Pub Date : 2026-03-13eCollection Date: 2026-01-01DOI: 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.
{"title":"Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention.","authors":"Jianwen Zhang, Minjie Zhang, Xiaoru Ren, Mengying Li, Yiwen Zhu, Dan Shou, Yang Zhang","doi":"10.2147/IJN.S582197","DOIUrl":"https://doi.org/10.2147/IJN.S582197","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"582197"},"PeriodicalIF":6.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"An Injectable Photothermal Responsive Liposome Hydrogel Co-Loaded with Bufalin, Apatinib, and IR820 for Inhibiting Postoperative Recurrence of Colon Cancer.","authors":"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","doi":"10.2147/IJN.S575430","DOIUrl":"https://doi.org/10.2147/IJN.S575430","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"575430"},"PeriodicalIF":6.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12eCollection Date: 2026-01-01DOI: 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.
{"title":"Nanotechnology-Enabled Diagnosis and Treatment of Hepatocellular Carcinoma: Theranostics, Combination Regimens, and Translation.","authors":"Siyao Wang, Yang Wu, Miao Yuan, Jing Zheng, Chaoran Wang, Jiarong Wang, Yifan Zheng, Qiaoyun Yang, Mengran Xu, Baiqi Wang","doi":"10.2147/IJN.S581911","DOIUrl":"https://doi.org/10.2147/IJN.S581911","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"581911"},"PeriodicalIF":6.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11eCollection Date: 2026-01-01DOI: 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.
{"title":"Pearl Powder Fluorescent Carbon Dots Alleviate Neuroinflammation in Cerebral Ischemia/Reperfusion Through Suppression of Anxa2/NF-κB Signaling Pathway.","authors":"Pongsigeraxi Borjigin, Caixia Deng, Rilaga Su, Juan Li, Ying Ying, Yingsong Chen, Tegexibaiyin Wang","doi":"10.2147/IJN.S567974","DOIUrl":"https://doi.org/10.2147/IJN.S567974","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"567974"},"PeriodicalIF":6.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12991296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"The Role of Bacterial Outer Membrane Vesicles in Tumor Development: Facts, Potential Applications and Future Perspectives.","authors":"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","doi":"10.2147/IJN.S582600","DOIUrl":"https://doi.org/10.2147/IJN.S582600","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"582600"},"PeriodicalIF":6.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Enhancement of Psoriasis Treatment by Phellodendri Chinensis Cortex Carbon Dots (PCC-CDs) Through Modulation of the HMGB1/TLR4/MAPK/NF-κB Pathway.","authors":"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","doi":"10.2147/IJN.S578399","DOIUrl":"https://doi.org/10.2147/IJN.S578399","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"578399"},"PeriodicalIF":6.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10eCollection Date: 2026-01-01DOI: 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.
{"title":"Nanoparticles in the Treatment of Renal Fibrosis.","authors":"Ying Wu, Wen Zhang, Li'ou Zhu, Lili Liu","doi":"10.2147/IJN.S585576","DOIUrl":"https://doi.org/10.2147/IJN.S585576","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"585576"},"PeriodicalIF":6.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Design Evolution of Curcumin-Loaded Nanostructured Lipid Carriers: Formulation Strategies, Functional Modifications, and Mechanistic-Translational Perspectives.","authors":"Ikra Nurohman, Cecep Suhandi, Anis Yohana Chaerunisaa, Gofarana Wilar, Garnadi Jafar, Sriwidodo Sriwidodo","doi":"10.2147/IJN.S586727","DOIUrl":"https://doi.org/10.2147/IJN.S586727","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"586727"},"PeriodicalIF":6.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10eCollection Date: 2026-01-01DOI: 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.
{"title":"Intratracheal Administration of pH-Responsive Nanomicelles: A More Effective Strategy for Enhanced Intracellular Drug Delivery in Lung Cancer Treatment.","authors":"Luting Lin, Guowei Wang, Jie Zhang, Jingming Luo, Xudong Fan, Jianqing Gao, Xinjun Cai","doi":"10.2147/IJN.S555824","DOIUrl":"https://doi.org/10.2147/IJN.S555824","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"555824"},"PeriodicalIF":6.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"From Barrier to Gateway: Nanomaterials Reshaping the Tumor Microenvironment for Therapy.","authors":"Mina Xie, Wanyu Sun, Dongping Hu, Lu Liu, Caiwen Han, Wenhan Liu, Lede Liu, Xiaojiang Bao, Weisheng Zhang, Xiangyong Hao, Yongqiang Zhou","doi":"10.2147/IJN.S573490","DOIUrl":"https://doi.org/10.2147/IJN.S573490","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"573490"},"PeriodicalIF":6.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}