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Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention. 外泌体在骨科疾病中的细胞通讯和治疗剂:从机制到干预。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-13 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S582197
Jianwen Zhang, Minjie Zhang, Xiaoru Ren, Mengying Li, Yiwen Zhu, Dan Shou, Yang Zhang

Exosome-mediated intercellular communication has become a critical mechanism in the pathogenesis, progression, and regenerative repair of orthopedic diseases. By delivering bioactive molecules, exosomes dynamically regulate bone remodeling, cartilage homeostasis, and inflammatory responses-processes that are commonly disrupted in conditions such as osteoporosis, osteoarthritis, and bone non-union. Current therapeutic approaches often fail to achieve complete tissue repair or reverse disease progression, representing a major clinical challenge in orthopedics. This systematic review examines how exosome secretion, cargo loading, and cellular uptake are modulated by physical, chemical, biological, and pharmacological factors, thereby influencing disease progression and tissue repair. Furthermore, we evaluate the translational potential of engineered exosomes as targeted therapeutic strategies and analyze the dual dilemmas currently faced in exosome research and clinical translation: on one hand, exosomes themselves encounter technical bottlenecks such as standardization of isolation, drug-loading efficiency, large-scale production, and targeted delivery; on the other hand, their clinical application remains limited by unclear in vivo metabolic mechanisms, lack of efficacy evaluation systems, and insufficient clinical validation. Overcoming these challenges will be essential to advancing the real-world clinical application of exosomes in orthopedics.

外泌体介导的细胞间通讯已成为骨科疾病发病、进展和再生修复的重要机制。通过传递生物活性分子,外泌体动态调节骨重塑、软骨稳态和炎症反应——这些过程通常在骨质疏松症、骨关节炎和骨不连等疾病中被破坏。目前的治疗方法往往无法实现完全的组织修复或逆转疾病进展,这是骨科的主要临床挑战。这篇系统综述探讨了外泌体分泌、货物装载和细胞摄取如何受到物理、化学、生物和药理学因素的调节,从而影响疾病进展和组织修复。此外,我们评估了工程外泌体作为靶向治疗策略的翻译潜力,并分析了目前外泌体研究和临床翻译面临的双重困境:一方面,外泌体本身面临分离标准化、载药效率、大规模生产和靶向递送等技术瓶颈;另一方面,由于体内代谢机制不明确,缺乏疗效评价体系,临床验证不足,其临床应用仍然受到限制。克服这些挑战对于推进外泌体在骨科中的实际临床应用至关重要。
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引用次数: 0
An Injectable Photothermal Responsive Liposome Hydrogel Co-Loaded with Bufalin, Apatinib, and IR820 for Inhibiting Postoperative Recurrence of Colon Cancer. 一种可注射光热反应脂粒水凝胶,共载蟾毒灵、阿帕替尼和IR820抑制结肠癌术后复发。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-13 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S575430
Ai-Jia Wang, Huan Tian, Zhan-Peng Wang, Jiang-Xue Cheng, Jing Sun, Feng Zhao, Ya-Jun Shi, Xiao-Fei Zhang, Jun-Bo Zou, Fei Luan, Bing-Tao Zhai, Dong-Yan Guo

Background: Colon cancer ranks as the third most common malignant tumor globally. Due to incomplete surgical resection and the multidrug resistance of tumor cells, it exhibits a high postoperative recurrence rate. Consequently, there is an urgent need to develop novel therapeutic strategies to inhibit postoperative recurrence of colon cancer.

Methods: Thermosensitive liposomes (Bu&Ap-Lip) co-loaded with bufalin (Bu) and apatinib (Ap) were prepared via the thin-film hydration method, with optimization of Prescription Processes. Bu&Ap-Lip was co-encapsulated with new indocyanine green (IR820) within an injectable PLGA-PEG-PLGA hydrogel, establishing a photothermally responsive composite hydrogel (Bu&Ap-Lip@IR820 Gel). The system characterized the physicochemical properties, rheological characteristics, and drug release behavior of the hydrogel, and further evaluated its in vitro antitumor activity and in vivo efficacy against postoperative recurrence of colon cancer.

Results: Bu&Ap-Lip@IR820 Gel demonstrated excellent injectability and photothermally responsive drug-release properties. In vitro cellular experiments demonstrated that Bu&Ap-Lip@IR820 Gel effectively inhibited tumor cell migration, invasion, and angiogenesis. In vivo studies revealed that this liposome hydrogel prolonged local drug retention. When combined with near-infrared light irradiation, Bu&Ap-Lip@IR820 Gel significantly suppressed tumor recurrence while exhibiting favorable in vivo biocompatibility.

Conclusion: This study developed a NIR-responsive composite liposome hydrogel integrating Bu multi-targeted antitumor properties, Ap anti-angiogenic effects, and IR820 photothermal therapeutic advantages. Through near-infrared responsiveness, it achieves localized precision drug release, effectively suppressing postoperative recurrence. This provides a novel and promising strategy for the clinical prevention and treatment of colon cancer recurrence.

背景:结肠癌是全球第三大最常见的恶性肿瘤。由于手术切除不完全,肿瘤细胞耐多药,术后复发率高。因此,迫切需要开发新的治疗策略来抑制结肠癌术后复发。方法:采用薄膜水合法制备了蟾毒灵(Bu)和阿帕替尼(Ap)共载的热敏脂质体(Bu&Ap-Lip),并对处方工艺进行了优化。将Bu&Ap-Lip与新型吲哚菁绿(IR820)共包被在可注射的PLGA-PEG-PLGA水凝胶中,建立光热响应的复合水凝胶(bu&Ap-Lip@IR820 Gel)。该系统表征了水凝胶的理化性质、流变学特性和药物释放行为,并进一步评价了其体外抗肿瘤活性和体内抗结肠癌术后复发的疗效。结果:bu&Ap-Lip@IR820凝胶具有良好的注射性和光热响应性释药特性。体外细胞实验表明,bu&Ap-Lip@IR820凝胶能有效抑制肿瘤细胞的迁移、侵袭和血管生成。体内研究表明,这种脂质体水凝胶延长了局部药物潴留。当与近红外光照射联合使用时,Bu&Ap-Lip@IR820凝胶可显著抑制肿瘤复发,同时具有良好的体内生物相容性。结论:本研究开发了一种集Bu多靶点抗肿瘤、Ap抗血管生成和IR820光热治疗优势于一体的nir响应型复合脂质体水凝胶。通过近红外响应性,实现局部精准药物释放,有效抑制术后复发。这为临床预防和治疗结肠癌复发提供了一种新颖而有前景的策略。
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引用次数: 0
Nanotechnology-Enabled Diagnosis and Treatment of Hepatocellular Carcinoma: Theranostics, Combination Regimens, and Translation. 纳米技术支持的肝细胞癌的诊断和治疗:治疗学、联合方案和转化。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-12 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S581911
Siyao Wang, Yang Wu, Miao Yuan, Jing Zheng, Chaoran Wang, Jiarong Wang, Yifan Zheng, Qiaoyun Yang, Mengran Xu, Baiqi Wang

This manuscript explores the innovative application of nanotechnology in the diagnosis and treatment of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Emphasizing the synergistic potential of nanotechnology, the paper discusses advanced nanomaterials and techniques, such as targeted drug delivery systems, nanoparticle-based imaging, and multi-modal therapy, which enhance the precision and efficacy of HCC interventions. Nanotechnology offers significant improvements in early diagnosis through enhanced imaging capabilities and tumor-specific biomarkers, enabling more accurate detection of HCC at its early stages. Furthermore, it enables the development of novel therapeutic strategies, including the targeted delivery of chemotherapeutic agents, gene therapies, and immunotherapies, minimizing side effects and improving patient outcomes. The manuscript also highlights challenges such as bio-barrier penetration, biocompatibility, and the high production costs associated with nanomedicine. Despite these obstacles, the integration of nanotechnology with artificial intelligence and personalized medicine promises a transformative future for HCC treatment. This review underscores the pivotal role of nanotechnology in advancing both the diagnostic and therapeutic landscapes for HCC, offering a new frontier for improving survival rates and quality of life for patients.

本文探讨了纳米技术在肝细胞癌(HCC)诊断和治疗中的创新应用,HCC是全球癌症相关死亡的主要原因。强调纳米技术的协同潜力,本文讨论了先进的纳米材料和技术,如靶向药物输送系统、纳米颗粒成像和多模式治疗,这些都提高了HCC干预的准确性和有效性。纳米技术通过增强成像能力和肿瘤特异性生物标志物,在早期诊断方面提供了重大改进,使HCC在早期阶段得到更准确的检测。此外,它能够开发新的治疗策略,包括化疗药物的靶向递送,基因疗法和免疫疗法,最大限度地减少副作用并改善患者的预后。该手稿还强调了诸如生物屏障渗透、生物相容性以及与纳米药物相关的高生产成本等挑战。尽管存在这些障碍,纳米技术与人工智能和个性化医疗的结合有望为HCC治疗带来革命性的未来。这篇综述强调了纳米技术在推进HCC诊断和治疗领域的关键作用,为提高患者的生存率和生活质量提供了新的前沿。
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引用次数: 0
Pearl Powder Fluorescent Carbon Dots Alleviate Neuroinflammation in Cerebral Ischemia/Reperfusion Through Suppression of Anxa2/NF-κB Signaling Pathway. 珍珠粉荧光碳点通过抑制Anxa2/NF-κB信号通路减轻脑缺血再灌注神经炎症。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-11 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S567974
Pongsigeraxi Borjigin, Caixia Deng, Rilaga Su, Juan Li, Ying Ying, Yingsong Chen, Tegexibaiyin Wang

Purpose: This study aimed to enzymatically synthesize pearl powder fluorescent carbon dots (PFCDs) and investigate their neuroprotective potential against cerebral ischemia/reperfusion injury (CIRI) by modulating the Anxa2/NF-κB signaling pathway.

Methods: PFCDs were synthesized through enzymatic digestion and characterized. Neuroprotective effects were assessed using an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC12 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. Cell viability, neurological function, cerebral infarct volume, and neuronal injury were evaluated. Expression of Anxa2/NF-κB signaling pathway proteins and inflammatory cytokines (TNF-α, IL-6, IL-1β) was analyzed by Western blot, immunofluorescence, and ELISA.

Results: The synthesized PFCDs exhibited an organic-inorganic hybrid structure, uniform particle size below 10 nm, and distinctive optical properties. In vitro, PFCDs enhanced cell viability under OGD/R conditions, inhibited phosphorylation of Anxa2 and NF-κB p65, and reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In vivo, treatment with PFCDs in MCAO/R rats improved neurological function, reduced cerebral infarct volume, and alleviated neuronal injury. These protective effects were linked to downregulation of the Anxa2/NF-κB signaling pathway and reduced serum levels of inflammatory cytokines.

Conclusion: We successfully achieved the enzymatic synthesis of carbon dots from pearl powder, characterized by a unique organic-inorganic hybrid structure. PFCDs effectively alleviated CIRI-induced neuroinflammation by suppressing the Anxa2/NF-κB signaling pathway, highlighting their therapeutic potential as a nanomedicine derived from natural products.

目的:通过酶促合成珍珠粉荧光碳点(PFCDs),研究其通过调节Anxa2/NF-κB信号通路对脑缺血再灌注损伤的神经保护作用。方法:采用酶解法合成PFCDs,并对其进行表征。采用PC12细胞体外氧-葡萄糖剥夺/再氧合(OGD/R)模型和大脑中动脉闭塞/再灌注(MCAO/R)大鼠模型评估神经保护作用。评估细胞活力、神经功能、脑梗死体积和神经元损伤。Western blot、免疫荧光、ELISA检测各组小鼠Anxa2/NF-κB信号通路蛋白及炎症因子(TNF-α、IL-6、IL-1β)的表达。结果:合成的PFCDs具有有机-无机杂化结构,粒径均匀,粒径小于10 nm,光学性能优异。在体外,PFCDs增强OGD/R条件下的细胞活力,抑制Anxa2和NF-κB p65的磷酸化,减少促炎细胞因子(TNF-α、IL-6、IL-1β)的分泌。在体内,pfcd治疗MCAO/R大鼠可改善神经功能,减少脑梗死体积,减轻神经元损伤。这些保护作用与下调Anxa2/NF-κB信号通路和降低血清炎症细胞因子水平有关。结论:我们成功地实现了珍珠粉碳点的酶促合成,具有独特的有机-无机杂化结构。PFCDs通过抑制Anxa2/NF-κB信号通路有效缓解ciri诱导的神经炎症,凸显其作为天然产物衍生的纳米药物的治疗潜力。
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引用次数: 0
The Role of Bacterial Outer Membrane Vesicles in Tumor Development: Facts, Potential Applications and Future Perspectives. 细菌外膜囊泡在肿瘤发展中的作用:事实、潜在应用和未来展望。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-11 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S582600
Zheng Gu, Menglei Zhang, Fang Shen, Junhao Chen, Yuanyuan Gu, Yingxin Gong, Qingxuan Xue, Hang Zhou, Yueheng Liu, Siqi Shao, Yue Zhang, Jiming Bai, Keqin Hua, Guannan Zhou, Jingxin Ding

Bacterial outer membrane vesicles (OMVs), nanosized lipid bilayer particles released by both Gram-negative and Gram-positive bacteria, are emerging as crucial mediators of host-microbe interactions in cancer biology. This review synthesizes current evidence on how OMVs modulate tumor initiation, progression, and therapeutic responses through multifaceted mechanisms aligned with the 14 hallmarks of cancer. Studies demonstrate that OMVs can either promote or inhibit neoplastic processes depending on their bacterial origin and cargo composition. Tumor-promoting OMVs enhance proliferative signaling, drive epithelial-mesenchymal transition, facilitate metastatic dissemination via barrier disruption and angiogenesis, and weaken antitumor immunity. Conversely, other OMVs exert antineoplastic effects by triggering intrinsic apoptosis, cell-cycle arrest, immunogenic cell death, and remodeling of the tumor immune microenvironment. Pre-clinical studies further highlight the translational potential of engineered OMVs as precision nano-vaccines, immunotherapeutic agents, and adjuvants that synergize with immune checkpoint blockade, chemotherapy, or photothermal therapy while minimizing systemic toxicity. Future directions could focus on mapping of OMV cargo-pathway-phenotype networks by multidisciplinary methods, programmable vesicle design using synthetic biology, and real-time microbiome-OMV monitoring in early-phase clinical trials to enable individualized onco-therapeutics. Collectively, OMVs represent a versatile platform to bidirectionally regulate oncogenesis and therapeutic responses. Exploiting their molecular plasticity through rational engineering and precision medicine frameworks would bring transformative potential for cancer prevention, diagnosis, and treatment.

细菌外膜囊泡(OMVs)是由革兰氏阴性和革兰氏阳性细菌释放的纳米级脂质双层颗粒,在癌症生物学中成为宿主-微生物相互作用的重要介质。这篇综述综合了目前关于omv如何通过与14种癌症特征相一致的多方面机制调节肿瘤的发生、进展和治疗反应的证据。研究表明,omv可以促进或抑制肿瘤过程,这取决于它们的细菌来源和货物组成。促进肿瘤的omv增强增殖信号,驱动上皮-间质转化,通过屏障破坏和血管生成促进转移性传播,并削弱抗肿瘤免疫。相反,其他omv通过触发内在凋亡、细胞周期阻滞、免疫原性细胞死亡和肿瘤免疫微环境重塑来发挥抗肿瘤作用。临床前研究进一步强调了工程omv作为精密纳米疫苗、免疫治疗剂和佐剂的转化潜力,这些佐剂可与免疫检查点阻断、化疗或光热疗法协同作用,同时将全身毒性降到最低。未来的方向可能集中在通过多学科方法绘制OMV货物通路表型网络,使用合成生物学进行可编程囊泡设计,以及在早期临床试验中实时监测微生物组-OMV以实现个体化肿瘤治疗。总的来说,omv代表了一个双向调节肿瘤发生和治疗反应的多功能平台。通过合理的工程和精确的医学框架来开发它们的分子可塑性,将为癌症的预防、诊断和治疗带来革命性的潜力。
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引用次数: 0
Enhancement of Psoriasis Treatment by Phellodendri Chinensis Cortex Carbon Dots (PCC-CDs) Through Modulation of the HMGB1/TLR4/MAPK/NF-κB Pathway. 黄柏皮质碳点通过调控HMGB1/TLR4/MAPK/NF-κB通路增强银屑病的治疗作用
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-10 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S578399
Xinrong Tian, Hui Kong, Shuxian Wang, Xiwen Zhang, Chenxin He, Yan Huang, Ruiyan Liu, Ertong Dai, Guojiao Shang, Yue Zhang, Cheng Jinjun, Zhanxue Sun, Huihua Qu, Yan Zhao

Background: Psoriasis is a chronic, debilitating inflammatory skin disorder mediated by the immune system. It is characterized by excessive keratinocyte proliferation and abnormal differentiation, leading to symptoms that significantly impair the quality of life of affected individuals. Despite extensive research, no effective drugs are currently available to completely inhibit the progression of psoriasis.

Purpose: This study aims to explore the therapeutic potential and underlying mechanisms of Phellodendron chinense charcoal carbon dots (PCC-CDs) in treating psoriasis. PCC-CDs have recently garnered attention due to their sustained anti-inflammatory properties and unique bioavailability.

Methods: This study explores the therapeutic potential and underlying mechanisms of PCC-CDs in psoriasis treatment via detailed pharmacological experiments in an imiquimod (IMQ)-induced mouse model, including topical PCC-CDs application, inflammatory mediator detection, histopathological assessment of tissue damage, and transcriptomic as well as molecular biology analyses focusing on the modulation of the HMGB1/TLR4 and MAPK/NF-κB inflammatory signaling pathways.

Results: In the IMQ-induced mouse model, PCC-CDs effectively suppressed the levels of inflammatory mediators and reduced histopathological damage. Molecular analyses revealed that PCC-CDs may exert their therapeutic effects by modulating the inflammatory response mediated by the HMGB1/TLR4 pathway, primarily through inhibiting protein expression in the MAPK/NF-κB signaling cascade. The application of PCC-CDs resulted in a significant reduction in psoriasis-like symptoms in IMQ-induced mice, including marked improvements in erythema, scaling, and pruritus.

Conclusion: PCC-CDs offer a promising new approach to the clinical management of psoriasis. Their ability to provide sustained anti-inflammatory effects and distinctive bioavailability makes them a potential candidate for further development as a therapeutic agent. This study highlights the importance of PCC-CDs in modulating key inflammatory pathways, offering hope for improved treatment options for individuals suffering from psoriasis.

背景:银屑病是一种由免疫系统介导的慢性、衰弱性炎症性皮肤病。它的特点是角质细胞过度增殖和异常分化,导致显著损害患者生活质量的症状。尽管有广泛的研究,目前还没有有效的药物可以完全抑制牛皮癣的进展。目的:探讨黄柏炭炭点(PCC-CDs)治疗银屑病的治疗潜力及其作用机制。由于其持续的抗炎特性和独特的生物利用度,pcc - cd最近引起了人们的关注。方法:本研究通过咪喹莫特(IMQ)诱导小鼠模型的详细药理学实验,探索PCC-CDs在银屑病治疗中的治疗潜力和潜在机制,包括局部应用PCC-CDs,炎症介质检测,组织损伤的组织病理学评估,以及转录组学和分子生物学分析,重点是HMGB1/TLR4和MAPK/NF-κB炎症信号通路的调节。结果:在imq诱导的小鼠模型中,PCC-CDs可有效抑制炎症介质水平,减轻组织病理学损伤。分子分析显示,PCC-CDs可能通过抑制MAPK/NF-κB信号级联中的蛋白表达,通过调节HMGB1/TLR4通路介导的炎症反应来发挥其治疗作用。PCC-CDs的应用显著减轻了imq诱导小鼠的牛皮癣样症状,包括红斑、脱屑和瘙痒的显著改善。结论:pcc - cd为银屑病的临床治疗提供了一种有前景的新方法。它们提供持续抗炎作用的能力和独特的生物利用度使它们成为进一步开发治疗药物的潜在候选者。这项研究强调了PCC-CDs在调节关键炎症通路中的重要性,为改善牛皮癣患者的治疗选择提供了希望。
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引用次数: 0
Nanoparticles in the Treatment of Renal Fibrosis. 纳米颗粒治疗肾纤维化。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-10 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S585576
Ying Wu, Wen Zhang, Li'ou Zhu, Lili Liu

Renal fibrosis represents a key pathological hallmark of chronic kidney disease (CKD), a prevalent condition worldwide that currently lacks effective therapies. Nanotechnology offers transformative potential for renal fibrosis treatments. Engineered nanoparticles (NPs), with tunable physicochemical properties such as size, surface charge, and shape, enable targeted and controlled drug delivery. Furthermore, active targeting strategies can increase nanoparticle uptake by specific cell types or structures in kidneys. Although nanomedicine-based strategies for renal fibrosis remain at an early, predominantly preclinical stage, accumulating evidence from experimental models suggests substantial potential for improving therapeutic precision and efficacy in fibrotic kidney disease. This review integrates recent insights into the pathogenesis of renal fibrosis, NP design strategies, along with advances in NP-based therapeutics, highlighting nanomedicine as a promising approach for precise and effective intervention in CKD-associated renal fibrosis.

肾纤维化是慢性肾脏疾病(CKD)的一个关键病理标志,慢性肾脏疾病是一种全球普遍存在的疾病,目前缺乏有效的治疗方法。纳米技术为肾纤维化治疗提供了变革性的潜力。工程纳米颗粒(NPs)具有可调的物理化学性质,如大小、表面电荷和形状,可以实现靶向和受控的药物输送。此外,主动靶向策略可以增加肾脏中特定细胞类型或结构对纳米颗粒的摄取。尽管基于纳米药物治疗肾纤维化的策略仍处于早期,主要是临床前阶段,但从实验模型中积累的证据表明,在提高纤维化肾病的治疗精度和疗效方面具有巨大的潜力。本综述整合了近期对肾纤维化发病机制、NP设计策略以及基于NP的治疗方法的研究进展,强调了纳米药物作为一种有前景的方法,可以精确有效地干预ckd相关肾纤维化。
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引用次数: 0
Design Evolution of Curcumin-Loaded Nanostructured Lipid Carriers: Formulation Strategies, Functional Modifications, and Mechanistic-Translational Perspectives. 姜黄素负载的纳米结构脂质载体的设计演变:配方策略,功能修饰和机械翻译的观点。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-10 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S586727
Ikra Nurohman, Cecep Suhandi, Anis Yohana Chaerunisaa, Gofarana Wilar, Garnadi Jafar, Sriwidodo Sriwidodo

Curcumin possesses broad therapeutic potential but remains severely limited by poor solubility, instability, and low systemic bioavailability. Nanostructured lipid carriers (NLCs) have emerged as an advanced lipid-based delivery platform capable of overcoming these constraints through optimized lipid organization, high drug-loading capacity, and tunable surface functionality. This review provides a comprehensive examination of the design evolution of curcumin-loaded NLCs (Cur-NLCs), encompassing core components, formulation strategies, preparation techniques, and quality determinants that govern physicochemical and biological performance. Evidence-based classification of formulation approaches is presented, highlighting single-drug, co-loaded, and surface-modified or functionally engineered NLC systems and their respective therapeutic advantages. Mechanistic insights are discussed to elucidate how NLCs enhance curcumin's stability, absorption, intracellular trafficking, and controlled release. Current challenges, including formulation heterogeneity, scalability, long-term stability, and translational readiness, are critically evaluated, alongside emerging clinical observations from engineered NLCs that further underscore their translational relevance. From a translational standpoint, the review identifies NLC designs based on pharmaceutically accepted lipids, scalable preparation methods, and minimal surface complexity as the most feasible candidates for near-term clinical development, while more elaborate multifunctional or ligand-modified systems are discussed as promising but longer-term strategies. However, the progress outlined in this review highlights NLCs as a highly adaptable platform capable of unlocking curcumin's full pharmacological potential and accelerating its pathway toward therapeutic applicability.

姜黄素具有广泛的治疗潜力,但由于溶解度差、不稳定性和低的全身生物利用度,姜黄素仍然受到严重限制。纳米结构脂质载体(nlc)已经成为一种先进的基于脂质的递送平台,能够通过优化的脂质组织、高载药能力和可调的表面功能来克服这些限制。本文综述了姜黄素负载NLCs (curc -NLCs)的设计演变,包括核心成分、配方策略、制备技术和控制物理化学和生物性能的质量决定因素。提出了基于证据的配方方法分类,重点介绍了单药、共载、表面修饰或功能工程的NLC系统及其各自的治疗优势。本文讨论了NLCs如何增强姜黄素的稳定性、吸收、细胞内运输和控制释放的机制。目前面临的挑战,包括配方的异质性、可扩展性、长期稳定性和转化准备性,都得到了严格的评估,同时,来自工程化NLCs的新临床观察进一步强调了它们的转化相关性。从翻译的角度来看,该综述确定了基于药学上可接受的脂质、可扩展的制备方法和最小表面复杂性的NLC设计是近期临床开发中最可行的候选方案,而更复杂的多功能或配体修饰系统则是有前途的长期策略。然而,本综述中概述的进展强调了NLCs作为一种高度适应性的平台,能够释放姜黄素的全部药理潜力并加速其治疗适用性。
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引用次数: 0
Intratracheal Administration of pH-Responsive Nanomicelles: A More Effective Strategy for Enhanced Intracellular Drug Delivery in Lung Cancer Treatment. 气管内给予ph反应性纳米胶束:在肺癌治疗中增强细胞内药物传递的更有效策略。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-10 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S555824
Luting Lin, Guowei Wang, Jie Zhang, Jingming Luo, Xudong Fan, Jianqing Gao, Xinjun Cai

Background: The efficacy of chemotherapy for treating lung cancer is hindered by insufficient intracellular drug utilisation. Moreover, non-targeted distribution often leads to severe side effects, resulting in poor prognosis and low patient compliance. Therefore, a more effective strategy is required to achieve effective treatment. In this study, we aimed to develop a pH-responsive nanoplatform for intratracheal administration to enhance drug accumulation in lung cancer tissues and promote the accumulation of drugs within tumour cells.

Results: A self-assembled nanomicelle named SN-38@PEG-PMMSD (PPM) was constructed using a cinnamaldehyde synthetic carrier material loaded with SN-38 and nanoprecipitation. Intratracheal administration enhanced the accumulation of PPM within the lungs and tumors (the fold increase in lung accumulation following intratracheal (i.t.) were 49.63-fold higher than intravenous (i.v.) delivery at the 48-hour timepoint). Owing to its small size, PPM can easily penetrate deep into tumour tissues. The micro-acidic environment characteristic of tumours increases the efficiency of tumour cell uptake of PPM. This triggered a pH-responsive reaction in the acidic lysosomal milieu, leading to dissociation of PPM and the regeneration of cinnamaldehyde while releasing SN-38. Cinnamaldehyde acted as a reactive oxygen species (ROS) amplifier, facilitating ROS generation. Elevated ROS levels, in conjunction with SN-38, resulted in strong antitumor effects.

Conclusion: In summary, Intratracheal administration of pH-responsive PPM is anticipated to enhance drug accumulation in tumour tissues, improve drug uptake by tumour cells, and achieve effective treatment of lung cancer.

背景:细胞内药物利用不足阻碍了化疗治疗肺癌的疗效。此外,非靶向分布往往导致严重的副作用,导致预后差,患者依从性低。因此,需要更有效的策略来实现有效的治疗。在这项研究中,我们旨在开发一种ph响应纳米平台,用于气管内给药,以增强药物在肺癌组织中的积累,并促进药物在肿瘤细胞内的积累。结果:以肉桂醛为载体,负载SN-38,通过纳米沉淀法构建了自组装纳米胶束SN-38@PEG-PMMSD (PPM)。气管内给药增强了肺和肿瘤内PPM的积累(在48小时时间点,气管内(i.t)给药后肺部积累增加了49.63倍,比静脉(i.v)给药高)。由于其体积小,PPM可以很容易地渗透到肿瘤组织深处。肿瘤的微酸性环境特征增加了肿瘤细胞摄取PPM的效率。这在酸性溶酶体环境中引发了ph响应反应,导致PPM的解离和肉桂醛的再生,同时释放SN-38。肉桂醛作为活性氧(ROS)放大器,促进ROS的生成。升高的ROS水平,结合SN-38,产生了很强的抗肿瘤作用。结论:综上所述,气管内给药ph响应性PPM有望增强药物在肿瘤组织中的蓄积,改善肿瘤细胞对药物的摄取,实现肺癌的有效治疗。
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引用次数: 0
From Barrier to Gateway: Nanomaterials Reshaping the Tumor Microenvironment for Therapy. 从屏障到通道:纳米材料重塑肿瘤微环境治疗。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2026-03-10 eCollection Date: 2026-01-01 DOI: 10.2147/IJN.S573490
Mina Xie, Wanyu Sun, Dongping Hu, Lu Liu, Caiwen Han, Wenhan Liu, Lede Liu, Xiaojiang Bao, Weisheng Zhang, Xiangyong Hao, Yongqiang Zhou

The tumor microenvironment constitutes the external condition that supports the survival and development of tumor cells. It promotes tumor cell proliferation and survival by secreting various cytokines and the provision of nutritional support, thereby driving tumor advancement. However, its structural density and complex composition pose significant barriers to drug delivery and therapeutic intervention, necessitating the development of advanced techniques for effective penetration. In recent years, nanotechnology, characterized by its distinctive physicochemical properties and excellent targeting and regulatory capabilities, has shown tremendous potential in overcoming the tumor microenvironment barriers, garnering significant research interest. This paper systematically summarizes the formation mechanisms of various TME subtypes, including immunosuppressive, metabolic, acidic, hypoxic, stromal, mechanical, microbial, inflammatory, and neural TME. It analyzes the principal challenges faced by nanomaterials in regulating these microenvironments, focuses on research strategies and application prospects of nanomaterials across different subtype microenvironments, and proposes novel directions for future investigation. The objective is to facilitate breakthroughs in the translational application of nanomaterials from mechanistic innovation to clinical practice.

肿瘤微环境是支持肿瘤细胞生存和发育的外部条件。它通过分泌各种细胞因子和提供营养支持来促进肿瘤细胞的增殖和存活,从而推动肿瘤的进展。然而,其结构密度和复杂的组成对药物输送和治疗干预构成了重大障碍,需要开发先进的有效渗透技术。近年来,纳米技术以其独特的物理化学性质和优异的靶向调控能力,在克服肿瘤微环境障碍方面显示出巨大的潜力,引起了人们的广泛关注。本文系统总结了各种TME亚型的形成机制,包括免疫抑制性、代谢性、酸性、缺氧性、间质性、机械性、微生物性、炎症性和神经性TME。分析了纳米材料调控这些微环境所面临的主要挑战,重点讨论了纳米材料在不同亚型微环境中的研究策略和应用前景,并提出了未来研究的新方向。目标是促进纳米材料从机械创新到临床实践的转化应用突破。
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引用次数: 0
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International Journal of Nanomedicine
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