Journal of Controlled Release最新文献_第10页

Engineering natural killer cell-derived extracellular vesicles for disease therapy 工程自然杀伤细胞衍生的细胞外囊泡用于疾病治疗

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114535

Wenting Zhang , Xinyang Zhang , Zheyong Zhou , Xiao Lu , Tianci Cheng , Xu Zhang , Wenrong Xu , Zhimin Tao , Hui Qian , Yinghong Shi

As pivotal effector cells of the innate immune system, natural killer (NK) cells play indispensable roles in tumor immunosurveillance and the regulation of various chronic diseases. Despite their therapeutic potential, adoptive NK cell therapies are hindered by limited in vivo persistence and suboptimal tumor infiltration, thereby substantially restricting their clinical efficacy. Recently, NK cell-derived extracellular vesicles (NK-EVs) have attracted considerable attention as a cell-free strategy. They inherit the cytotoxic components of parental NK cells while possessing high biocompatibility, excellent stability, and significant tumor-penetrating capacity. NK-EVs have been shown to exert anticancer, immunoregulatory, anti-inflammatory, and anti-infective functions, contributing to therapeutic effects in both cancers and certain non-neoplastic diseases. As NK-EVs mirror the metabolic state of their parent cells and circulate systemically, they hold considerable promise as diagnostic biomarkers. Furthermore, NK-EVs can be engineered or modified to optimize their applications, notably in cancer therapy. This review provides a comprehensive overview of recent advances in NK-EVs, focusing on their therapeutic effects in cancer and non-neoplastic diseases, their role as biomarkers, and the development of engineered NK-EVs for cancer therapy, while also discussing key challenges and future perspectives for clinical translation.

自然杀伤细胞（natural killer， NK）作为先天免疫系统的关键效应细胞，在肿瘤免疫监视和各种慢性疾病的调控中发挥着不可或缺的作用。尽管具有治疗潜力，但过继NK细胞治疗受到体内持久性有限和肿瘤浸润不理想的阻碍，从而大大限制了其临床疗效。近年来，NK细胞衍生的细胞外囊泡（NK- ev）作为一种无细胞策略引起了人们的广泛关注。它们继承了亲本NK细胞的细胞毒性成分，同时具有高的生物相容性、优异的稳定性和显著的肿瘤穿透能力。nk - ev已被证明具有抗癌、免疫调节、抗炎和抗感染功能，对癌症和某些非肿瘤性疾病都有治疗作用。由于nk - ev反映其亲本细胞的代谢状态并进行系统循环，因此它们作为诊断性生物标志物具有相当大的前景。此外，可以对nk - ev进行工程化或修饰，以优化其应用，特别是在癌症治疗方面。本文综述了nk - ev的最新进展，重点介绍了它们在癌症和非肿瘤疾病中的治疗作用，它们作为生物标志物的作用，以及用于癌症治疗的工程化nk - ev的发展，同时也讨论了临床转化的关键挑战和未来前景。

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引用次数: 0

Dissolving microneedle co-deliver mitochondria-targeted Nanozyme and Tofacitinib for synergistic treatment of Rosacea 溶解微针共递送线粒体靶向纳米酶和托法替尼协同治疗酒渣鼻

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114533

Yuanyan Huang , Wei Lu , Jiahao Hu , Jialu Lang , Qi Zhu , Jiawen Zhu , Xiaohua Tao , Yongzhong Du

Rosacea is a chronic inflammatory skin disease driven by oxidative stress and inflammation, yet it lacks effective treatments that simultaneously combine antioxidant and anti-inflammatory activities. This scarcity underscores the need for innovative therapeutic strategies. Here, we developed an integrated platform by combining a mitochondria-targeted cerium oxide nanozyme (WTCeNPs) and the JAK inhibitor tofacitinib citrate (Tof) within a dissolving microneedle (MN) system. This formulation is designed to overcome challenges in transdermal delivery and minimize systemic side effects, achieving mitochondrial specificity and efficient skin penetration for enhanced therapeutic efficacy. The synthesized WTCeNPs demonstrated excellent biocompatibility, dual SOD- and CAT-like activities, and mitochondrial-targeting capabilities, enabling the efficient scavenging of reactive oxygen species (ROS). The dissolving microneedles co-loaded with Tof and WTCeNPs (Tof/WTCeNPs-MN) possessed robust mechanical properties, successfully penetrating the stratum corneum and achieving complete drug release within 9 min. In vitro, treatment of LL-37- and H₂O₂ -induced HaCaT cell models with Tof/WTCeNPs-MN effectively restored intracellular ROS and inflammatory cytokine expression to physiological levels. Furthermore, in vivo studies on an LL-37-induced rosacea model demonstrated that Tof/WTCeNPs-MN significantly ameliorated disease symptoms. Collectively, these findings establish the Tof/WTCeNPs-MN system as a promising, multifunctional therapeutic platform for rosacea.

酒渣鼻是一种由氧化应激和炎症引起的慢性炎症性皮肤病，但缺乏同时结合抗氧化和抗炎活性的有效治疗方法。这种稀缺性强调了创新治疗策略的必要性。在这里，我们开发了一个集成平台，将线粒体靶向氧化铈纳米酶（WTCeNPs）和JAK抑制剂柠檬酸托法替尼（tofacitinib citrate, Tof）结合在一个溶解微针（MN）系统中。该配方旨在克服经皮给药的挑战，最大限度地减少全身副作用，实现线粒体特异性和有效的皮肤渗透，以提高治疗效果。合成的WTCeNPs具有良好的生物相容性，双SOD和cat样活性，以及线粒体靶向能力，能够有效清除活性氧（ROS）。共载Tof和WTCeNPs的溶解微针（Tof/WTCeNPs- mn）具有良好的力学性能，可成功穿透角质层，并在9 min内完全释放药物。在体外，用Tof/WTCeNPs-MN处理LL-37-和H2O2诱导的HaCaT细胞模型可以有效地将细胞内ROS和炎症细胞因子的表达恢复到生理水平。此外，在ll -37诱导的酒渣鼻模型的体内研究表明，Tof/WTCeNPs-MN可显著改善疾病症状。总的来说，这些发现建立了Tof/WTCeNPs-MN系统作为一个有前途的多功能治疗平台的酒渣鼻。

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引用次数: 0

NQO1-responsive Trimethyl lock benzoquinone: A cleavable linker strategy for antibody-drug conjugates nqo1反应性三甲基锁苯醌：抗体-药物偶联物的可切割连接策略

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114534

Zihao Wang , Kai Liu , Chao Shang , Xiangyu Yan , Yuchao Dong , Dapeng Li , Yiquan Li , Cuiling Zhang , Wei Ren , Chengyuan Ma , Huan Wang , Xiao Li , Shiyong Fan , Wu Zhong

Antibody-drug conjugate (ADC) efficacy is hindered by premature systemic payload release and insufficient tumor activation. Here, an NQO1-responsive linker utilizing trimethyl lock benzoquinone is developed to create NRTL-24, a glioma-targeting ADC. In vitro studies showed NRTL-24 maintained plasma stability while achieving NQO1-dependent MMAE release. It demonstrated potent cytotoxicity in EGFR/NQO1-high glioma cells (U251 IC₅₀ = 0.03 nM; T98G IC₅₀ = 0.06 nM), comparable to free MMAE (U251 IC₅₀ = 0.01 nM; T98G IC₅₀ = 0.02 nM). Notably, toxicity dropped significantly in EGFR/NQO1-low normal cells (HMC3 IC₅₀ = 0.58 mM), yielding >10,000 selectivity index. In vivo, NRTL-24 demonstrated superior tumor-targeting ability, significantly prolonging median survival compared to untreated and temozolomide-treated groups while maintaining favorable safety. This NQO1-responsive linker technology enables precise payload activation in tumor while minimizing off-target effects, establishing NRTL-24 as a promising therapeutic candidate. The strategy provides a blueprint for enzyme-targeted ADC development through tumor- selective linker design.

抗体-药物偶联（ADC）的有效性受到过早的全身有效载荷释放和肿瘤激活不足的阻碍。本研究利用三甲基锁苯醌开发了一种nq01响应连接物，以创建NRTL-24，一种靶向胶质瘤的ADC。体外研究表明NRTL-24在实现nqo1依赖性MMAE释放的同时保持血浆稳定性。它展示了强大的细胞毒性表皮生长因子受体/ NQO1-high神经胶质瘤细胞(U251 IC50 = 0.03  nM; T98G IC50 = 0.06 海里),相当于免费MMAE (U251 IC50 = 0.01  nM; T98G IC50 = 0.02 海里)。值得注意的是，在EGFR/ nqo1低的正常细胞中，毒性显著下降（HMC3 IC50 = 0.58 mM），产生>； 10000选择性指数。在体内，NRTL-24表现出优越的肿瘤靶向能力，与未治疗组和替莫唑胺治疗组相比，显著延长了中位生存期，同时保持了良好的安全性。这种nq01响应连接技术能够在肿瘤中精确激活有效载荷，同时最大限度地减少脱靶效应，使NRTL-24成为有前途的治疗候选药物。该策略通过肿瘤选择性连接体设计为酶靶向ADC的发展提供了蓝图。

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引用次数: 0

Phosphatase and tensin homolog mRNA complexed with hyaluronated lipid nanoparticles for transdermal cancer immunotherapy 磷酸酶和紧张素同源mRNA与透明质脂纳米颗粒复合物用于透皮癌免疫治疗

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114518

Mungu Kim, Zhengyu Piao, Jin Huh, Sei Kwang Hahn

The loss of phosphatase and tensin homolog (PTEN) can lead to resistance to immune checkpoint inhibitors (ICIs) in melanoma, thereby promoting immune evasion and tumor progression. These effects can be reversed by restoring PTEN expression, reactivating antitumor immunity, and enhancing therapeutic responses. Here, we develop a hyaluronate-conjugated lipid nanoparticle (HA-LNP) with HA-dimyristoyl glycerol (DMG) for the non-invasive, transdermal delivery of PTEN mRNA. This amphiphilic lipid enables stable HA integration during LNP self-assembly, effectively replacing PEG, supporting particle stability, biocompatibility, and CD44-mediated targeting. The resulting HA-LNP efficiently encapsulate large mRNA payloads, penetrate the skin, and selectively target CD44-expressing tumor cells. In vitro, PTEN mRNA@HA-LNP restores PTEN expression, induces immunogenic cell death (ICD), and reduces melanoma cell viability. In vivo, topical application results in deep skin and tumor penetration, significantly inhibiting tumor growth and enhancing immune activation with minimal toxicity. Taken together, these results highlight HA-LNP as a promising, clinically translatable platform for localized, mRNA-based cancer immunotherapy.

磷酸酶和紧张素同源物（PTEN）的缺失可导致黑色素瘤对免疫检查点抑制剂（ICIs）产生耐药性，从而促进免疫逃避和肿瘤进展。这些作用可以通过恢复PTEN表达、重新激活抗肿瘤免疫和增强治疗反应来逆转。在这里，我们开发了一种透明质酸偶联脂质纳米颗粒（HA-LNP）和ha -二肉豆蔻酰甘油（DMG），用于PTEN mRNA的非侵入性透皮递送。这种两亲性脂质能够在LNP自组装过程中稳定地整合HA，有效地取代PEG，支持颗粒稳定性、生物相容性和cd44介导的靶向性。由此产生的HA-LNP有效地封装了大量mRNA有效载荷，穿透皮肤，并选择性地靶向表达cd44的肿瘤细胞。在体外，PTEN mRNA@HA-LNP恢复PTEN表达，诱导免疫原性细胞死亡（ICD），并降低黑色素瘤细胞活力。在体内，局部应用导致皮肤深层和肿瘤渗透，显著抑制肿瘤生长和增强免疫激活，毒性最小。综上所述，这些结果突出了HA-LNP作为一个有前途的、临床可翻译的平台，用于局部的、基于mrna的癌症免疫治疗。

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引用次数: 0

Ultrasound-responsive Pickering emulsions enable extracellular matrix disruption for enhanced sonodynamic immunotherapy 超声响应皮克林乳剂使细胞外基质破坏增强声动力免疫治疗

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114537

Xinyu Zhong , Xinghao Zhang , Rui Tang , Wengang Liu , Yuting Cao , Pan Li , Ping Zhou

Sonodynamic therapy (SDT) mediated by aggregation-induced emission (AIE) sonosensitizers markedly enhances reactive oxygen species (ROS) generation by overcoming aggregation-caused quenching. However, the dense extracellular matrix (ECM) in solid tumors restricts sonosensitizer penetration and aggregation, aggravates hypoxia, and dampens immune responses, ultimately limiting SDT efficacy. Developing delivery platforms capable of breaching ECM barriers while relieving ECM-induced hypoxia and immunosuppression is therefore essential for improving AIE-SDT and advancing its clinical translation. Inspired by plant seed explosion–mimetic propagation, we develop an ultrasound-responsive Pickering emulation platform (PEO-CST) that drives deep delivery of AIE-sonosensitizer seeds across the ECM via cavitation effect, while concurrently improving the hypoxic and immunosuppressive tumor microenvironment. Unlike conventional microbubbles, PEO-CST encapsulates oxygen-saturated perfluorocarbon as its core, and the chitosan nanogel shell integrates AIE sonosensitizers and inherently activates the cGAS–STING pathway. This architecture increases AIE-sonosensitizer loading capacity and enables ultrasound-responsive ECM breakthrough of AIE-loaded chitosan nanogel like explosion of seeds. Upon ultrasound excitation, the energy core of PEO-CST disrupts ECM barriers, releases oxygen, and activates the cGAS–STING pathway. The resulting deep penetration and aggregation of AIE sonosensitizers, together with reconstruction of the ECM-mediated hypoxic and immunosuppressive milieu, substantially enhances SDT efficacy. This study presents a multidimensional strategy that overcomes ECM barriers, alleviates tumor hypoxia, and activates immune pathways, offering a path toward clinical implementation of SDT.

由聚集诱导发射（AIE）声敏剂介导的声动力治疗（SDT）通过克服聚集引起的猝灭显著增强活性氧（ROS）的产生。然而，实体瘤中致密的细胞外基质（ECM）限制了声敏剂的渗透和聚集，加重了缺氧，抑制了免疫反应，最终限制了SDT的疗效。因此，开发能够突破ECM屏障的递送平台，同时缓解ECM引起的缺氧和免疫抑制，对于改善ae - sdt和推进其临床转化至关重要。受植物种子模拟爆炸繁殖的启发，我们开发了一种超声响应皮克林仿真平台（PEO-CST），该平台通过空化效应驱动aie -声敏剂种子在ECM中的深度传递，同时改善缺氧和免疫抑制的肿瘤微环境。与传统的微泡不同，PEO-CST以含氧饱和的全氟碳为核心，壳聚糖纳米凝胶壳集成了AIE声敏剂，并固有地激活了cGAS-STING途径。这种结构增加了aie -声敏剂的负载能力，使aie -壳聚糖纳米凝胶的超声响应ECM突破成为可能。在超声激发下，PEO-CST的能量核破坏ECM屏障，释放氧气，激活cGAS-STING通路。由此产生的AIE声敏剂的深度渗透和聚集，以及ecm介导的缺氧和免疫抑制环境的重建，大大增强了SDT的疗效。本研究提出了一种克服ECM障碍、缓解肿瘤缺氧、激活免疫通路的多维策略，为SDT的临床实施提供了途径。

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引用次数: 0

A dual-responsive AI-designed peptide P9-conjugate disrupts E6–E6AP Interface to restore p53 and suppress HPV16-driven cervical cancer 人工智能设计的双响应肽p9偶联物破坏E6-E6AP界面，恢复p53，抑制hpv16驱动的宫颈癌

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-11 DOI: 10.1016/j.jconrel.2025.114536

Yue Hua , Yi Xu , Jiale Wan , Yiqing Fan , Xi Zeng , Hai Qian , Yang Shen

Cervical cancer remains a major global health burden in women, mainly driven by persistent infection with high-risk human papillomavirus (hr-HPV). The viral oncoprotein E6 plays an essential role in HPV-related cervical by promoting p53 degradation via interaction with E6AP. However, blocking the E6-E6AP interaction is difficult due to the lack of clear binding pockets and reliance on flexible protein-protein interactions. In this study, we identify a key sequence in E6AP (S372–382) and improve it through AI-assisted structural analysis to generate an optimized peptide (P9) with high affinity for E6. P9 is further conjugated to chemotherapy drug camptothecin (CPT) to form a dual-responsive compound (Comp.1) with enhanced intracellular delivery, disruption of E6-E6AP interaction, and restoration of p53 function. Our work offers an effective and selective way to interfere with HPV-driven cervical cancer and highlights the potential of structure-guided peptide design in HPV16 E6 protein.

宫颈癌仍然是全球妇女的一个主要健康负担，主要是由高危人乳头瘤病毒（hr-HPV）持续感染引起的。病毒癌蛋白E6通过与E6AP相互作用促进p53降解，在hpv相关宫颈中发挥重要作用。然而，由于缺乏明确的结合口袋和依赖于灵活的蛋白质-蛋白质相互作用，阻断E6-E6AP相互作用是困难的。在这项研究中，我们确定了E6AP的一个关键序列（S372-382），并通过人工智能辅助结构分析对其进行改进，生成了一个与E6高亲和力的优化肽（P9）。P9进一步与化疗药物喜树碱（CPT）偶联，形成双响应化合物（comp1），增强细胞内递送，破坏E6-E6AP相互作用，恢复p53功能。我们的工作提供了一种有效和选择性的方法来干扰hpv驱动的宫颈癌，并强调了结构引导的hpv16e6蛋白肽设计的潜力。

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引用次数: 0

Escherichia coli Nissle 1917 outer membrane vesicles encapsulating oncolytic virus remodel tumor-associated macrophages and kill prostate cancer cells 大肠杆菌Nissle 1917外膜囊泡包裹溶瘤病毒改造肿瘤相关巨噬细胞并杀死前列腺癌细胞

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-10 DOI: 10.1016/j.jconrel.2025.114514

Jian-Xuan Sun , Si-Yang Ma , Jing-Yu Xu , Maimaiti Abudureyimu , Ye An , Jin-Zhou Xu , Si-Han Zhang , Zi-Yi Zhang , Ci-Xiang Guo , Bin-Lei Liu , Shao-Gang Wang , Qi-Dong Xia

Oncolytic virus OH2 exerts cytotoxic effect on prostate tumor cells. However, when administered via vein injection, OH2 struggles to accumulate effectively within tumors, and its therapeutic efficacy is diminished. Bacterial outer membrane vesicles (OMVs), bilayer membrane structures ranging from 20 to 250 nm in size, can serve not only as carriers for targeted drug delivery to tumors but also activate immune responses via pathogen-associated molecular patterns (PAMPs) within them. In this study, we encapsulated OH2 within OMVs derived from Escherichia coli Nissle 1917 (EcN). We aimed to leverage the protective capacity and tumor-targeting properties of EcN-OMVs to enhance OH2 accumulation within tumors. Concurrently, both the EcN-OMVs and OH2 are anticipated to collaboratively remodel the immunosuppressive tumor microenvironment of prostate cancer, thereby enhancing overall immunotherapeutic efficacy.

溶瘤病毒OH2对前列腺肿瘤细胞具有细胞毒作用。然而，当通过静脉注射给药时，OH2难以在肿瘤内有效积累，其治疗效果降低。细菌外膜囊泡（OMVs）是一种双层膜结构，大小在20 - 250 nm之间，不仅可以作为靶向药物递送到肿瘤的载体，还可以通过其内部的病原体相关分子模式（pathogen associated molecular patterns, PAMPs）激活免疫反应。在这项研究中，我们将OH2封装在大肠杆菌Nissle 1917 （EcN）衍生的omv中。我们的目的是利用ecn - omv的保护能力和肿瘤靶向特性来增强肿瘤内的OH2积累。同时，ecn - omv和OH2有望共同重塑前列腺癌的免疫抑制肿瘤微环境，从而提高整体免疫治疗效果。

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引用次数: 0

Machine learning-driven insights into the mechanical performance of polymeric microneedle array patches 机器学习驱动的洞察聚合物微针阵列贴片的机械性能

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-09 DOI: 10.1016/j.jconrel.2025.114505

Xue Yao Liew , Jing Yi Lee , Jia Yee Ong , Ying Ying Tham , Eik Den Yeoh , Mohd Azam Osman , Choon Fu Goh

With growing interest in microneedle technology for enhancing transdermal drug delivery, the current body of literature provides a valuable data reservoir for understanding and predicting mechanical performance — a critical prerequisite for microneedle array patches (MAP) to effectively breach the skin barrier. The integration of artificial intelligence and machine learning (ML) has generated considerable interest in pharmaceutical research, offering the potential to streamline formulation development by reducing experimental workload and time. In this study, ML algorithms were applied to predict the mechanical properties of polymeric MAP using literature-mined data. A total of 313 formulations were extracted from 148 publications, with gradient boosting identified as the most robust model for predicting failure force and in vitro skin insertion, yielding errors of ±0.467 N and ± 7.781 %, respectively. Ex vivo skin penetration data were excluded owing to limited data availability. The models highlighted the predominant influence of microneedle dimensions, particularly inter-needle spacing, needle height and volume, along with polymer content and molecular weight in determining mechanical performance. Overall, this work demonstrates the utility of ML in developing predictive models for mechanical properties of polymeric MAP from existing literature datasets.

随着人们对微针技术增强经皮给药的兴趣日益增加，目前的文献为理解和预测微针阵列贴片（MAP）的机械性能提供了有价值的数据库，这是微针阵列贴片有效突破皮肤屏障的关键先决条件。人工智能和机器学习（ML）的集成引起了人们对药物研究的极大兴趣，通过减少实验工作量和时间，提供了简化配方开发的潜力。在这项研究中，机器学习算法被应用于利用文献挖掘数据预测聚合物MAP的力学性能。从148份出版物中共提取了313个配方，其中梯度增强被认为是预测失效力和体外皮肤插入的最稳健模型，误差分别为±0.467 N和 ± 7.781 %。由于数据可用性有限，排除了体外皮肤穿透数据。这些模型强调了微针尺寸的主要影响，特别是针间距、针高和体积，以及聚合物含量和分子量在决定机械性能方面的影响。总的来说，这项工作证明了机器学习在从现有文献数据集开发聚合物MAP力学性能预测模型中的实用性。

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引用次数: 0

Guanidinylated polymers enable safe and efficient dsRNA delivery in plant cells 胍基化聚合物能够在植物细胞中安全有效地传递dsRNA

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-08 DOI: 10.1016/j.jconrel.2025.114517

Sven Vereecken , Ellen Vandenbussche , Kristof De Schutter , Els J.M. Van Damme , Peter Dubruel

The widespread use of chemical pesticides in crop protection poses serious environmental risks and has been associated with adverse effects to human health. RNA interference (RNAi) offers a sustainable alternative by enabling species-selective gene silencing through double stranded RNA (dsRNA). However, the practical application is hindered by the instability of dsRNA in vivo and inefficient cellular internalization. To address these challenges, we synthesized a small library of twelve polymethacrylate-based polymers (PAEMA and PGUMA) varying in molar mass (MM) and degree of substitution (DS). Comprehensive structural characterization by ¹H NMR, FT-IR, and SEC confirmed the tunability of MM and DS. Biophysical assays, including nucleic acid condensation, DLS, and z-potential measurement showed efficient formation of small, positively charged polyplexes at low N/P ratios. Stability studies revealed that polymers with higher MM and DS provided superior protection against enzymatic degradation, UV, and alkaline conditions. Cytotoxicity assays in Arabidopsis and tobacco cell cultures indicated that guanidinylated polymers, particularly those with higher DS, exhibited reduced toxicity profiles. Cellular uptake experiments further showed that high DS polymers enhanced delivery efficiency. Furthermore, gene silencing assays in GFP-expressing plant cells demonstrated that siRNA delivered with high MM and DS polymers induced transient gene silencing, outperforming naked siRNA. These findings highlight the potential of guanidinylated polymethacrylates as effective RNAi delivery vehicles in plants, offering a favorable balance between polyplex stability, biocompatibility, and delivery efficiency.

在作物保护中广泛使用化学农药造成了严重的环境风险，并对人类健康产生了不利影响。RNA干扰（RNAi）通过双链RNA （dsRNA）实现物种选择性基因沉默，提供了一种可持续的替代方案。然而，dsRNA在体内的不稳定性和细胞内化效率低下阻碍了其实际应用。为了解决这些挑战，我们合成了一个小的库，包括12种基于聚甲基丙烯酸酯的聚合物（PAEMA和PGUMA），它们的摩尔质量（MM）和取代度（DS）不同。通过1H NMR、FT-IR、SEC等综合表征，证实了MM和DS的可调性。生物物理分析，包括核酸缩聚、DLS和z电位测量显示，在低氮磷比下，小的、带正电的多聚物能有效形成。稳定性研究表明，具有较高MM和DS的聚合物在酶降解、紫外线和碱性条件下提供了更好的保护。拟南芥和烟草细胞培养的细胞毒性试验表明，胍基化聚合物，特别是具有较高DS的聚合物，毒性谱降低。细胞摄取实验进一步表明，高DS聚合物提高了递送效率。此外，在表达gfp的植物细胞中进行的基因沉默实验表明，用高MM和DS聚合物传递的siRNA诱导了短暂的基因沉默，优于裸siRNA。这些发现突出了胍基化聚甲基丙烯酸酯作为植物中有效的RNAi递送载体的潜力，在多聚物稳定性、生物相容性和递送效率之间提供了良好的平衡。

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引用次数: 0

Corrigendum to ‘Preclinical evaluation of several polymeric micelles identifies Soluplus®-docetaxel as the most effective candidate in multiple glioblastoma models’ [Journal of Controlled Release (2025) 381:113616] “几种聚合物胶束的临床前评估确定Soluplus®-多西他赛是多发性胶质母细胞瘤模型中最有效的候选者”的更正[Journal of control Release (2025) 381:113616]

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2025-12-08 DOI: 10.1016/j.jconrel.2025.114479

Júlia German-Cortés , Raquel Herrero , Natalia Torroglosa , Alexandra Pumarola , Narine Fischer-Albiol , Sofia Campos-Moreno , Sofia Sabaté , Angels Alcina , Sandra Mancilla , Belén García , Monserrat Llaguno-Munive , Zamira V. Díaz-Riascos , Cláudia Martins , Simó Schwartz Jr , Roser Ferrer-Costa , Ibane Abasolo , Pilar Sanchez-Góméz , Bruno Sarmento , Diana Rafael , Fernanda Andrade

引用次数: 0