Journal of Nanobiotechnology最新文献

{"title":"Copper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming.","authors":"Yang Chen, Hailong Tian, Xiaodian Zhang, Edouard C Nice, Canhua Huang, Haiyuan Zhang, Shaojiang Zheng","doi":"10.1186/s12951-024-03059-2","DOIUrl":"10.1186/s12951-024-03059-2","url":null,"abstract":"<p><p>Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu²⁺ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"801"},"PeriodicalIF":10.6,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating electrospun aligned fiber scaffolds with bovine serum albumin-basic fibroblast growth factor nanoparticles to promote tendon regeneration.","authors":"Yuwan Li, Zhen Ge, Ziming Liu, Longfei Li, Jian Song, Hongde Wang, Feng Tian, Pengfei Lei, Long Li, Jiajia Xue","doi":"10.1186/s12951-024-03022-1","DOIUrl":"10.1186/s12951-024-03022-1","url":null,"abstract":"<p><strong>Background: </strong>Electrospun nanofiber scaffolds have been widely used in tissue engineering because they can mimic extracellular matrix-like structures and offer advantages including high porosity, large specific surface area, and customizable structure. In this study, we prepared scaffolds composed of aligned and random electrospun polycaprolactone (PCL) nanofibers capable of delivering basic fibroblast growth factor (bFGF) in a sustained manner for repairing damaged tendons.</p><p><strong>Results: </strong>Aligned and random PCL fiber scaffolds containing bFGF-loaded bovine serum albumin (BSA) nanoparticles (BSA-bFGF NPs, diameter 146 ± 32 nm) were fabricated, respectively. To validate the viability of bFGF-loaded aligned PCL nanofiber scaffold (aPCL + bFGF group) in tendon tissue engineering, we assessed the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage and the in vivo regeneration of tendons using a rat Achilles tendon defect model. The encapsulated bFGF could be delivered in a sustained manner in vitro. The aPCL + bFGF scaffold promoted the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage. In the repair of a rat Achilles tendon defect model, the aPCL + bFGF group showed a better repair effect. The scaffold offers a promising substrate for the regeneration of tendon tissue.</p><p><strong>Conclusions: </strong>The aligned and random PCL fiber scaffolds containing bFGF nanoparticles were successfully prepared, and their physical and chemical properties were characterized. The aPCL + bFGF scaffold could promote the expression of the related genes and proteins of tendon-forming, facilitating tendon differentiation. In the rat Achilles tendon defect experiments, the aPCL + bFGF exhibited excellent tendon regeneration effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"799"},"PeriodicalIF":10.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of PCBP2 in regulating nanovesicles loaded with curcumin to mitigate neuroferroptosis in neural damage caused by heat stroke.","authors":"Fei Guo, Yizhan Wu, Guangjun Wang, Jiangwei Liu","doi":"10.1186/s12951-024-02889-4","DOIUrl":"10.1186/s12951-024-02889-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood-brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Initially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis. Evaluations included assessing the toxicity of NVs-CUR using the MTT assay, evaluating neuroprotection of NVs-CUR against H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-induced oxidative stress damage in PC12 cells, examining effects on cell morphology and quantity, and detecting ferroptosis-related markers through Western blot and transmission electron microscopy (TEM). Proteomic analysis was conducted on PC12 cells treated with NVs (n = 3) and NVs-CUR (n = 3) to identify downstream key factors. Subsequently, the expression of key factors was modulated, and rescue experiments were performed to validate the impact of NVs-CUR through the regulation of key factor expression. Furthermore, a mouse model of hypothalamic neural damage induced by heat stroke was established, where CUR, NVs-CUR, and ferroptosis inducer Erastin were administered to observe mouse survival rates, conduct nerve function deficit scoring, perform histological staining, and measure levels of inflammation and oxidative stress factors in hypothalamic tissue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;NVs-CUR was successfully prepared with excellent stability, serving as an advantageous drug delivery system that effectively targets brain injury sites or neurons both in vitro and in vivo. Subsequent in vitro cell experiments demonstrated the biocompatibility of NVs-CUR, showing superior protective effects against H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-induced PC12 cell damage and reduced ferroptosis compared to CUR. Moreover, in the mouse model of hypothalamic neural damage induced by heat stroke, NVs-CUR exhibited enhanced therapeutic effects. Proteomic analysis revealed that NVs-CUR exerted its effects through the regulation of key protein PCBP2; silencing PCBP2 reversed the protective effect of NVs-CUR on neural damage and its inhibition of ferroptosis. Additionally, NVs-CUR regulated solute carrier family 7 member 11 (SLC7A11) expression by PCBP2; overexpression of SLC7A11 reversed the promotion of neural damage and ferroptosis by silencing PCBP2. Animal experiments indicated that ferroptosis inducers reversed the improved survival and nerve function observed with NVs-CUR, silencing PCBP2 reversed the ameliorative effects of NVs-CUR on hypothalamic neural injury induced by heat stroke, and overexpression of SLC7A11 further reversed the adverse effects of silencing PCBP2 on hypothalamic neural injury induced by heat ","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"800"},"PeriodicalIF":10.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal-controllable ROS-responsive camptothecin nano-bomb for chemo/photo/immunotherapy in triple-negative breast cancer.","authors":"Wenjie Xu, Zhaokui Zeng, Yucheng Tang, Jingjing Tian, Xinyan Hao, Pengcheng Sun, Yanjin Peng, Tian Tian, Daxiong Xiang, Rongrong Wang, Chuanpin Chen, Junyong Wu","doi":"10.1186/s12951-024-03050-x","DOIUrl":"10.1186/s12951-024-03050-x","url":null,"abstract":"<p><p>Chemotherapy is still one of the major approaches in triple-negative breast cancer (TNBC) treatment. The development of new formulations for classic chemotherapeutic drugs remains interests in studies. Camptothecin (CPT) is powerful antitumor agents in TNBC treatment though its clinic applications are limited by its low water solubility and systemic toxicity. To prepare a spatiotemporal controllable CPT nano-formulation, we construct a ROS-responsive self-assembly nanoparticle by combining hydrophobic CPT and hydrophilic 5-floxuridine (FUDR). A ROS-sensitive thioketal (TK) linker is used to prepare CPT-TK-FUDR (CTF). Next, we introduced IR780-based phototherapy to elicit massive ROS regeneration due to the endogenous ROS is not sufficient. IR780 is modified with hyaluronic acid (HA) to prepare HA-modified IR780 (HAIR) for its biocompatibility and tumor targeting ability improvement. CTF and HAIR self-assemble to form an attractive nano-bomb (HAIR/CTF NPs). HA accurately guides the NPs to tumor sites via HA-receptor recognition on tumor cells. After internalization, overexpressed intracellular HAase in tumor cells disassembles the NPs to free the contents. Due to the presence of IR780 molecules, the scheduled irradiation of 808 nm laser induces massive reactive oxygen species (ROS) generation, which further result in the cleavage of TK linker for free drugs release. Additionally, ROS-mediated photodynamic therapy (PDT) and near-infrared laser-mediated photothermal therapy (PTT) synergistically worked to eradicate tumor cells. Then immunogenic cell death (ICD) was evoked by CPT and phototherapy to amplify antitumor immunity, thereby achieving primary and abscopal tumor inhibition. In conclusion, the HAIR/CTF nano-bomb realized spatiotemporal controllable drug release, exciting tumor eradication and attractive anti-metastasis efficacy via combination chemo/photo/immunotherapy, offering a valuable reference for the re-development of classic drug in future clinical practice.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"798"},"PeriodicalIF":10.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDGFR-α shRNA-polyplex for uveal melanoma treatment via EMT mediated vasculogenic mimicry interfering.","authors":"Jiahao Wang, Zhirong Chen, Peiyi Zhao, Yajia Wang, Jiang Chen, Quankui Lin","doi":"10.1186/s12951-024-03077-0","DOIUrl":"10.1186/s12951-024-03077-0","url":null,"abstract":"<p><p>Up to 50% of individuals with uveal melanoma (UM), a frequent cancer of the eye, pass away from metastases. One of the major challenges in treating UM is the role of receptor tyrosine kinases (RTKs), which mediate the epithelial-mesenchymal transition (EMT) of tumors. RTKs are involved in binding multiple growth factors, leading to angiogenesis and vasculogenic mimicry (VM) phenomena. Currently, most anti-angiogenic drugs have shown a tendency to increase the VM of tumors in clinical trials, resulting in limited efficacy. The existing gap in UM treatment lies in the lack of effective strategies to target RTK-mediated EMT and VM. While some approaches have been attempted, there is still a need for novel therapeutic interventions that can specifically interfere with these processes. This research employed the gene vector PEI-g-PEG to interfere with the platelet derived growth factor-alpha receptor (PDGFR-α)-mediated EMT process, thereby retarding the growth of UM. The cell experiments demonstrated that the gene polyplex exhibited favorable cell uptake and lysosome escape properties, effectively suppressing the expression of PDGFR-α protein and EMT marker proteins and the occurrence of VM phenomenon. In vivo animal studies also inhibited the growth of UM, and PAS assays showed that the treatment reduced the generation of VM in tumor tissue. This study broadens the application of PEI-g-PEG while interfering with the RTK-mediated tumor EMT process with the help of RNAi technology, providing a new idea for tumor reduction research.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"797"},"PeriodicalIF":10.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the molecular blueprint of SKP-SCs-mediated tissue engineering-enhanced neuroregeneration.","authors":"Hui Zhu, Ying Wang, Siyuan Xu, Yunjian Song, Yifan Li, Yiting Wang, Qiuwen Sun, Muyuan Tong, Tianyi Huang, Yulin Pan, Hongkui Wang, Xi Xu, Chengbin Xue","doi":"10.1186/s12951-024-03076-1","DOIUrl":"10.1186/s12951-024-03076-1","url":null,"abstract":"<p><p>Peripheral nerve injury poses a significant challenge to the nervous system's regenerative capacity. We previously described a novel approach to construct a chitosan/silk fibroin nerve graft with skin-derived precursor-induced Schwann cells (SKP-SCs). This graft has been shown to promote sciatic nerve regeneration and functional restoration to a level comparable to that achieved by autologous nerve grafts, as evidenced by behavioral, histological, and electrophysiological assessments. However, the underlying molecular mechanisms based on SKP-SCs mediated tissue engineering-aid regeneration remain elusive. In the present work, we systematically identified gene modules associated with the differentiation of SKPs into SCs by employing weighted gene co-expression network analysis (WGCNA). By integrating transcriptomic data from the regenerated nerve segment, we constructed a network that delineated the molecular signatures of TENG aid neuroregeneration. Subsequent quantitative PCR (qPCR) validation was performed to substantiate the WGCNA findings. Our WGCNA approach revealed a robust molecular landscape, highlighting hub genes pivotal for tissue engineering-aid regeneration. Notably, the upregulation of specific genes was observed to coincide with the acquisition of SC characteristics. The qPCR validation confirmed the expression patterns of these genes, underscoring their role in promoting neuroregeneration. The current study harnesses the power of WGCNA to elucidate the molecular blueprint governing tissue engineering-aid regeneration. The identified gene modules and validated targets offer novel insights into the cellular and molecular underpinnings of tissue engineering-augmented neuroregeneration. These findings pave the way for developing targeted therapeutics and advanced tissue engineering grafts to enhance peripheral nerve repair.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"796"},"PeriodicalIF":10.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural epigallocatechin-3-gallocarboxylate nanoformulation loaded doxorubicin to construct a novel and low cardiotoxicity chemotherapeutic drug for high-efficiency breast cancer therapy.","authors":"Ke Wang, Siqi Geng, Fang Wang, Baoru Fang, Huifeng Qian, Ying Li, Yiqing Zhou, Yanping Chen, Zhangsen Yu","doi":"10.1186/s12951-024-03069-0","DOIUrl":"10.1186/s12951-024-03069-0","url":null,"abstract":"<p><p>Anthracycline doxorubicin (DOX) remains the first-line chemotherapeutic drug for the efficient treatment of breast cancer, but its severe cardiotoxicity limits its long-term application in clinical tumor chemotherapy. Until now, the pathogenesis mechanism of DOX-induced cardiotoxicity (DIC) is still not fully understood. According to current studies, the oxidative stress caused by the imbalance of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and mitochondrial dysfunction in myocardial cells are closely related to DIC. Presently, the usual technology to solve the DIC problem is to use a multifunctional nanoplatform to load DOX and obtain a new medicinal agent, thereby enhancing the efficacy of chemotherapeutic drugs and reducing toxic side effects.Herein, the present investigation employed the Mannich condensation reaction, initiated by L-cysteine and (-)-epigallocatechin-3-gallocarboxylate (EGCG), to synthesize EGCG&Cys nanoformulation with both anti-tumor and anti-oxidant properties. The EGCG&Cys were then employed as the DOX carrier to construct a novel chemotherapeutic drug, EGCG&Cys(DOX), for high-efficiency breast cancer treatment. The tumor growth inhibition index of EGCG&Cys(DOX) in tumor-bearing mice was 12.56% superior to the DOX group with the same concentration. Meanwhile, the anti-oxidant properties of EGCG can effectively eliminate a large amount of free radicals produced by DOX and significantly alleviate DIC by improving mitochondrial functional pathways. Ultrasound echocardiography (UCG) showed that the mean LVEF and LEFS values in the 5 mg/kg DOX treatment group were significantly reduced by 54.4% and 63.4%, and the EGCG&Cys(DOX) group mice were consistent with those of the non-chemotherapy group. Moreover, electrocardiogram, serum biochemical indicators, and histopathological analysis results also demonstrate that the cardiotoxicity of EGCG&Cys(DOX) novel chemotherapy drugs is significantly reduced. Consequently, this study presents a new technology for preparing highly efficient and safe nano-chemotherapeutic drugs and an in-depth evaluation of the antitumor efficacy and safety of the synthesized novel drugs, which gave fresh life to the development of nanomedicine in the clinical treatment of breast cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"793"},"PeriodicalIF":10.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice.","authors":"Xiaomei Wang, Jinglin Tian, Ken-Tye Yong, Xuedan Zhu, Marie Chia-Mi Lin, Wenxiao Jiang, Jiefeng Li, Qijun Huang, Guimiao Lin","doi":"10.1186/s12951-024-02991-7","DOIUrl":"10.1186/s12951-024-02991-7","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"794"},"PeriodicalIF":10.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis.","authors":"Adrián Palencia-Campos, Laura Ruiz-Cañas, Marcelina Abal-Sanisidro, Juan Carlos López-Gil, Sandra Batres-Ramos, Sofia Mendes Saraiva, Balbino Yagüe, Diego Navarro, Sonia Alcalá, Juan A Rubiolo, Nadège Bidan, Laura Sánchez, Simona Mura, Patrick C Hermann, María de la Fuente, Bruno Sainz","doi":"10.1186/s12951-024-03010-5","DOIUrl":"10.1186/s12951-024-03010-5","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.</p><p><strong>Results: </strong>In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem's therapeutic effect in the context of human PDAC metastasis.</p><p><strong>Conclusions: </strong>The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"795"},"PeriodicalIF":10.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bright NIR-II emissive cyanine dye-loaded lipoprotein-mimicking nanoparticles for fluorescence imaging-guided and targeted NIR-II photothermal therapy of subcutaneous glioblastoma.","authors":"Haiyan Huang, Menlong Li, Jingsi Gu, Shubham Roy, Jian Jin, Ting Kuang, Yinghe Zhang, Genwen Hu, Bing Guo","doi":"10.1186/s12951-024-03074-3","DOIUrl":"10.1186/s12951-024-03074-3","url":null,"abstract":"<p><p>Cyanine dye-containing nanoparticles have widely been used in \"all-in-one\" NIR fluorescence imaging (FI)-guided photothermal therapy (PTT) because of their intrinsically large extinction coefficient and available physical and chemical modulation methods to tune absorption and emission wavelengths. The combination of good brightness and excellent tumor-targeting capacity is the key to realize efficient NIR-II FI-guided PTT. In this study, by covalently decorating NIR-II absorptive cyanine dyes with bulky AIE motify, we demonstrate how steric hindrance suppresses π-π stacking-induced fluorescence quenching and contributes to the good brightness of NIR-II FI of subcutaneous glioblastoma. The resulting cyanine dye (C₁₂-TPAE) is 5 times brighter than the original cyanine dye in the formulated liposomal nanoparticles and C₁₂-TPAE-AL has a high photothermal conversion efficiency of 62.4%, with good colloidal and light stability. Importantly, the ApoE peptide is absorbed on the liposomal surface, yielding lipoprotein-mimicking nanoparticles, which achieve active targeting of glioblastoma and efficient FI-guided PTT without tumor recurrence without any side effects on normal organs (heart, kidneys, liver, spleen, or lung). This research highlights a facile design route for bright NIR-II emissive and NIR-II photothermal cyanine dyes and indicates that cyanine dye-containing biomimetic theranostic nanoplatforms are promising candidates for future precision therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"788"},"PeriodicalIF":10.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}