can recapitulate the 3D OS tumor microenvironment (TME). Here, we report the development and characterization of an innovative 3D model of OS, composed of OS tumor cells, immune cells (macrophages) and mesenchymal stem cells (MSCs), that formed a multicellular tissue spheroid (MCTS). This fully humanized 3D model was shown to accurately mimic the native histological features of OS, while innately leading to the polarization of macrophages towards an M2-like phenotype, highly aggressive and pro-tumor profile. Upon the exposure to immunomodulatory molecules, the MCTS were shown to be responsive by shifting macrophages polarization, and dramatically altering the TME secretome. In agreement, when treated with immunomodulatory/stimulatory nanoparticles (NPSs), we were able to revert the TME secretome towards an anti-inflammatory profile. This study establishes an advanced 3D OS model capable of shedding light on macrophages and MSCs contributions to disease progression, paving the way for the development of innovative therapeutic approaches targeting the OS TME, while providing a biologically relevant in vitro tool for the efficacy screening of novel OS therapeutic approaches.

骨肉瘤（Osteosarcoma，OS）是儿童和年轻人最常见的原发性骨癌之一。由于对骨肉瘤的病因学/病理生理学知之甚少，以及缺乏可再现三维骨肉瘤肿瘤微环境（TME）的创新性、预测性和生物相关性体外模型，现有的治疗方法在过去几十年中一直没有得到改善。在此，我们报告了由 OS 肿瘤细胞、免疫细胞（巨噬细胞）和间充质干细胞（间充质干细胞）组成的 OS 创新三维模型的开发和特征描述，该模型形成了一个多细胞组织球体（MCTS）。研究表明，这种完全人源化的三维模型能准确模拟 OS 的原生组织学特征，同时导致巨噬细胞向 M2 样表型极化，具有高度侵袭性和促肿瘤特征。在暴露于免疫调节分子后，MCTS 通过改变巨噬细胞的极化和显著改变 TME 分泌组而显示出反应能力。同样，当使用免疫调节/刺激性纳米颗粒（NPSs）治疗时，我们能够将TME分泌组恢复到抗炎状态。这项研究建立了一种先进的三维 OS 模型，能够揭示巨噬细胞和间充质干细胞对疾病进展的影响，为开发针对 OS TME 的创新治疗方法铺平了道路，同时也为新型 OS 治疗方法的疗效筛选提供了一种生物相关的体外工具。

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引用次数: 0

Self-healing adhesive hydrogels for sustained ozone release: Enhanced antibacterial properties and improved wound healing. 可持续释放臭氧的自愈合粘合水凝胶：增强抗菌性能，改善伤口愈合。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-08 DOI: 10.1016/j.jconrel.2024.10.053

Shanbo Ma, Conghui Han, Xi Chen, Long Li, Xushuai Chen, Wei Zhang, Jin Wang, Fu Han, Luke Yan, Xiaopeng Shi

Antibacterial hydrogels have generated significant interest for their potential therapeutic applications. Ozone (O₃) is recognized for its antibacterial, anti-inflammatory, immunomodulatory, and anti-hypoxic properties, along with its minimal residual impact. However, the development of sustained O₃-release antibacterial hydrogels has been challenging due to the low solubility and short lifespan of ozone. We present an ozone-loaded emulsion hydrogel (ozonegel), which encapsulates ozonized oil within a nanoclay-poly(methacryloxyethyl sulfobetaine) supramolecular network. This adhesive, self-healing ozonegel achieves high ozone loading (91.3 mmol/kg) and releases O₃ and reactive oxygen species (ROS) over 36 h. It demonstrates broad antibacterial and anti-inflammatory effects, promoting wound healing. The remarkable properties of ozonegels suggest significant potential for advanced biomedical applications.

抗菌水凝胶因其潜在的治疗用途而备受关注。臭氧（O₃）具有抗菌、消炎、免疫调节和抗缺氧等特性，而且其残留影响极小。然而，由于臭氧的溶解度低、寿命短，开发持续释放 O₃ 的抗菌水凝胶一直面临挑战。我们提出了一种臭氧载荷乳液水凝胶（orozonegel），它将臭氧油包裹在纳米粘土-聚（甲基丙烯酰氧乙基磺基甜菜碱）超分子网络中。这种具有粘合性、自愈合的臭氧凝胶可实现高臭氧负荷（91.3 毫摩尔/千克），并在 36 小时内释放臭氧和活性氧（ROS）。它具有广泛的抗菌和消炎作用，可促进伤口愈合。臭氧凝胶的显著特性表明它在先进生物医学应用方面具有巨大潜力。

引用次数: 0

Cerebral biomimetic nano-drug delivery systems: A frontier strategy for immunotherapy 脑生物仿生纳米给药系统：免疫疗法的前沿策略

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-08 DOI: 10.1016/j.jconrel.2024.10.058

Hao Tian , Jiaxin Yao , Qi Ba , Yuanyuan Meng , Yanan Cui , Liangzhu Quan , Wei Gong , Yuli Wang , Yang Yang , Meiyan Yang , Chunsheng Gao

Brain diseases are a significant threat to human health, especially in the elderly, and this problem is growing as the aging population increases. Efficient brain-targeted drug delivery has been the greatest challenge in treating brain disorders due to the unique immune environment of the brain, including the blood-brain barrier (BBB). Recently, cerebral biomimetic nano-drug delivery systems (CBNDSs) have provided a promising strategy for brain targeting by mimicking natural biological materials. Herein, this review explores the latest understanding of the immune microenvironment of the brain, emphasizing the immune mechanisms of the occurrence and progression of brain disease. Several brain targeting systems are summarized, including cell-based, exosome-based, protein-based, and microbe-based CBNDSs, and their immunological mechanisms are highlighted. Moreover, given the rise of immunotherapy, the latest applications of CBNDSs in immunotherapy are also discussed. This review provides a comprehensive understanding of CBNDSs and serves as a guideline for immunotherapy in treating brain diseases. In addition, it provides inspiration for the future of CBNDSs.

脑部疾病是人类健康的重大威胁，尤其是在老年人中，而且随着老龄化人口的增加，这一问题正在日益严重。由于大脑独特的免疫环境，包括血脑屏障（BBB），高效的脑靶向给药一直是治疗脑部疾病的最大挑战。最近，脑生物仿生纳米给药系统（CBNDS）通过模仿天然生物材料，为脑靶向给药提供了一种前景广阔的策略。本综述探讨了对脑部免疫微环境的最新认识，强调了脑部疾病发生和发展的免疫机制。综述了几种脑靶向系统，包括基于细胞的、基于外泌体的、基于蛋白质的和基于微生物的 CBNDS，并重点介绍了它们的免疫学机制。此外，鉴于免疫疗法的兴起，还讨论了 CBNDS 在免疫疗法中的最新应用。这篇综述提供了对 CBNDS 的全面了解，可作为治疗脑部疾病的免疫疗法指南。此外，它还为 CBNDS 的未来发展提供了启示。

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引用次数: 0

Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer 多价 DR5 受体集群激动剂与组蛋白去乙酰化酶抑制剂联合治疗结肠癌。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-08 DOI: 10.1016/j.jconrel.2024.10.062

Jiahui Li , Jaden Arnold , Monika Sima , Hasan Al Faruque , Jacob Galang , Sophia Hu-Lieskovan , Jindřich Kopeček , Jiyuan Yang

Death Receptor 5 (DR5) targeted therapies offer significant promise due to their pivotal role in mediating the extrinsic pathway of apoptosis. Despite DR5 overexpression in various malignancies and the potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), clinical applications of anti-DR5 monoclonal antibodies (mAbs) have been hampered by suboptimal outcomes potentially due to lack of receptor clustering.

To address the limitation, we developed N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based conjugates integrating multiple copies of DR5-targeting peptide (cyclic WDCLDNRIGRRQCVKL; cDR5) to enhance receptor clustering and apoptosis. Three conjugates with variable number of cDR5 were prepared and denoted as P_H-cDR5 (high valence), P_M-cDR5 (medium valence) and P_L-cDR5 (low valence). Our studies in TRAIL-sensitive and resistant cancer cell lines demonstrated that the HPMA copolymer-peptide conjugates (P-cDR5) significantly improved DR5 receptor clustering and induced apoptosis effectively. In TRAIL-sensitive colon cancer cells (COLO205, HCT-116), P-cDR5 showed efficacy comparable to anti-DR5 mAb Drozitumab (DRO), but P-cDR5 outperformed DRO in TRAIL-resistant cells (HT-29), highlighting the importance of efficient receptor clustering. In COLO205 cells P_M-cDR5 exhibited an IC50 of 94 pM, while P_H-cDR5 had an even lower IC50 of 15 pM (based on cDR5 equivalent concentration), indicating enhanced potency of the multivalent HPMA copolymer-based system with a flexible polymer backbone in comparison with the IC₅₀ for TRAIL at 0.12 nM. Combining P-cDR5 with valproic acid, a histone deacetylase inhibitor, resulted in further enhancement of apoptosis inducing efficacy, along with destabilizing mitochondrial membranes and increased sensitivity of TRAIL-resistant cells. These findings suggest that attaching multiple cDR5 peptides to a flexible water-soluble polymer carrier not only overcomes the limitations of previous designs but also offers a promising avenue for treating resistant cancers, pointing toward the need for further preclinical exploration and validation of this innovative strategy.

死亡受体5（DR5）靶向疗法在介导细胞凋亡的外在途径中发挥着关键作用，因此前景广阔。尽管DR5在各种恶性肿瘤中过度表达，而且肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）也具有潜力，但抗DR5单克隆抗体（mAbs）的临床应用却受到了阻碍，原因可能是缺乏受体集群，导致疗效不理想。为了解决这一局限性，我们开发了基于 N-（2-羟基丙基）甲基丙烯酰胺（HPMA）共聚物的共轭物，其中整合了多份 DR5 靶向肽（环 WDCLDNRIGRRQCVKL；cDR5），以增强受体集群和细胞凋亡。我们制备了三种具有不同数量 cDR5 的共轭物，分别称为 PH-cDR5（高价）、PM-cDR5（中价）和 PL-cDR5（低价）。我们在对 TRAIL 敏感和耐药的癌细胞系中进行的研究表明，HPMA 共聚物-多肽共轭物（P-cDR5）能显著改善 DR5 受体的聚集，并有效诱导细胞凋亡。在对 TRAIL 敏感的结肠癌细胞（COLO205、HCT-116）中，P-cDR5 的疗效与抗 DR5 mAb 屈珠单抗（DRO）相当，但在对 TRAIL 抗性的细胞（HT-29）中，P-cDR5 的疗效优于 DRO，这凸显了有效受体聚类的重要性。在 COLO205 细胞中，PM-cDR5 的 IC50 为 94 pM，而 PH-cDR5 的 IC50 甚至更低，仅为 15 pM（基于 cDR5 的等效浓度），这表明与 TRAIL 的 IC50 0.12 nM 相比，基于多价 HPMA 共聚物的柔性聚合物骨架系统的效力更强。将 P-cDR5 与组蛋白去乙酰化酶抑制剂丙戊酸结合使用，可进一步增强诱导细胞凋亡的功效，同时还能破坏线粒体膜的稳定性，并提高 TRAIL 抗性细胞的敏感性。这些研究结果表明，将多个 cDR5 肽连接到柔性水溶性聚合物载体上不仅克服了以往设计的局限性，还为治疗耐药性癌症提供了一条前景广阔的途径，这表明有必要对这一创新策略进行进一步的临床前探索和验证。

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引用次数: 0

Leveraging machine learning to streamline the development of liposomal drug delivery systems 利用机器学习简化脂质体给药系统的开发。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-08 DOI: 10.1016/j.jconrel.2024.10.065

Remo Eugster , Markus Orsi , Giorgio Buttitta , Nicola Serafini , Mattia Tiboni , Luca Casettari , Jean-Louis Reymond , Simone Aleandri , Paola Luciani

Drug delivery systems efficiently and safely administer therapeutic agents to specific body sites. Liposomes, spherical vesicles made of phospholipid bilayers, have become a powerful tool in this field, especially with the rise of microfluidic manufacturing during the COVID-19 pandemic. Despite its efficiency, microfluidic liposomal production poses challenges, often requiring laborious, optimization on a case-by-case basis. This is due to a lack of comprehensive understanding and robust methodologies, compounded by limited data on microfluidic production with varying lipids. Artificial intelligence offers promise in predicting lipid behaviour during microfluidic production, with the still unexploited potential of streamlining development. Herein we employ machine learning to predict critical quality attributes and process parameters for microfluidic-based liposome production. Validated models predict liposome formation, size, and production parameters, significantly advancing our understanding of lipid behaviour. Extensive model analysis enhanced interpretability and investigated underlying mechanisms, supporting the transition to microfluidic production. Unlocking the potential of machine learning in drug development can accelerate pharmaceutical innovation, making drug delivery systems more adaptable and accessible.

药物输送系统能高效、安全地将治疗药物输送到人体特定部位。脂质体是由磷脂双分子层构成的球形囊泡，已成为这一领域的有力工具，尤其是在 COVID-19 大流行期间，微流控生产技术的兴起更是如此。尽管微流控脂质体生产效率很高，但它也带来了挑战，往往需要逐个进行费力的优化。这是由于缺乏全面的了解和可靠的方法，再加上使用不同脂质进行微流控生产的数据有限。人工智能在预测微流控生产过程中的脂质行为方面大有可为，其简化开发的潜力仍有待开发。在此，我们利用机器学习预测基于微流控生产脂质体的关键质量属性和工艺参数。经过验证的模型可以预测脂质体的形成、大小和生产参数，极大地促进了我们对脂质行为的理解。广泛的模型分析增强了可解释性并研究了潜在机制，为过渡到微流控生产提供了支持。释放机器学习在药物开发中的潜力可以加速制药创新，使药物输送系统更具适应性和可及性。

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引用次数: 0

Reactive oxygen species-responsive polydopamine-PtCuTe nanoparticle-loaded microneedle system for promoting the healing of infected skin wounds 促进感染性皮肤伤口愈合的活性氧反应型多巴胺-铂铜碲纳米粒子微针系统。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-07 DOI: 10.1016/j.jconrel.2024.11.002

Hongfan Che , Junzhi Xu , Dong Wu , Siliang Chen , Chengkang Liu , Chongbao Zhao , Kun Peng

Nanozymes, known for their high efficiency in scavenging reactive oxygen species (ROS), have received significant attention in promoting the healing of infected wounds. Herein, we reported a novel multifunctional PDA-PtCuTe nanozyme with excellent ROS scavenging, antibacterial, pro-angiogenic, anti-inflammatory, and immune regulatory properties. It was loaded onto microneedles (PTPP-MN) for treating infected wounds. In vitro experiments demonstrated its ability to scavenge ROS and exhibit antioxidant properties. Compared to PT-MN (11.03 ± 3.37 %) and PTP-MN (42.30 ± 2.60 %), the ROS scavenging rate of PTPP-MN reached 63.63 ± 4.42 %. The microneedle exhibits good biocompatibility, stimulating fibroblast migration, endothelial angiogenesis, and M2 macrophage polarization. Additionally, it effectively eliminates ROS and provides antioxidant effects while inhibiting the viability of S. aureus and E. coli. Animal experiments showed that the PTPP-MN group achieved near-complete re-epithelialization by the third day compared to other groups. Histological observations revealed that the PTPP-MN group exhibited enhanced granulation tissue formation, epithelial regeneration, and angiogenesis. After PTPP-MN treatment, the local immune response shifted from a pro-inflammatory state to a pro-regenerative state. Our results indicate that PTPP-MN holds great promise for infected wound healing with reduced scar formation.

纳米酶以其高效清除活性氧（ROS）而闻名，在促进感染伤口愈合方面备受关注。在此，我们报告了一种新型多功能 PDA-PtCuTe 纳米酶，它具有出色的清除 ROS、抗菌、促血管生成、抗炎和免疫调节特性。它被载入微针（PTPP-MN），用于治疗感染伤口。体外实验证明了它清除 ROS 和抗氧化的能力。与 PT-MN（11.03 ± 3.37 %）和 PTP-MN（42.30 ± 2.60 %）相比，PTPP-MN 的 ROS 清除率达到了 63.63 ± 4.42 %。微针具有良好的生物相容性，可刺激成纤维细胞迁移、内皮血管生成和 M2 巨噬细胞极化。此外，它还能有效消除 ROS 并提供抗氧化作用，同时抑制金黄色葡萄球菌和大肠杆菌的活力。动物实验表明，与其他组相比，PTPP-MN 组在第三天就实现了几乎完全的再上皮化。组织学观察显示，PTPP-MN 组的肉芽组织形成、上皮再生和血管生成均有所增强。经 PTPP-MN 处理后，局部免疫反应从促炎症状态转变为促再生状态。我们的研究结果表明，PTPP-MN 在感染伤口愈合和减少疤痕形成方面大有可为。

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引用次数: 0

Controlled release of mesenchymal stem cell-derived nanovesicles through glucose- and reactive oxygen species-responsive hydrogels accelerates diabetic wound healing 通过葡萄糖和活性氧响应水凝胶控制间充质干细胞衍生纳米颗粒的释放，加速糖尿病伤口愈合。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-07 DOI: 10.1016/j.jconrel.2024.11.003

Fangzhou Du , Shumang Zhang , Shikai Li , Shaocong Zhou , Dongao Zeng , Jingzhong Zhang , Shuang Yu

Wound healing is often impaired in patients with diabetes. Mesenchymal stem cells (MSCs) and MSCs-derived nanovesicles (MNVs) hold promise as therapeutic agents for managing diabetic wounds. However, efficient delivery and controlled release of MNVs within these wounds are essential for maximizing therapeutic effectiveness. In this study, we developed a dual-responsive hydrogel designed to respond to elevated levels of glucose and reactive oxygen species. This hydrogel combines polyvinyl alcohol with phenylboronic acid-grafted chitosan, referred to as PBA-CP, while MNVs were produced by shearing MSCs through membranes with varying pore sizes. The composite PBA-CP/MNVs hydrogel significantly accelerated wound healing in a diabetic wound model by promoting epithelialization, dermal reconstruction, hair follicle formation, and angiogenesis. MNVs were readily taken up by keratinocytes, fibroblasts, and endothelial cells, stimulating their proliferation and migration. Altogether, the chitosan-based PBA-CP/MNVs composite hydrogel presents a promising therapeutic strategy for diabetic wound treatment.

糖尿病患者的伤口愈合通常会受到影响。间充质干细胞（MSCs）和间充质干细胞衍生的纳米颗粒（MNVs）有望成为治疗糖尿病伤口的药物。然而，要最大限度地提高治疗效果，必须在这些伤口内高效输送和控制 MNVs 的释放。在这项研究中，我们开发了一种双重响应水凝胶，旨在对升高的葡萄糖和活性氧水平做出反应。这种水凝胶结合了聚乙烯醇和苯硼酸接枝壳聚糖（称为 PBA-CP），而 MNV 则是通过剪切具有不同孔径的膜产生的。PBA-CP/MNVs复合水凝胶通过促进上皮化、真皮重建、毛囊形成和血管生成，显著加快了糖尿病伤口模型的伤口愈合。MNV 很容易被角质形成细胞、成纤维细胞和内皮细胞吸收，刺激它们的增殖和迁移。总之，基于壳聚糖的 PBA-CP/MNVs 复合水凝胶为糖尿病伤口治疗提供了一种前景广阔的治疗策略。

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引用次数: 0

Phage-liposome nanoconjugates for orthopedic biofilm eradication 用于消除骨科生物膜的噬菌体-脂质体纳米共轭物。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-06 DOI: 10.1016/j.jconrel.2024.09.049

Lei Wang , Tamta Tkhilaishvili , Zheng Jiang , Rima Fanaei Pirlar , Yu Ning , Adrián Millán Laleona , Jiaxing Wang , Jin Tang , Qiaojie Wang , Andrej Trampuz , Mercedes Gonzalez Moreno , Xianlong Zhang

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.

耐多药（MDR）细菌感染已成为全球公共卫生的最大威胁之一。治疗困难的原因之一是缺乏进入 MDR 细菌生物膜的适当给药策略，因为厚厚的胞外聚合物（EPS）层阻碍了抗生素和纳米粒子的渗透。在此，我们提出了一种新型生物活性纳米脂质体和噬菌体共轭物，用于有针对性地消除骨科感染中的 MDR 生物膜。噬菌体 Sb-1 具有降解 EPS 的能力，它与负载抗生素的脂质体共轭。在遇到生物膜时，噬菌体 Sb-1 会降解 EPS 结构，从而增加细菌对抗生素的敏感性，并使抗生素深入生物膜。因此，本研究通过体外和体内研究证明，使用低剂量抗生素就能有效清除 MDR 细菌生物膜。值得注意的是，在大鼠假体关节感染（PJI）模型中，我们发现脂质体-噬菌体纳米共轭物能有效降低感染区域的细菌负荷，并显著促进骨髓炎的恢复。因此，我们认为噬菌体与脂质体的结合为治疗骨科感染以及其他深部组织感染提供了新的可能性。

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引用次数: 0

Conquering dual challenges: A sialic-modified liposome for targeting activated neutrophils to tackle comorbid lung inflammation and cancer metastasis 征服双重挑战：以活化的中性粒细胞为靶标，解决肺部炎症和癌症转移并发症的硅胶修饰脂质体。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-06 DOI: 10.1016/j.jconrel.2024.10.048

Cong Li , Zhihang Li , Lihong Wang , Kexin Zhang , Zehao Li , Yating Ji , Jing Li , Yifan Zhang , Lijiang Chen

In clinical settings, cancer frequently coexists with multi-system diseases. Owing to compromised immune systems, patients with cancer exhibit an increased susceptibility to infections and inflammation. Notably, lung inflammation occurs with high incidence among these patients. Furthermore, the inflammatory milieu within the lungs often accelerates the metastasis of cancer, thereby enhancing mortality rates and posing substantial challenges for clinical management. To date, effective strategies addressing both lung inflammation and cancer concurrently are lacking. In this context, we introduce a novel therapeutic approach involving a sialic acid-lipid derivative (SA-PG10-C18) modified doxorubicin-curcumin co-loaded liposome (DOX/CUR-SAL). This formulation effectively targeted activated neutrophils, which are abundantly present in inflammatory and metastatic lung tissues. DOX/CUR-SAL notably inhibited neutrophil-mediated pro-inflammatory and pro-metastatic processes. Utilizing a newly established mouse model of acute lung injury (ALI) and metastasis comorbidity, DOX/CUR-SAL modulated the lung immune microenvironment and arrested the progression of both inflammation and metastasis, without inducing side effects. The treated animals demonstrated favorable survival conditions, persisting beyond 45 days. This innovative therapeutic strategy offers a novel concept and reference for treating comorbid conditions of tumors and inflammation, thus breaking the clinical impasse where lung inflammation and cancer metastasis have been treated separately.

在临床上，癌症经常与多系统疾病并存。由于免疫系统受损，癌症患者对感染和炎症的易感性增加。值得注意的是，肺部炎症在这些患者中发病率很高。此外，肺部的炎症环境往往会加速癌症的转移，从而提高死亡率，给临床治疗带来巨大挑战。迄今为止，还缺乏同时应对肺部炎症和癌症的有效策略。在此背景下，我们介绍了一种新的治疗方法，它涉及一种经硅酸-脂质衍生物（SA-PG10-C18）修饰的多柔比星-姜黄素共载脂质体（DOX/CUR-SAL）。这种制剂能有效靶向活化的中性粒细胞，而中性粒细胞大量存在于炎症和转移性肺组织中。DOX/CUR-SAL 能显著抑制中性粒细胞介导的促炎症和促转移过程。利用新建立的急性肺损伤（ALI）和转移合并症小鼠模型，DOX/CUR-SAL 调节了肺部免疫微环境，阻止了炎症和转移的发展，且不会产生副作用。接受治疗的动物显示出良好的存活条件，存活时间超过 45 天。这种创新的治疗策略为治疗肿瘤和炎症并发症提供了新的理念和参考，从而打破了肺部炎症和癌症转移分别治疗的临床僵局。

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引用次数: 0

Microparticle and nanoparticle-based influenza vaccines 基于微粒子和纳米粒子的流感疫苗。

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2024-11-06 DOI: 10.1016/j.jconrel.2024.10.031

Luis Ontiveros-Padilla , Eric M. Bachelder , Kristy M. Ainslie

Influenza infections are a health public problem worldwide every year with the potential to become the next pandemic. Vaccination is the most effective strategy to prevent future influenza outbreaks, however, influenza vaccines need to be reformulated each year to provide protection due to viral antigenic drift and shift. As more efficient influenza vaccines are needed, it is relevant to recapitulate strategies to improve the immunogenicity and broad reactivity of the current vaccines. Here, we review the current approved vaccines in the U.S. market and the platform used for their production. We discuss the different approaches to develop a broadly reactive vaccine as well as reviewing the adjuvant systems that are under study for being potentially included in future influenza vaccine formulations. The main components of the immune system involved in achieving a protective immune response are reviewed and how they participate in the trafficking of particles systemically and in the mucosa. Finally, we describe and classify, according to their physicochemical properties, some of the potential micro and nano-particulate platforms that can be used as delivery systems for parenteral and mucosal vaccinations.

流感感染是每年全球范围内的公共卫生问题，有可能成为下一次大流行病。接种疫苗是预防未来流感爆发的最有效策略，然而，由于病毒抗原的漂移和转变，流感疫苗每年都需要重新配置以提供保护。由于需要更有效的流感疫苗，因此有必要重新研究提高现有疫苗免疫原性和广泛反应性的策略。在此，我们回顾了目前美国市场上获批的疫苗及其生产平台。我们讨论了开发广泛反应性疫苗的不同方法，并回顾了正在研究的可能用于未来流感疫苗配方的佐剂系统。我们还回顾了参与实现保护性免疫反应的免疫系统的主要组成部分，以及它们如何参与颗粒在全身和粘膜中的运输。最后，我们根据微粒和纳米颗粒的理化特性，对一些可用作肠外和粘膜疫苗接种递送系统的潜在微粒和纳米颗粒平台进行了描述和分类。

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引用次数: 0