Pub Date : 2025-12-11DOI: 10.1016/j.nano.2025.102889
Chao Zhu, Chenxu Guo, Ligong Zhang, Jun Qian, Mingliang Zhang
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy driven by glycolysis and immune evasion, with limited therapeutic options. This study develops RGD-modified glucose oxidase-loaded liposomes (RGD-Lipo@GOx) to target TNBC by modulating the MIF/NR3C2 axis, aiming to inhibit glycolysis and remodel the immune microenvironment. RGD-Lipo@GOx exhibited high encapsulation efficiency and tumor specificity. Bioinformatics analyses confirmed upregulated MIF and downregulated NR3C2 in TNBC. In vitro, RGD-Lipo@GOx suppressed glycolysis, migration, and invasion in MDA-MB-231 and BT-549 cells, upregulating NR3C2 and inhibiting MIF and PI3K/AKT signaling. In vivo, a TNBC xenograft model demonstrated enhanced tumor targeting, significant growth inhibition, and reduced glycolysis without systemic toxicity. These results highlight RGD-Lipo@GOx's potential as a nanotherapeutic platform that disrupts TNBC's metabolic and immune evasion mechanisms. Its high efficacy and safety suggest potential for clinical translation, particularly in combination with immunotherapies, and applicability to other glycolysis-driven cancers, advancing nanomedicine for precision oncology.
{"title":"RGD-Lipo@GOx: A nanotherapeutic strategy for targeting glycolysis and immune evasion in triple-negative breast cancer","authors":"Chao Zhu, Chenxu Guo, Ligong Zhang, Jun Qian, Mingliang Zhang","doi":"10.1016/j.nano.2025.102889","DOIUrl":"10.1016/j.nano.2025.102889","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive malignancy driven by glycolysis and immune evasion, with limited therapeutic options. This study develops RGD-modified glucose oxidase-loaded liposomes (RGD-Lipo@GOx) to target TNBC by modulating the MIF/NR3C2 axis, aiming to inhibit glycolysis and remodel the immune microenvironment. RGD-Lipo@GOx exhibited high encapsulation efficiency and tumor specificity. Bioinformatics analyses confirmed upregulated MIF and downregulated NR3C2 in TNBC. <em>In vitro</em>, RGD-Lipo@GOx suppressed glycolysis, migration, and invasion in MDA-MB-231 and BT-549 cells, upregulating NR3C2 and inhibiting MIF and PI3K/AKT signaling. <em>In vivo</em>, a TNBC xenograft model demonstrated enhanced tumor targeting, significant growth inhibition, and reduced glycolysis without systemic toxicity. These results highlight RGD-Lipo@GOx's potential as a nanotherapeutic platform that disrupts TNBC's metabolic and immune evasion mechanisms. Its high efficacy and safety suggest potential for clinical translation, particularly in combination with immunotherapies, and applicability to other glycolysis-driven cancers, advancing nanomedicine for precision oncology.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102889"},"PeriodicalIF":4.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer metastasis is the spread of cancerous cells through the circulatory system to distant organs. Existing in vitro models remain insufficient to faithfully reproduce the metastatic process. Multi-Organ-on-Chip (multi-OoC) platforms allow the integration of complex tissue models. Here, we propose a microplatform that recapitulates breast cancer (BC) migration to the liver, considering an endothelial barrier (EB) and immune cell interactions. Tissue micromodels were created using agarose multi-wells, loaded into the microplatform, and separated by different types of barriers: (i) collagen type I, (ii) cell culture medium, (iii) immune (Jurkat) cells, (iv) a microvessel, and (v) a microvessel perfused with Jurkat cells. Spatial arrangement of cells, their morphology, and viability were imaged using fluorescence microscopy over 10-day experiments. Quantitative data such as Feret Diameter, relative Raw Integrated Density (ID) and migration distance of tumor cells (GFP-MDA-MB-231) were evaluated. The concentrations of metastatic agents (interleukin-6 (IL-6), and interleukin-11 (IL-11)) were determined using ELISA. The potential of a microplatform in drug screening was preliminarily assessed with the use of Doxorubicin (Dox) over a 7-day experiment. Changes in Feret diameter and ID indicated a gradual disintegration of the BC micromodel. BC cells migrated toward the liver micromodel through a barrier formed in the central microchannel. An EB was impenetrable for GFP-MDA-MB-231, whereas Jurkat cells promoted the migration of BC cells. Dox induced transient inflammation and suppressed IL-11-dependent pro-metastatic signaling, consistent with its dual cytotoxic and immunomodulatory roles.
癌症转移是指癌细胞通过循环系统向远处器官扩散。现有的体外模型仍不足以忠实地再现转移过程。多器官芯片（multi-OoC）平台允许复杂组织模型的集成。在这里，我们提出了一个微平台，概述乳腺癌（BC）迁移到肝脏，考虑到内皮屏障（EB）和免疫细胞相互作用。使用琼脂糖多孔创建组织微模型，将其加载到微平台中，并通过不同类型的屏障分离：(i) i型胶原蛋白，（ii）细胞培养基，（iii）免疫（Jurkat）细胞，（iv）微血管，(v)灌注Jurkat细胞的微血管。在10天的实验中，使用荧光显微镜对细胞的空间排列、形态和活力进行成像。对肿瘤细胞的Feret Diameter、相对Raw Integrated Density （ID）和迁移距离（GFP-MDA-MB-231）等定量数据进行评价。采用酶联免疫吸附法（ELISA）检测转移物白介素-6 （IL-6）、白介素-11 （IL-11）的浓度。通过使用阿霉素（Dox）进行为期7天的实验，初步评估了微平台在药物筛选中的潜力。Feret直径和ID的变化表明BC微模型逐渐解体。BC细胞通过中央微通道形成的屏障向肝脏微模型迁移。GFP-MDA-MB-231无法穿透EB，而Jurkat细胞促进BC细胞的迁移。Dox诱导短暂性炎症并抑制il -11依赖的促转移信号，这与它的双重细胞毒性和免疫调节作用一致。
{"title":"Multi-Organ-on-Chip approach to exploring breast cancer liver metastases concerning the endothelial barrier and the influence of immune cells","authors":"Joanna Konopka , Joanna Roszczyk , Elżbieta Jastrzębska , Agnieszka Żuchowska","doi":"10.1016/j.nano.2025.102890","DOIUrl":"10.1016/j.nano.2025.102890","url":null,"abstract":"<div><div>Cancer metastasis is the spread of cancerous cells through the circulatory system to distant organs. Existing <em>in vitro</em> models remain insufficient to faithfully reproduce the metastatic process. Multi-Organ-on-Chip (multi-OoC) platforms allow the integration of complex tissue models. Here, we propose a microplatform that recapitulates breast cancer (BC) migration to the liver, considering an endothelial barrier (EB) and immune cell interactions. Tissue micromodels were created using agarose multi-wells, loaded into the microplatform, and separated by different types of barriers: (i) collagen type I, (ii) cell culture medium, (iii) immune (Jurkat) cells, (iv) a microvessel, and (v) a microvessel perfused with Jurkat cells. Spatial arrangement of cells, their morphology, and viability were imaged using fluorescence microscopy over 10-day experiments. Quantitative data such as Feret Diameter, relative Raw Integrated Density (ID) and migration distance of tumor cells (GFP-MDA-MB-231) were evaluated. The concentrations of metastatic agents (interleukin-6 (IL-6), and interleukin-11 (IL-11)) were determined using ELISA. The potential of a microplatform in drug screening was preliminarily assessed with the use of Doxorubicin (Dox) over a 7-day experiment. Changes in Feret diameter and ID indicated a gradual disintegration of the BC micromodel. BC cells migrated toward the liver micromodel through a barrier formed in the central microchannel. An EB was impenetrable for GFP-MDA-MB-231, whereas Jurkat cells promoted the migration of BC cells. Dox induced transient inflammation and suppressed IL-11-dependent pro-metastatic signaling, consistent with its dual cytotoxic and immunomodulatory roles.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102890"},"PeriodicalIF":4.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07DOI: 10.1016/j.nano.2025.102886
Jun Liu , Xiaoyu Hu , Qingrong Wang , Qiongkun Hu , Guanghao Yu , Yu Zhao , Liwei Gu , Jianying Shen , Qinghe Zhao , Feng Sui , Jingjing Zhu , Hai Ma
Limited therapeutic efficacy and significant toxicity consistently restrict the clinical development of chemotherapeutic drugs. To address these limitations, we engineered a multifunctional TAF-BP-DOX nanoplatform through the strategic combination of BP, doxorubicin, and a metal-polyphenol network (TAF). This rationally designed system exhibits dual responsiveness to tumor microenvironment characteristics, specifically acidic pH and elevated H2O2 levels. Upon NIR irradiation, the platform orchestrates a synergistic combination of chemotherapy, chemodynamic therapy, and photodynamic therapy, demonstrating markedly enhanced anti-hepatoma activity in both cellular and animal models compared to monotherapy approaches using either free DOX or TAF-DOX. Importantly, comprehensive evaluations revealed that the TAF-BP-DOX system not only improves therapeutic outcomes but also substantially mitigates the cardiotoxicity typically associated with DOX treatment. These collective findings position TAF-BP-DOX as a highly promising nanotherapeutic platform.
{"title":"Black phosphorus-based drug nanocarrier for synergetic chemo-, chemo-dynamic, and photo-dynamic therapy of liver cancer","authors":"Jun Liu , Xiaoyu Hu , Qingrong Wang , Qiongkun Hu , Guanghao Yu , Yu Zhao , Liwei Gu , Jianying Shen , Qinghe Zhao , Feng Sui , Jingjing Zhu , Hai Ma","doi":"10.1016/j.nano.2025.102886","DOIUrl":"10.1016/j.nano.2025.102886","url":null,"abstract":"<div><div>Limited therapeutic efficacy and significant toxicity consistently restrict the clinical development of chemotherapeutic drugs. To address these limitations, we engineered a multifunctional TAF-BP-DOX nanoplatform through the strategic combination of BP, doxorubicin, and a metal-polyphenol network (TAF). This rationally designed system exhibits dual responsiveness to tumor microenvironment characteristics, specifically acidic pH and elevated H<sub>2</sub>O<sub>2</sub> levels. Upon NIR irradiation, the platform orchestrates a synergistic combination of chemotherapy, chemodynamic therapy, and photodynamic therapy, demonstrating markedly enhanced anti-hepatoma activity in both cellular and animal models compared to monotherapy approaches using either free DOX or TAF-DOX. Importantly, comprehensive evaluations revealed that the TAF-BP-DOX system not only improves therapeutic outcomes but also substantially mitigates the cardiotoxicity typically associated with DOX treatment. These collective findings position TAF-BP-DOX as a highly promising nanotherapeutic platform.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102886"},"PeriodicalIF":4.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.nano.2025.102887
Marilène Bolduc , Philippe Saint-Louis , Damien Carignan , Caroline Garneau , Yann Breton , Martin Pelletier , Anne Rancourt , Masahiko S. Satoh , Sachiko Sato , Mégan Gilbert , Henintsoa Rabezanahary , Mariana Baz , Isabelle Dubuc , Louis Flamand , Denis Leclerc
Toll-like receptor (TLR) 7/8 agonists, such as imidazoquinoline derivatives (IMDs), hold great potential as immune modulators that can boost innate antiviral and anticancer immunity. However, significant challenges persist in achieving sufficient efficacy while minimizing toxic side effects. To date, only imiquimod (IMQ) has received FDA approval, and its use is restricted to topical applications. Therefore, there is a significant need for novel and safe TLR 7/8 agonists. In response to this, we developed a new generation of TLR7/8 agonist, the PapMV nanoparticle (PapMV nano). IMDs and PapMV nano are both innate immune system-activating drugs that have demonstrated antiviral and anticancer activities, but they differ significantly in three key aspects: (1) composition (proteins and ssRNA for PapMV nano vs. synthetic molecules for IMDs), (2) structure (large nanoparticles vs. small molecules), and (3) the mechanism of cell entry (internalization for PapMV nano vs. cell diffusion for IMDs). To compare how immune cells react to these two types of drug products, we studied cell motility, cell metabolism, and the induction of apoptosis in human monocyte-derived macrophages (hMDMs). Our data reveal that PapMV nano enhances motility and mitochondrial respiration while decreasing glycolysis, whereas IMDs have no impact on motility and mitochondrial respiration but increase glycolysis. PapMV nano is also the only agonist that does not induce apoptosis. Although the cellular responses to these two types of agonists differ strikingly, both are capable of eliciting antiviral immunity. We confirmed this potential for PapMV nano by demonstrating its capacity to prevent SARS-CoV-2 infection, supporting its utilization as a safe and effective immune modulator, capable of providing broad protection against respiratory viruses.
{"title":"PapMV nanoparticles: A novel pathway to SARS-CoV-2 protection, distinct from Imidazoquinolines","authors":"Marilène Bolduc , Philippe Saint-Louis , Damien Carignan , Caroline Garneau , Yann Breton , Martin Pelletier , Anne Rancourt , Masahiko S. Satoh , Sachiko Sato , Mégan Gilbert , Henintsoa Rabezanahary , Mariana Baz , Isabelle Dubuc , Louis Flamand , Denis Leclerc","doi":"10.1016/j.nano.2025.102887","DOIUrl":"10.1016/j.nano.2025.102887","url":null,"abstract":"<div><div>Toll-like receptor (TLR) 7/8 agonists, such as imidazoquinoline derivatives (IMDs), hold great potential as immune modulators that can boost innate antiviral and anticancer immunity. However, significant challenges persist in achieving sufficient efficacy while minimizing toxic side effects. To date, only imiquimod (IMQ) has received FDA approval, and its use is restricted to topical applications. Therefore, there is a significant need for novel and safe TLR 7/8 agonists. In response to this, we developed a new generation of TLR7/8 agonist, the PapMV nanoparticle (PapMV nano). IMDs and PapMV nano are both innate immune system-activating drugs that have demonstrated antiviral and anticancer activities, but they differ significantly in three key aspects: (1) composition (proteins and ssRNA for PapMV nano vs. synthetic molecules for IMDs), (2) structure (large nanoparticles vs. small molecules), and (3) the mechanism of cell entry (internalization for PapMV nano vs. cell diffusion for IMDs). To compare how immune cells react to these two types of drug products, we studied cell motility, cell metabolism, and the induction of apoptosis in human monocyte-derived macrophages (hMDMs). Our data reveal that PapMV nano enhances motility and mitochondrial respiration while decreasing glycolysis, whereas IMDs have no impact on motility and mitochondrial respiration but increase glycolysis. PapMV nano is also the only agonist that does not induce apoptosis. Although the cellular responses to these two types of agonists differ strikingly, both are capable of eliciting antiviral immunity. We confirmed this potential for PapMV nano by demonstrating its capacity to prevent SARS-CoV-2 infection, supporting its utilization as a safe and effective immune modulator, capable of providing broad protection against respiratory viruses.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102887"},"PeriodicalIF":4.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.nano.2025.102885
Xin Wei , Gang Zhao , Xiaoke Xu , Zhenshan Jia , Devendra Kumar , Evan Glissmeyer , Daniel Tran , Haochen Jiang , Sumbal Talib , Ningrong Chen , Zhulian Wang , Yazen Alnouti , Steven R. Goldring , Dong Wang
Intraarticular (IA) administration of ProGel-Dex was previously found to provide sustained joint pain relief with excellent safety in arthritis animal models. To explore ProGel-Dex’ working mechanisms, we conducted a comprehensive pharmacokinetics/biodistribution (PK/BD) study of IA ProGel-Dex and the free Dex released in an osteoarthritis mouse model. An initial “burst” release and distribution of ProGel-Dex was observed in all organs/tissues post IA administration. The higher-than-1.5 AUCinf_obs/AUCall ratios for both ProGel-Dex and free Dex support their long-term presence within the DMM joint beyond the experimental endpoint. The overall systemic organ/tissue exposures to ProGel-Dex and free Dex released were found to be much lower than those detected within the OA joint with IA ProGel-Dex. Together, these data support that the potent and long-sustained OA joint pain relief and the excellent safety of IA ProGel-Dex can be attributed to its prolonged retention in OA joint and the pathology-driven local activation.
{"title":"Pharmacokinetic and biodistribution (PK/BD) study of ProGel-Dex, a thermoresponsive dexamethasone prodrug for sustained joint pain relief in a mouse model of osteoarthritis","authors":"Xin Wei , Gang Zhao , Xiaoke Xu , Zhenshan Jia , Devendra Kumar , Evan Glissmeyer , Daniel Tran , Haochen Jiang , Sumbal Talib , Ningrong Chen , Zhulian Wang , Yazen Alnouti , Steven R. Goldring , Dong Wang","doi":"10.1016/j.nano.2025.102885","DOIUrl":"10.1016/j.nano.2025.102885","url":null,"abstract":"<div><div>Intraarticular (IA) administration of ProGel-Dex was previously found to provide sustained joint pain relief with excellent safety in arthritis animal models. To explore ProGel-Dex’ working mechanisms, we conducted a comprehensive pharmacokinetics/biodistribution (PK/BD) study of IA ProGel-Dex and the free Dex released in an osteoarthritis mouse model. An initial “burst” release and distribution of ProGel-Dex was observed in all organs/tissues post IA administration. The higher-than-1.5 AUC<sub>inf_obs</sub>/AUC<sub>all</sub> ratios for both ProGel-Dex and free Dex support their long-term presence within the DMM joint beyond the experimental endpoint. The overall systemic organ/tissue exposures to ProGel-Dex and free Dex released were found to be much lower than those detected within the OA joint with IA ProGel-Dex. Together, these data support that the potent and long-sustained OA joint pain relief and the excellent safety of IA ProGel-Dex can be attributed to its prolonged retention in OA joint and the pathology-driven local activation.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102885"},"PeriodicalIF":4.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.nano.2025.102884
Xinghan Zhang, Yuxin Liang, Francesco Zonta, Jeong Hyeon Park
Development of a transdermal drug delivery system must overcome the limited efficacy and reliability of current skin penetration methods. This study examined whether synthetic chromatin conjugated with the cell-penetrating peptide gH625 could traverse the epidermal barrier while maintaining cargo bioactivity. gH625-linked histone H2A assembled into chromatin was used to deliver DNA and peptides without penetration enhancers. gH625–chromatin increased cellular penetration by 150% compared with wild-type chromatin. Ex vivo porcine and in vivo mouse skin models demonstrated enhanced penetration depth up to 242 μm within 24 h, with signals confined to the dermis, indicating safe localized delivery. Epidermal growth factor (EGF) displayed at the histone H2B C-terminus maintained activity equivalent to free EGF, promoting cell growth, elevated COL1A1 secretion, and accelerated wound closure. These findings establish a chromatin-based nanoplatform for non-invasive transdermal delivery of bioactive macromolecules, filling a key gap in skin-targeted biotherapeutic delivery.
{"title":"Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide","authors":"Xinghan Zhang, Yuxin Liang, Francesco Zonta, Jeong Hyeon Park","doi":"10.1016/j.nano.2025.102884","DOIUrl":"10.1016/j.nano.2025.102884","url":null,"abstract":"<div><div>Development of a transdermal drug delivery system must overcome the limited efficacy and reliability of current skin penetration methods. This study examined whether synthetic chromatin conjugated with the cell-penetrating peptide gH625 could traverse the epidermal barrier while maintaining cargo bioactivity. gH625-linked histone H2A assembled into chromatin was used to deliver DNA and peptides without penetration enhancers. gH625–chromatin increased cellular penetration by 150% compared with wild-type chromatin. Ex vivo porcine and in vivo mouse skin models demonstrated enhanced penetration depth up to 242 μm within 24 h, with signals confined to the dermis, indicating safe localized delivery. Epidermal growth factor (EGF) displayed at the histone H2B C-terminus maintained activity equivalent to free EGF, promoting cell growth, elevated COL1A1 secretion, and accelerated wound closure. These findings establish a chromatin-based nanoplatform for non-invasive transdermal delivery of bioactive macromolecules, filling a key gap in skin-targeted biotherapeutic delivery.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102884"},"PeriodicalIF":4.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.nano.2025.102882
Esra Maltas Cagil , Lola Yakhshilikova , Mustafa Ersoz
Mebeverine (MBV) is a clinically approved antispasmodic agent indicated for irritable bowel syndrome (IBS) that functions via direct calcium channel inhibition in gastrointestinal smooth muscle, alleviating spasmodic pain without central anticholinergic effects. Optimal oral delivery mandates protection from gastric acidity (pH ~1.5–3.0) and targeted release in the small intestine (pH ~6.0–7.4) for prompt onset and sustained action. Here, we report a comparative evaluation of tartaric acid–iron(III) metal–organic frameworks (TF-MOFs) functionalized with globulin (TF-GLB) or human serum albumin (TF-HSA), loaded with MBV. TF-GLB-MBV released a higher amount of MBV at 7.4 and 9.0, suggesting unsuitability for neutral and basic environments with a concentration of 2.06 mg (12.73 %) and 3.67 mg (22.69 %) at first 15 min, respectively. For TF-HSA-MBV, the maximum MBV release amounts were 3.58 mg (5.22 %) and 0.9 mg (21.20 %), respectively. This comparative kinetic modeling study reveals that TF-HSA-MBV performs optimally in acidic and alkaline environments, following Higuchi diffusion-based release. Meanwhile, TF-GLB-MBV is more suitable for mildly acidic pH, exhibiting Case II transport, suggesting erosion- or swelling-controlled release—ideal for upper intestinal targeting. However, neither formulation performed optimally at physiological pH (7.4), which may require further formulation optimization. These findings support TF-GLB as a promising oral delivery system for IBS.
{"title":"Smart bioconjugated MOFs for targeted drug delivery: Albumin and globulin effects on mebeverine release dynamics","authors":"Esra Maltas Cagil , Lola Yakhshilikova , Mustafa Ersoz","doi":"10.1016/j.nano.2025.102882","DOIUrl":"10.1016/j.nano.2025.102882","url":null,"abstract":"<div><div>Mebeverine (MBV) is a clinically approved antispasmodic agent indicated for irritable bowel syndrome (IBS) that functions via direct calcium channel inhibition in gastrointestinal smooth muscle, alleviating spasmodic pain without central anticholinergic effects. Optimal oral delivery mandates protection from gastric acidity (pH ~1.5–3.0) and targeted release in the small intestine (pH ~6.0–7.4) for prompt onset and sustained action. Here, we report a comparative evaluation of tartaric acid–iron(III) metal–organic frameworks (TF-MOFs) functionalized with globulin (TF-GLB) or human serum albumin (TF-HSA), loaded with MBV. TF-GLB-MBV released a higher amount of MBV at 7.4 and 9.0, suggesting unsuitability for neutral and basic environments with a concentration of 2.06 mg (12.73 %) and 3.67 mg (22.69 %) at first 15 min, respectively. For TF-HSA-MBV, the maximum MBV release amounts were 3.58 mg (5.22 %) and 0.9 mg (21.20 %), respectively. This comparative kinetic modeling study reveals that TF-HSA-MBV performs optimally in acidic and alkaline environments, following Higuchi diffusion-based release. Meanwhile, TF-GLB-MBV is more suitable for mildly acidic pH, exhibiting Case II transport, suggesting erosion- or swelling-controlled release—ideal for upper intestinal targeting. However, neither formulation performed optimally at physiological pH (7.4), which may require further formulation optimization. These findings support TF-GLB as a promising oral delivery system for IBS.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102882"},"PeriodicalIF":4.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.nano.2025.102877
Oluwatobi H. Babayemi , Corinne Fotso , Sauradip Chaudhuri , Lindsey K. Sablatura , Cassandra Baker , Fred Christian Velasquez , Janelle Morton , Eva Sevick-Muraca , Rachael W. Sirianni
Intrathecal drug delivery refers to the direct administration of compounds to cerebrospinal fluid (CSF), which can enhance delivery to the central nervous system (CNS) while minimizing peripheral exposure. Our prior work demonstrated that 100 nm, solid polystyrene nanoparticles surface modified with poly(ethylene glycol) (PEG) distribute within the CNS after intrathecal administration via the cisterna magna route (IT-CM). Here, we focus on comparing nanoparticle fate following administration to IT CM versus lumbar (IT-L) access points. We utilized dynamic a variety of imaging techniques to track the movement of model, 64Cu-radiolabeled, fluorescent nanoparticles, hypothesizing that the IT-CM route would enable greater brain-localized delivery of nanoparticles when compared with the IT-L route. Spatiotemporal patterns of nanoparticle distribution and clearance were studied through a combination of quantitative positron emission tomography/computer tomography (PET/CT), fluorescent imaging (confocal microscopy), and biodistribution experiments (liquid scintillation counting). These studies revealed that: (1) the IT-CM route yielded greater brain-wide nanoparticle delivery while the IT-L route yielded greater spinal delivery, (2) the IT-CM route resulted in sustained retention of nanoparticles within the CNS and proximal lymphatics while the IT-L route resulted in higher nanoparticle clearance to peripheral organs, and (3) both the IT-CM and IT-L routes resulted in detectable though incomplete parenchymal delivery of nanoparticles, with the majority of signal remaining confined to the subarachnoid space. These findings underscore the pivotal role of intrathecal location in influencing nanoparticle biodistribution and clearance pathways within the CNS, identifying access point as an important design parameter when optimizing nanomedicine for intrathecal drug delivery.
{"title":"Nanoparticle distribution in the central nervous system following intrathecal administration: A multi-modal analysis of lumbar versus cisterna magna routes","authors":"Oluwatobi H. Babayemi , Corinne Fotso , Sauradip Chaudhuri , Lindsey K. Sablatura , Cassandra Baker , Fred Christian Velasquez , Janelle Morton , Eva Sevick-Muraca , Rachael W. Sirianni","doi":"10.1016/j.nano.2025.102877","DOIUrl":"10.1016/j.nano.2025.102877","url":null,"abstract":"<div><div>Intrathecal drug delivery refers to the direct administration of compounds to cerebrospinal fluid (CSF), which can enhance delivery to the central nervous system (CNS) while minimizing peripheral exposure. Our prior work demonstrated that 100 nm, solid polystyrene nanoparticles surface modified with poly(ethylene glycol) (PEG) distribute within the CNS after intrathecal administration via the cisterna magna route (IT-CM). Here, we focus on comparing nanoparticle fate following administration to IT CM versus lumbar (IT-L) access points. We utilized dynamic a variety of imaging techniques to track the movement of model, <sup>64</sup>Cu-radiolabeled, fluorescent nanoparticles, hypothesizing that the IT-CM route would enable greater brain-localized delivery of nanoparticles when compared with the IT-L route. Spatiotemporal patterns of nanoparticle distribution and clearance were studied through a combination of quantitative positron emission tomography/computer tomography (PET/CT), fluorescent imaging (confocal microscopy), and biodistribution experiments (liquid scintillation counting). These studies revealed that: (1) the IT-CM route yielded greater brain-wide nanoparticle delivery while the IT-L route yielded greater spinal delivery, (2) the IT-CM route resulted in sustained retention of nanoparticles within the CNS and proximal lymphatics while the IT-L route resulted in higher nanoparticle clearance to peripheral organs, and (3) both the IT-CM and IT-L routes resulted in detectable though incomplete parenchymal delivery of nanoparticles, with the majority of signal remaining confined to the subarachnoid space. These findings underscore the pivotal role of intrathecal location in influencing nanoparticle biodistribution and clearance pathways within the CNS, identifying access point as an important design parameter when optimizing nanomedicine for intrathecal drug delivery.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102877"},"PeriodicalIF":4.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-23DOI: 10.1016/j.nano.2025.102881
Ridha.M. Lefta , Samer Saleem Alshkarchy , Thekra F. Ali , Majid S. Jabir , Wesam R. Kadhum
Prostate cancer (PCa) remains a major clinical challenge due to limited treatment efficacy, frequent resistance, and high recurrence rates. Given the susceptibility of cancer cells to oxidative stress, reactive oxygen species (ROS)-based strategies offer promising therapeutic potential. Photothermal therapy (PTT) and sonodynamic therapy (SDT) are emerging minimally invasive modalities that exploit nanotechnology to induce localized ROS generation. This review highlights recent advances in ROS-mediated PTT and SDT for PCa, emphasizing nanomaterial design and functionalization to enhance targeting precision, drug delivery, and overcome tumor hypoxia. Combining PTT and SDT with chemotherapy, radiotherapy, or immunotherapy produces synergistic effects, potentially overcoming resistance and eliciting systemic antitumor immunity. Preclinical studies demonstrate effective tumor eradication and immune activation with minimal toxicity, suggesting promise for clinical translation. However, human clinical trials remain scarce, and further translational research is needed before these nanotechnology-based approaches can be integrated into standard PCa treatment.
{"title":"Targeting prostate cancer through reactive oxygen species: Advances in photothermal and sonodynamic therapies","authors":"Ridha.M. Lefta , Samer Saleem Alshkarchy , Thekra F. Ali , Majid S. Jabir , Wesam R. Kadhum","doi":"10.1016/j.nano.2025.102881","DOIUrl":"10.1016/j.nano.2025.102881","url":null,"abstract":"<div><div>Prostate cancer (PCa) remains a major clinical challenge due to limited treatment efficacy, frequent resistance, and high recurrence rates. Given the susceptibility of cancer cells to oxidative stress, reactive oxygen species (ROS)-based strategies offer promising therapeutic potential. Photothermal therapy (PTT) and sonodynamic therapy (SDT) are emerging minimally invasive modalities that exploit nanotechnology to induce localized ROS generation. This review highlights recent advances in ROS-mediated PTT and SDT for PCa, emphasizing nanomaterial design and functionalization to enhance targeting precision, drug delivery, and overcome tumor hypoxia. Combining PTT and SDT with chemotherapy, radiotherapy, or immunotherapy produces synergistic effects, potentially overcoming resistance and eliciting systemic antitumor immunity. Preclinical studies demonstrate effective tumor eradication and immune activation with minimal toxicity, suggesting promise for clinical translation. However, human clinical trials remain scarce, and further translational research is needed before these nanotechnology-based approaches can be integrated into standard PCa treatment.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102881"},"PeriodicalIF":4.6,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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