International Journal of Pharmaceutics: X最新文献_第8页

Improved bioavailability and anti-nephrotoxicity efficacy of polydatin on cisplatin-induced AKI via a dual-targeting fucoidan delivery system 通过双靶向岩藻糖聚糖递送系统提高聚丹素对顺铂诱导AKI的生物利用度和抗肾毒性功效

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-18 DOI: 10.1016/j.ijpx.2025.100422

Yinghan Wang , Shichao Liu , Feikai Zhu , Xuefei Wang , Hanyu Wang , Lin Long , Jun Xiao , Chuanlong Guo

Acute kidney injury (AKI) is a common and serious complication in clinical practice, especially when using chemotherapy drug cisplatin, which severely limits its anti-cancer efficacy. This study developed a novel nano delivery system (Fu-4-PBA/Po NPs) that combines fucoidan (Fu), endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA), and natural antioxidant Polydatin (Po) to simultaneously alleviate cisplatin induced oxidative stress and ERS. The optimized Fu-4-PBA/Po NPs showed an average size of 102 ± 3.46 nm, a zeta potential of −16.5 ± 0.49 mV, and a high drug loading capacity of 10.34 ± 0.6 %. They exhibited excellent stability and a sustained release profile in vitro. In vitro results showed that treatment with Fu-4-PBA/Po NPs led to a marked increase in cell survival by 34.73 ± 3.54 percentage points compared to the model group, which had a survival rate of 45.97 ± 2.76 %. Furthermore, Fu-4-PBA/Po NPs effectively inhibited the accumulation of reactive oxygen species (ROS), mitochondrial membrane potential decline, and calcium ion release by targeting P-selectin and endoplasmic reticulum (ER) at the site of inflammation, and significantly alleviate cisplatin induced cell apoptosis. Mechanism studies showed that nanocomposites alleviate ERS by inhibiting the PERK-eIF2α-ATF4-CHOP pathway, while blocking the activation of the cGAS-STING pathway, thereby reducing DNA damage and inflammatory response. Pharmacokinetic studies showed that the peak concentration (Cmax) of the nanoparticles reached 2.2 times that of free Po, and the area under the curve (AUC) increased by 2 times. In animal studies, administration of Fu-4-PBA/Po NPs at a dose of 100 mg/kg notably ameliorated renal function, as indicated by reductions in serum creatinine (SCr) and blood urea nitrogen (BUN) levels by 84.3 % and 62.4 %, respectively, and also improved kidney histopathology. This study provided a dual targeted nano-delivery strategy for cisplatin induced AKI therapy, which has important clinical application potential.

急性肾损伤（Acute kidney injury， AKI）是临床上常见且严重的并发症，尤其是化疗药物顺铂的使用，严重限制了其抗癌效果。本研究开发了一种新型纳米递送系统Fu-4-PBA/Po NPs，该系统结合岩藻聚糖（Fu）、内质网应激（ERS）抑制剂4-苯基丁酸（4-PBA）和天然抗氧化剂聚datatin (Po)，同时缓解顺铂诱导的氧化应激和ERS。优化后的Fu-4-PBA/Po NPs平均尺寸为102±3.46 nm， zeta电位为−16.5±0.49 mV，载药量为10.34±0.6%。它们在体外表现出良好的稳定性和缓释特性。体外实验结果显示，与模型组相比，Fu-4-PBA/Po NPs可显著提高小鼠细胞存活率34.73±3.54个百分点，其存活率为45.97±2.76%。此外，Fu-4-PBA/Po NPs通过靶向p -选择素和内质网（ER），有效抑制炎症部位活性氧（ROS）的积累、线粒体膜电位下降和钙离子释放，显著减轻顺铂诱导的细胞凋亡。机制研究表明，纳米复合材料通过抑制PERK-eIF2α-ATF4-CHOP通路，同时阻断cGAS-STING通路的激活，从而减轻ERS的损伤和炎症反应。药代动力学研究表明，纳米颗粒的峰值浓度（Cmax）达到游离Po的2.2倍，曲线下面积（AUC）增加了2倍。在动物实验中，100 mg/kg剂量的Fu-4-PBA/Po NPs显著改善了肾功能，血清肌酐（SCr）和血尿素氮（BUN）水平分别降低了84.3%和62.4%，并改善了肾脏组织病理学。本研究为顺铂诱导AKI治疗提供了双靶向纳米递送策略，具有重要的临床应用潜力。

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引用次数: 0

Targeted probiotic tabletting: A hybrid active learning and finite element modelling approach for process optimisation 目标益生菌片剂：混合主动学习和有限元建模方法的过程优化

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-17 DOI: 10.1016/j.ijpx.2025.100420

Bide Wang , Xilu Wang , Oleksiy V. Klymenko , Jiawei Hu , Rachael Gibson , Andrew Middleton , Chuan-Yu Wu

Tablets are an efficient dosage form for delivering probiotics. Prior studies have identified compression pressure, compression speed, and precompression pressure as critical process parameters determining probiotic survival during tabletting. However, due to the labour-intensive and time-consuming nature of experimental investigations, most previous studies focused on evaluating the impact of individual parameters in isolation. Consequently, the rapid and systematic identification of optimal process parameters to maximise probiotic survival remains a significant and unresolved challenge in pharmaceutical formulation research. To address this gap, an integrated approach combining active learning (AL) based Gaussian process regression (GPR) with finite element (FE) modelling was developed to systematically explore the compaction parameter space and identify optimal process conditions. All data utilised in AL were generated using an FE model that was specifically developed to predict viability of probiotics during tabletting. Remarkably, the integrated approach achieved high prediction performance after only 78 iterations, demonstrating a coefficient of determination (R²) of 0.96 across the entire design space for predicting probiotic survival rate during tabletting. Using the well-trained model, a global random sampling strategy combined with threshold filtering was employed to identify regions of the design space likely to yield near-optimal survival rates. Furthermore, the exploration of compression speed and precompression pressure at selected fixed main compression pressures enabled the generation of survival rate maps, providing insights into the interplay between probiotic survival rate and tablet mechanical performance. This study demonstrated the potential of hybrid data-driven and first-principles modelling approaches as a robust strategy for optimising probiotic tabletting processes and accelerating pharmaceutical development.

片剂是提供益生菌的有效剂型。先前的研究已经确定压缩压力、压缩速度和预压缩压力是决定益生菌在压片过程中存活的关键工艺参数。然而，由于实验调查的劳动密集型和耗时性质，大多数先前的研究侧重于孤立地评估单个参数的影响。因此，快速和系统地确定最佳工艺参数以最大限度地提高益生菌的存活率仍然是药物配方研究中一个重大而未解决的挑战。为了解决这一差距，开发了一种将基于主动学习（AL）的高斯过程回归（GPR）与有限元（FE）建模相结合的综合方法，系统地探索压实参数空间并确定最佳工艺条件。AL中使用的所有数据都是使用FE模型生成的，该模型是专门用于预测片剂过程中益生菌的活力。值得注意的是，集成方法仅在78次迭代后就取得了较高的预测性能，在整个设计空间内预测片剂期间益生菌存活率的决定系数（R2）为0.96。利用训练良好的模型，采用结合阈值滤波的全局随机抽样策略来识别可能产生接近最佳存活率的设计空间区域。此外，在选定的固定主压缩压力下，对压缩速度和预压缩压力的探索可以生成存活率图，从而深入了解益生菌存活率与片剂机械性能之间的相互作用。这项研究证明了混合数据驱动和第一性原理建模方法作为优化益生菌片化过程和加速药物开发的强大策略的潜力。

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引用次数: 0

Structured engineering of self-emulsifying drug delivery systems (SEDDS) via 3D printing: Comprehensive review 基于3D打印的自乳化给药系统（SEDDS）结构工程：综合综述

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-15 DOI: 10.1016/j.ijpx.2025.100416

Induja Govindan, Anjana A. Kailas, K.A. Abutwaibe, Thamizharasan Annadurai, Ujwala Achar, Anup Naha, Srinivas Hebbar

The combination of self-emulsifying drug delivery systems (SEDDS) with three-dimensional printing (3DP) technologies represents an innovative and promising strategy for developing personalised dosage forms. Through precise control over dosage form architecture, controlled drug release kinetics, and individualised therapeutic customisation, 3DP offers distinct and transformative advantages over conventional pharmaceutical formulation approaches. This review focuses on the application of modern 3DP techniques, specifically fused deposition modelling (FDM), semi-solid extrusion (SSE), and drop-on-demand (DoD), in the formulation and production of SEDDS. Each technique is critically evaluated in terms of formulation compatibility, operational mechanisms, and its potential to address the current manufacturing challenges associated with SEDDS. 3DP technologies offer several benefits, including enhanced flexibility in production, the ability to fabricate on demand, and the potential to accommodate complex and personalised therapeutic regimens. However, these methods also face notable limitations, such as material constraints, variability in print quality, mechanical and safety issues, and a lack of clear regulatory guidance. Despite their potential, the use of 3DP in SEDDS development remains relatively unexplored. This review aims to provide a comprehensive overview of the current research landscape, identify existing technological and regulatory barriers, and discuss future prospects for integrating 3DP into next-generation SEDDS formulations.

自乳化给药系统（SEDDS）与三维打印（3DP）技术的结合代表了开发个性化剂型的创新和有前途的策略。通过对剂型结构的精确控制、药物释放动力学的控制和个性化的治疗定制，3d打印与传统的药物配方方法相比具有独特的变革性优势。本文综述了现代3d打印技术在SEDDS配方和生产中的应用，特别是熔融沉积建模（FDM）、半固态挤压（SSE）和按需滴注（DoD）。每种技术都在配方兼容性、操作机制以及解决当前与SEDDS相关的制造挑战的潜力方面进行了严格评估。3d打印技术提供了几个好处，包括提高生产的灵活性，按需制造的能力，以及适应复杂和个性化治疗方案的潜力。然而，这些方法也面临着明显的局限性，如材料限制、打印质量的可变性、机械和安全问题，以及缺乏明确的监管指导。尽管具有潜力，但3d打印技术在SEDDS开发中的应用仍然相对未被探索。本文旨在全面概述当前的研究概况，确定现有的技术和监管障碍，并讨论将3d打印技术整合到下一代SEDDS配方中的未来前景。

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引用次数: 0

Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control 推进癌症放疗：利用放射增敏剂和纳米技术加强肿瘤控制

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-15 DOI: 10.1016/j.ijpx.2025.100419

Fatemeh Shiridokht , Parniya Kehtari , Morteza Eskandani , Alireza Farajollahi , Somayeh Vandghanooni

Cancer affects millions of individuals annually, with radiotherapy playing a crucial role in the treatment of over 70% of cases. Nevertheless, the effectiveness of radiotherapy is frequently limited by tumor radioresistance and the associated toxicity to normal tissues. Radiosensitizers enhance tumor sensitivity to ionizing radiation, optimizing doses and reducing damage. This review evaluates diverse radiosensitizers, including natural compounds (curcumin, resveratrol), chemotherapeutics (cisplatin, doxorubicin), and high-Z nanoparticles (gold, hafnium), which amplify DNA damage and ROS production. Advanced nanocarriers—carbon-, lipid-, and polymer-based—improve targeted delivery, specificity, and bioavailability. Various molecular mechanisms involving proteins such as p53, PARP1, miRNAs (miR-21, miR-155), and siRNAs are discussed in relation to their roles in modulating cell cycle progression, apoptosis, and gene expression to overcome resistance. Radioprotectors like antioxidants and amifostine safeguard normal tissues. Ongoing trials with hafnium oxide and cisplatin regimens show promise. Key findings highlight nanotechnology's role in enhancing radiosensitization via dose enhancement factors and synergistic therapies. Implications include personalized treatments tailored to tumor biology, the reduction of radioresistance through precision medicine and data-driven strategies, and ultimately, the improvement of radiotherapy efficacy and patient outcomes.

癌症每年影响数百万人，其中放疗在70%以上病例的治疗中起着至关重要的作用。然而，放射治疗的有效性经常受到肿瘤放射耐药性和对正常组织的相关毒性的限制。放射增敏剂增强肿瘤对电离辐射的敏感性，优化剂量并减少损伤。本综述评估了多种放射增敏剂，包括天然化合物（姜黄素、白藜芦醇）、化疗药物（顺铂、阿霉素）和高z纳米颗粒（金、铪），它们会放大DNA损伤和ROS的产生。先进的纳米载体-碳，脂质和聚合物-改善靶向递送，特异性和生物利用度。本文讨论了包括p53、PARP1、mirna （miR-21、miR-155）和sirna等蛋白在内的各种分子机制，以及它们在调节细胞周期进程、细胞凋亡和基因表达以克服耐药性中的作用。抗氧化剂和氨磷汀等放射性保护剂可以保护正常组织。正在进行的氧化铪和顺铂方案的试验显示出希望。主要研究结果强调了纳米技术在通过剂量增强因子和协同疗法增强放射致敏方面的作用。其意义包括针对肿瘤生物学量身定制的个性化治疗，通过精确医学和数据驱动策略减少放射耐药，并最终改善放疗疗效和患者预后。

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引用次数: 0

Preparation of colon-targeted pellets loaded with filgotinib/berberine hydrochloride and Their application in ulcerative colitis therapy 非戈替尼/盐酸小檗碱结肠靶向微丸的制备及其在溃疡性结肠炎治疗中的应用

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-15 DOI: 10.1016/j.ijpx.2025.100415

Jinglong Wang , Zhixuan Kuang , Binglian Chen , Chenxi Yan , Bowen Shi , Guofei Li

Ulcerative colitis (UC) is a recurrent-remitting autoimmune disease of the colon, the pathogenesis of which remains incompletely understood. Recent studies have revealed gut dysbiosis and immune imbalance mediated by the JAK-STAT and NF-κB signaling pathways are closely associated with the onset and progression of UC. In particular, the interplay between gut dysbiosis and immune imbalance has become a key factor in the rapid progression of UC, which also contributes to the suboptimal efficacy of existing therapeutic drugs. A growing number of scholars believe that simultaneously regulating gut dysbiosis and immune imbalance to synergistically combat UC may represent a critical breakthrough in UC treatment. Based on this premise, this study utilized extrusion-spheronization and fluidized-bed-coating technologies to prepare colon-targeted pellets co-loaded with berberine hydrochloride and filgotinib, and evaluated their potential for synergistic UC therapy. The results demonstrated the prepared pellets exhibited satisfactory pharmaceutical characteristics, including high sphericity, uniform particle size, and intact coating integrity. Moreover, the drug release behavior of the pellets showed high consistency in both in-vitro and in-vivo settings, displaying distinct pH-responsive release properties that meet the requirements for colon-targeted formulations. Furthermore, the pellets exhibited significant therapeutic effects in DSS-induced UC model, with beneficial changes observed in key indicators such as gut microbiota and immune. Immunohistochemistry, multiplex cytokine assays, and gut microbiota sequencing results all confirmed the synergistic effect of berberine hydrochloride and filgotinib in UC treatment. In conclusion, the findings of this study provide new insights for further research on UC and the development of synergistic UC therapies.

溃疡性结肠炎（UC）是一种复发缓解型结肠自身免疫性疾病，其发病机制尚不完全清楚。近年来的研究表明，由JAK-STAT和NF-κB信号通路介导的肠道生态失调和免疫失衡与UC的发生和发展密切相关。特别是肠道生态失调与免疫失衡之间的相互作用成为UC快速发展的关键因素，这也导致了现有治疗药物的疗效不佳。越来越多的学者认为，同时调节肠道生态失调和免疫失衡，协同对抗UC可能是UC治疗的关键突破。在此前提下，本研究采用挤压滚圆和流化床包衣技术制备了盐酸小檗碱和非戈替尼共载的结肠靶向微球，并对其协同治疗UC的潜力进行了评价。实验结果表明，所制备的微丸具有较高的球形度、均匀的粒径和完整的包被完整性。此外，微丸在体外和体内的药物释放行为均表现出高度一致性，具有明显的ph响应释放特性，符合结肠靶向制剂的要求。此外，微丸在dss诱导的UC模型中表现出显著的治疗效果，在肠道微生物群和免疫等关键指标上观察到有益的变化。免疫组织化学、多种细胞因子检测和肠道菌群测序结果均证实盐酸小檗碱和非戈替尼在UC治疗中的协同作用。总之，本研究结果为UC的进一步研究和UC协同治疗的发展提供了新的见解。

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引用次数: 0

A postoperative in situ drug delivery system based on biphasic drug-release and “Three-in-One” Effect of curcumin to inhibit the recurrence of glioma 基于双相释药和姜黄素“三合一”作用抑制胶质瘤复发的术后原位给药系统

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-12 DOI: 10.1016/j.ijpx.2025.100418

Qiong Liang , Jiangjian Liu , Yanhang Zhuo, Sunhui Chen

The standard treatment for glioma is surgical resection of the tumor followed by postoperative temozolomide-based radio chemotherapy. However, the survival rate remains poor. This study, aiming to address the challenge of postoperative glioma recurrence, developed a reactive oxygen species-sensitive and thermo-sensitive gel to form biphasic drug-release postoperative in situ drug delivery system (PIDDS). This system simultaneously carried free temozolomide, free curcumin, and drug-loaded PLGA nanoparticles. Through a “rapid release + sustained release” biphasic drug-release mode and the “three-in-one” effect of curcumin, it enhanced the chemo sensitization of temozolomide, inhibited the glioma stem cells, and regulated the postoperative recurrence microenvironment, to achieve synergistic tumor recurrence inhibition. In vitro and in vivo experiments have shown this dual-sensitive gel PIDDS had a cumulative drug-release rate of over 88 % within 30 days, significantly extending the median survival time of rats to 57 days, 3 times higher than that of control group, while reducing systemic toxicity. The study has confirmed the PIDDS worked by disrupting DNA repair, inhibiting JAK-STAT stemness pathway, and reprogramming metabolic microenvironment, thus providing a new strategy for precise postoperative treatment of glioma.

胶质瘤的标准治疗是手术切除肿瘤，术后以替莫唑胺为基础的放化疗。然而，存活率仍然很低。本研究针对胶质瘤术后复发的挑战，开发了一种活性氧物种敏感和热敏凝胶，形成双相药物释放术后原位给药系统（PIDDS）。该系统同时携带游离替莫唑胺、游离姜黄素和载药PLGA纳米颗粒。通过姜黄素的“快释+缓释”双相释药模式和“三合一”效应，增强替莫唑胺的化疗增敏，抑制胶质瘤干细胞，调节术后复发微环境，达到协同抑制肿瘤复发的目的。体外和体内实验表明，该双敏凝胶PIDDS在30天内的累积药物释放率超过88%，显著延长大鼠的中位生存时间至57天，是对照组的3倍，同时降低了全身毒性。本研究证实PIDDS通过破坏DNA修复、抑制JAK-STAT干性通路、重编程代谢微环境发挥作用，从而为胶质瘤术后精准治疗提供了新的策略。

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引用次数: 0

An overview of advanced nanocarrier systems for Ibrutinib delivery: overcoming pharmacokinetic barriers and enabling targeted cancer therapy 伊鲁替尼递送的先进纳米载体系统概述：克服药代动力学障碍和实现靶向癌症治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-11 DOI: 10.1016/j.ijpx.2025.100417

Akshay Shetty, Mahesha Keerikkadu, Pragathi Devanand Bangera, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand

Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has transformed the treatment of B-cell malignancies like chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. With its clinical success, IBR is faced with enormous challenges like low aqueous solubility, low oral bioavailability, extensive first-pass metabolism, off-target toxicities, and resistance development. Nanotechnology-based drug delivery systems have been reported to be effective solutions for these issues. This review offers a comprehensive and critical examination of new trends in IBR-loaded nanocarriers, including PEGylated liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanostructured lipid carriers, and hybrid nanoplatforms. These nanocarriers showed improved drug solubility, prolonged circulation, controlled release, cancer-specific targeting, and reduced systemic toxicity. Emphasis on advanced approaches such as ligand-mediated targeting, stimuli-sensitive release, and co-delivery systems designed to optimize therapeutic effects and avoid resistance mechanisms. Preclinical models demonstrated improved bioavailability, improved tumor accumulation, and improved safety profiles of the IBR nanocarriers. This review covers the translational hurdles, regulatory aspects, and commercial tractability of nanocarrier-mediated inhibition of BTK. In summary, nanotechnology provides a revolutionary pathway for maximizing IBR therapy that could facilitate more efficient, safer, and targeted care for patients with hematologic cancers.

Ibrutinib （IBR）是布鲁顿酪氨酸激酶（BTK）的共价抑制剂，已经改变了b细胞恶性肿瘤如慢性淋巴细胞白血病、套细胞淋巴瘤和Waldenström巨球蛋白血症的治疗。随着临床的成功，IBR面临着巨大的挑战，如低水溶性、低口服生物利用度、广泛的首过代谢、脱靶毒性和耐药性的发展。据报道，基于纳米技术的给药系统是解决这些问题的有效方法。本文综述了装载ibr的纳米载体的新趋势，包括聚乙二醇化脂质体、聚合纳米颗粒、树状大分子、固体脂质纳米颗粒、纳米结构脂质载体和混合纳米平台。这些纳米载体具有改善药物溶解度、延长循环、控制释放、癌症特异性靶向和降低全身毒性的特点。强调先进的方法，如配体介导的靶向，刺激敏感释放和共同递送系统，旨在优化治疗效果和避免耐药机制。临床前模型显示IBR纳米载体提高了生物利用度，改善了肿瘤积累，提高了安全性。本文综述了纳米载体介导的BTK抑制的翻译障碍、调控方面和商业可追溯性。总之，纳米技术为最大化IBR治疗提供了一条革命性的途径，可以促进对血液学癌症患者更有效、更安全、更有针对性的治疗。

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引用次数: 0

A novel EGFR-targeted photosensitizer for the theranostics of skin cancer 一种用于治疗皮肤癌的新型egfr靶向光敏剂

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-09 DOI: 10.1016/j.ijpx.2025.100413

Huijuan Li , Huijun Li , Shuang Qi , Xiaohui Tang , Shiqi Zhao , Xin Bian , Baoqing Tian , Hua Zhang , Yuchun Wei , Dianlong Jia , Xinyue Han , Qing Fan

The epidermal growth factor receptor (EGFR) is a critical therapeutic target implicated in the pathogenesis and progression of skin cancer, holding significant promise for enhancing precision diagnosis and treatment efficacy. In this study, we developed ICG-Z_EGFR, a novel EGFR-targeting agent engineered through conjugation of the photosensitizer indocyanine green (ICG) to an EGFR-targeted dimeric affibody (Z_EGFR) for the theranostics of EGFR-positive skin cancer. In vitro, ICG-Z_EGFR-mediated photothermal therapy (PTT) induced significant cell death in EGFR-positive A431 cells, while exhibiting minimal effects on EGFR-negative MLE-12 cells. Compared to free ICG, ICG-Z_EGFR enhanced tumor retention, and significantly improved tumor-targeting capability, making it advantageous for identifying EGFR-positive tumor tissues. Furthermore, ICG-Z_EGFR also exhibited excellent photothermal conversion performance in vivo, and effectively suppressed the growth of A431 tumors through thermal ablation. Importantly, ICG-Z_EGFR demonstrated favorable short-term safety profiles during the in vivo treatment assay. In conclusion, the successfully developed ICG-Z_EGFR in this study, as a novel tumor-targeted photosensitizer, innovatively breaks through the limitations of traditional single-modal treatment. This study would open up new perspectives and pathways for integrated clinical diagnosis and treatment of EGFR-positive skin cancer.

表皮生长因子受体（epidermal growth factor receptor， EGFR）是参与皮肤癌发病和进展的重要治疗靶点，在提高精准诊断和治疗效果方面具有重要前景。在这项研究中，我们开发了ICG-ZEGFR，这是一种新型的egfr靶向药物，通过将光敏剂吲哚青绿（ICG）与egfr靶向二聚体粘附体（ZEGFR）偶联而设计，用于治疗egfr阳性皮肤癌。在体外，icg - zegfr介导的光热疗法（PTT）在egfr阳性的A431细胞中诱导了显著的细胞死亡，而对egfr阴性的MLE-12细胞的影响微乎其微。与游离ICG相比，ICG- zegfr增强了肿瘤滞留，显著提高了肿瘤靶向能力，有利于识别egfr阳性肿瘤组织。此外，ICG-ZEGFR在体内也表现出优异的光热转化性能，通过热消融有效抑制A431肿瘤的生长。重要的是，在体内治疗试验中，ICG-ZEGFR显示出良好的短期安全性。综上所述，本研究成功开发的ICG-ZEGFR作为一种新型肿瘤靶向光敏剂，创新性地突破了传统单模态治疗的局限性。本研究将为egfr阳性皮肤癌的临床综合诊断和治疗开辟新的视角和途径。

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引用次数: 0

Self-healing hydrogel loaded with M2pep-modified recombinant apoferritin enhanced chemotherapy in hepatocellular carcinoma via reprogramming tumor-associated macrophage 装载m2pep修饰的重组铁蛋白的自愈水凝胶通过肿瘤相关巨噬细胞重编程增强肝癌化疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-08 DOI: 10.1016/j.ijpx.2025.100414

Jiayi Qin , Pei Chen , Xin Li , Qingsong Tang , Qingwei Zhao , Haiqin Huang , Yangbo Zhu

Chemotherapy plays an important role in the clinical systemic management of advanced hepatocellular carcinoma (HCC). However, the efficacy of chemotherapy is remarkably suppressed by the tumor microenvironment. After observing the prevalent M2-tumor associated macrophages (TAMs) in clinical HCC specimen, we developed a dual protein drug delivery system, namely, genetically engineered M2 macrophage targeting peptide (M2pep) modified recombinant apoferritin (HFn) for the delivery of "old drug" chloroquine (CQ), and bovine serum albumin (BSA) for the delivery of PTX for the synergistic treatment of HCC. To avoid additional efficacy limitations caused by systemic exposure, BSA@PTX and M2-HFn@CQ were incorporated into a self-healing hydrogel (COT@BP/M2HC) composed of carboxymethyl chitosan, oxidized sodium alginate and tannic acid. The experimental results demonstrated this COT@BP/M2HC hydrogel had good biocompatibility and biodegradability, adhesion, injectability and self-healing properties. It was further confirmed that a single peritumoral injection of COT@BP/M2HC successfully promoted the polarization of M2 TAMs to M1 TAMs, and the M1/M2 ratio increased by 4.63 times compared with the BSA@PTX group, thereby achieving 74.7 % tumor growth inhibition in HCC tumor-bearing mouse models. These findings revealed a potential TAM polarizing effect of CQ and provided a reliable combination strategy for improving HCC chemotherapy efficacy.

化疗在晚期肝细胞癌的临床系统治疗中起着重要的作用。然而，化疗的效果明显受到肿瘤微环境的抑制。在观察临床HCC标本中普遍存在的M2肿瘤相关巨噬细胞（tam）后，我们开发了一种双蛋白药物递送系统，即基因工程M2巨噬细胞靶向肽（M2pep）修饰重组载铁蛋白（HFn）递送“老药”氯喹（CQ），牛血清白蛋白（BSA）递送PTX，协同治疗HCC。为了避免全身暴露造成的额外疗效限制，将BSA@PTX和M2-HFn@CQ掺入由羧甲基壳聚糖、氧化海藻酸钠和单宁酸组成的自愈水凝胶（COT@BP/M2HC）中。实验结果表明，COT@BP/M2HC水凝胶具有良好的生物相容性和生物降解性、粘附性、注射性和自愈性。进一步证实，单次瘤周注射COT@BP/M2HC成功促进M2 tam向M1 tam极化，M1/M2比值较BSA@PTX组提高4.63倍，从而在HCC荷瘤小鼠模型中实现74.7%的肿瘤生长抑制。这些发现揭示了CQ潜在的TAM极化作用，为提高HCC化疗疗效提供了可靠的联合策略。

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引用次数: 0

pH-responsive polymeric nanoparticles for peptide delivery: Synergistic STING pathway activation enhances tumor immunotherapy ph响应聚合物纳米颗粒肽递送：协同STING途径激活增强肿瘤免疫治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-10-06 DOI: 10.1016/j.ijpx.2025.100412

Mengjie Rui , Haidan Tang , Lianglai Gao , Yujiao Hu , Wenyan Liang , Yinfeng Li , Chunlai Feng

Peptides hold great promise in tumor immunotherapy, but suffer from poor stability and short systemic circulation. To overcome these challenges, we developed a pH-responsive nanodelivery systems (P-NPs) based on the amphiphilic block polymer PEO-PC7A. In addition to its role in peptide encapsulation and protection, PEO-PC7A intrinsically acted as a stimulator of the interferon genes (STING) agonist, activating the cGAS-STING signaling pathway and remodeling the immunosuppressive tumor microenvironment. P-NPs were successfully prepared via a self-assembly technique, yielding nanoparticles with a uniform diameter of 91.2 ± 3.5 nm. Their pH-responsive behavior was confirmed by significant change in particle size and accelerated peptide release under acidic conditions. In vitro, P-NPs effectively increased the cytotoxic activity of T cells and induced higher interleukin-2 (IL-2) secretion compared to free peptide. In a 4 T1 tumor-bearing mouse model, intravenous administration of P-NPs achieved greater tumor growth inhibition and higher intratumoral interferon-γ (IFN-γ) levels than free peptide, with minimal systemic toxicity and no significant impact on body weight. Overall, our study presented a novel multifunctional peptide nanocarrier that enhanced tumor immunotherapy efficacy by concurrently improving peptide delivery and stimulating innate immunity, providing a promising foundation for the further development of innovative combination cancer immunotherapy strategies.

多肽在肿瘤免疫治疗中具有广阔的应用前景，但其稳定性差、体循环短。为了克服这些挑战，我们开发了一种基于两亲嵌段聚合物PEO-PC7A的ph响应纳米递送系统（P-NPs）。PEO-PC7A除了具有肽包封和保护作用外，本质上还作为干扰素基因（STING）激动剂的刺激因子，激活cGAS-STING信号通路，重塑免疫抑制的肿瘤微环境。通过自组装技术成功制备了P-NPs，得到了均匀直径为91.2±3.5 nm的纳米颗粒。在酸性条件下，颗粒大小的显著变化和肽释放的加速证实了它们的ph响应行为。在体外，与游离肽相比，P-NPs能有效提高T细胞的细胞毒活性，诱导更高的白细胞介素-2 （IL-2）分泌。在4 T1荷瘤小鼠模型中，静脉给药P-NPs比游离肽具有更大的肿瘤生长抑制作用和更高的瘤内干扰素-γ (IFN-γ)水平，具有最小的全身毒性，对体重没有显著影响。总之，我们的研究提出了一种新的多功能肽纳米载体，通过同时改善肽递送和刺激先天免疫来提高肿瘤免疫治疗效果，为进一步开发创新的肿瘤联合免疫治疗策略提供了有希望的基础。

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引用次数: 0