首页 > 最新文献

Nanomedicine : nanotechnology, biology, and medicine最新文献

英文 中文
Functionalization and magnetonavigation of T-lymphocytes functionalized via nanocomposite capsules targeting with electromagnetic tweezers 利用电磁镊子对通过纳米复合胶囊靶向的 T 淋巴细胞进行功能化和磁导航。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-03-07 DOI: 10.1016/j.nano.2024.102742
Anatolii Abalymov PhD , Maxim A. Kurochkin PhD , Sergei German PhD , Aleksei Komlev MSc , Evgeny S. Vavaev MSc , Evgeny V. Lyubin PhD , Andrey A. Fedyanin DSc (Habilitation) , Dmitry Gorin DSc , Marina Novoselova PhD

Modification of T-lymphocytes, which are capable of paracellular transmigration is a promising trend in modern personalized medicine. However, the delivery of required concentrations of functionalized T-cells to the target tissues remains a problem. We describe a novel method to functionalize T-cells with magnetic nanocapsules and target them with electromagnetic tweezers. T-cells were modified with the following magnetic capsules: Parg/DEX (150 nm), BSA/TA (300 nm), and BSA/TA (500 nm). T-cells were magnetonavigated in a phantom blood vessel capillary in cultural medium and in whole blood. The permeability of tumor tissues to captured T-cells was analyzed by magnetic delivery of modified T-cells to spheroids formed from 4T1 breast cancer cells. The dynamics of T-cell motion under a magnetic field gradient in model environments were analyzed by particle image velocimetry. The magnetic properties of the nanocomposite capsules and magnetic T-cells were measured. The obtained results are promising for biomedical applications in cancer immunotherapy.

对 T 淋巴细胞进行改造,使其能够进行细胞旁转移,是现代个性化医疗的一个大有可为的趋势。然而,如何将所需浓度的功能化 T 细胞输送到靶组织仍是一个问题。我们介绍了一种用磁性纳米胶囊功能化 T 细胞并用电磁镊瞄准它们的新方法。我们用以下磁性胶囊修饰了 T 细胞:Parg/DEX(150 nm)、BSA/TA(300 nm)和 BSA/TA(500 nm)。T 细胞在培养基和全血中的模型血管毛细管中进行磁导航。通过将修饰的 T 细胞磁性输送到由 4T1 乳腺癌细胞形成的球形组织,分析了肿瘤组织对捕获的 T 细胞的渗透性。利用粒子图像测速仪分析了模型环境中磁场梯度下 T 细胞的运动动态。还测量了纳米复合胶囊和磁性 T 细胞的磁性能。研究结果有望应用于癌症免疫治疗的生物医学领域。
{"title":"Functionalization and magnetonavigation of T-lymphocytes functionalized via nanocomposite capsules targeting with electromagnetic tweezers","authors":"Anatolii Abalymov PhD ,&nbsp;Maxim A. Kurochkin PhD ,&nbsp;Sergei German PhD ,&nbsp;Aleksei Komlev MSc ,&nbsp;Evgeny S. Vavaev MSc ,&nbsp;Evgeny V. Lyubin PhD ,&nbsp;Andrey A. Fedyanin DSc (Habilitation) ,&nbsp;Dmitry Gorin DSc ,&nbsp;Marina Novoselova PhD","doi":"10.1016/j.nano.2024.102742","DOIUrl":"10.1016/j.nano.2024.102742","url":null,"abstract":"<div><p>Modification of T-lymphocytes, which are capable of paracellular transmigration is a promising trend in modern personalized medicine. However, the delivery of required concentrations of functionalized T-cells to the target tissues remains a problem. We describe a novel method to functionalize T-cells with magnetic nanocapsules and target them with electromagnetic tweezers. T-cells were modified with the following magnetic capsules: Parg/DEX (150 nm), BSA/TA (300 nm), and BSA/TA (500 nm). T-cells were magnetonavigated in a phantom blood vessel capillary in cultural medium and in whole blood. The permeability of tumor tissues to captured T-cells was analyzed by magnetic delivery of modified T-cells to spheroids formed from 4T1 breast cancer cells. The dynamics of T-cell motion under a magnetic field gradient in model environments were analyzed by particle image velocimetry. The magnetic properties of the nanocomposite capsules and magnetic T-cells were measured. The obtained results are promising for biomedical applications in cancer immunotherapy.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102742"},"PeriodicalIF":5.4,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068590","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}
引用次数: 0
M2-type macrophage-targeted delivery of IKKβ siRNA induces M2-to-M1 repolarization for CNV gene therapy M2型巨噬细胞靶向递送IKKβ siRNA可诱导M2-M1再极化,用于CNV基因治疗。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-03-06 DOI: 10.1016/j.nano.2024.102740
Yu Zhang MD , Baorui Chu MD , Qian Fan MD , Xian Song MD , Qian Xu MD , Yi Qu MD

Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis.

To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase β (IKKβ) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKβ siRNA-loaded liposome (siIKKβ-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKβ-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.

脉络膜新生血管(CNV)可导致黄斑区反复出血,严重损害患者的视力。在 CNV 的发病过程中,浸润的 M2 巨噬细胞在促进血管生成方面起着至关重要的作用。为了控制这种疾病,我们的研究利用基于 RNA 干扰(RNAi)的基因疗法将 CNV 病变中的 M2 巨噬细胞重编程为 M1 表型。我们合成了甘露糖修饰的 siRNA 脂质体,专门靶向 M2 巨噬细胞,抑制参与巨噬细胞极化的抑制性卡巴 B 激酶 β(IKKβ)基因,从而调节巨噬细胞的极化状态。在体外和体内,甘露糖修饰的 IKKβ siRNA 载体脂质体(siIKKβ-ML)已被证实能有效靶向 M2 巨噬细胞,使其重新极化为 M1 表型,并抑制 CNV 的进展。总之,我们的研究结果阐明,siIKKβ-ML 有可能通过重编程巨噬细胞表型来控制 CNV,为 CNV 的治疗提供了一条前景广阔的途径。
{"title":"M2-type macrophage-targeted delivery of IKKβ siRNA induces M2-to-M1 repolarization for CNV gene therapy","authors":"Yu Zhang MD ,&nbsp;Baorui Chu MD ,&nbsp;Qian Fan MD ,&nbsp;Xian Song MD ,&nbsp;Qian Xu MD ,&nbsp;Yi Qu MD","doi":"10.1016/j.nano.2024.102740","DOIUrl":"10.1016/j.nano.2024.102740","url":null,"abstract":"<div><p>Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis.</p><p>To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase β (IKKβ) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKβ siRNA-loaded liposome (siIKKβ-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKβ-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102740"},"PeriodicalIF":5.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065583","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}
引用次数: 0
Engineered photonic near-infrared light activated photothermal theranostic nanovaccine induced targeted remodeling of tumor microenvironment 工程光子近红外光激活光热疗法纳米疫苗诱导的肿瘤微环境靶向重塑。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-02-09 DOI: 10.1016/j.nano.2024.102738
Karunanidhi Gowsalya MSc , Babu Rithisa MSc , Yuvaraj Haldorai PhD , Krishnamurthy Shanthi PhD , Raju Vivek PhD

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.

肿瘤复发是肿瘤学中的一个主要问题,它是由于手术和化疗等治疗后肿瘤细胞和小病灶的持续存在而导致的。本文提出了一种利用由光子 HCuS 组成的治疗纳米疫苗来解决这一问题的策略。这种纳米疫苗旨在消灭癌细胞及其痕迹,同时通过优化光热免疫影响防止肿瘤复发。成功的膜靶向可将新的治疗药物引入肿瘤细胞。HCuS和ICG与共封装的Toll-Like Receptors (TLR7/8)激动剂R848一起用于激活T细胞和成熟的DC,其综合效应可作为光热剂,在近红外光的作用下产生热量。事实证明,光热介导的免疫疗法与治疗模式能成功杀死肿瘤细胞。通过激活免疫系统,这种新型光子纳米疫苗大大增加了免疫原性细胞死亡(ICD),杀死肿瘤细胞并防止其复发。
{"title":"Engineered photonic near-infrared light activated photothermal theranostic nanovaccine induced targeted remodeling of tumor microenvironment","authors":"Karunanidhi Gowsalya MSc ,&nbsp;Babu Rithisa MSc ,&nbsp;Yuvaraj Haldorai PhD ,&nbsp;Krishnamurthy Shanthi PhD ,&nbsp;Raju Vivek PhD","doi":"10.1016/j.nano.2024.102738","DOIUrl":"10.1016/j.nano.2024.102738","url":null,"abstract":"<div><p>Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102738"},"PeriodicalIF":5.4,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716266","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}
引用次数: 0
Multifunctional nanocoatings with synergistic controlled release of zinc ions and cytokines for precise modulation of vascular intimal reconstruction 协同控制锌离子和细胞因子释放的多功能纳米涂层,用于精确调节血管内膜重建。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-02-08 DOI: 10.1016/j.nano.2024.102739
Jianying Tan PhD , Huanran Wang Master's degree in engineering , Sainan Liu Master's degree in engineering , Li Li PhD , Hengquan Liu PhD , Tao Liu PhD , Junying Chen PhD

Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.

血管支架植入术仍是目前治疗心血管疾病的主要方法。我们在此将重要的生物功能因子(SDF-1α、VEGF)和重要的金属离子(Zn2+)引入支架表面,探索它们在微环境中的协同作用。众所周知,不同因子的组合能有效调节细胞炎症反应,并选择性地调节细胞生物学行为。同时,在实施的方法中,VEGF 和 Zn2+ 被载入肝素和聚赖氨酸(Hep-PLL)纳米颗粒中,确保了功能分子的可控释放,具有多因素协同效应和优异的体内外生物功能。值得注意的是,改良支架在兔子体内植入 150 天后,可获得薄而光滑的新内膜。这项研究为构建改良表面微环境和促进组织修复提供了新思路。
{"title":"Multifunctional nanocoatings with synergistic controlled release of zinc ions and cytokines for precise modulation of vascular intimal reconstruction","authors":"Jianying Tan PhD ,&nbsp;Huanran Wang Master's degree in engineering ,&nbsp;Sainan Liu Master's degree in engineering ,&nbsp;Li Li PhD ,&nbsp;Hengquan Liu PhD ,&nbsp;Tao Liu PhD ,&nbsp;Junying Chen PhD","doi":"10.1016/j.nano.2024.102739","DOIUrl":"10.1016/j.nano.2024.102739","url":null,"abstract":"<div><p>Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn<sup>2+</sup>) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn<sup>2+</sup> were loaded into heparin and poly-<span>l</span>-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions <em>in vitro</em> and <em>in vivo</em>. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102739"},"PeriodicalIF":5.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716268","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}
引用次数: 0
FT-Raman spectra in combination with machine learning and multivariate analyses as a diagnostic tool in brain tumors 傅立叶变换拉曼光谱与机器学习和多元分析相结合,作为脑肿瘤的诊断工具。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-02-08 DOI: 10.1016/j.nano.2024.102737
Bartłomiej Tołpa MSc , Wiesław Paja Dr , Elżbieta Trojnar MSc , Kornelia Łach MSc , Agnieszka Gala-Błądzińska Dr , Aneta Kowal MSc , Ewelina Gumbarewicz Dr , Paulina Frączek MSc , Józef Cebulski Dr , Joanna Depciuch Dr

Brain tumors are one of the most dangerous, because the position of these are in the organ that governs all life processes. Moreover, a lot of brain tumor types were observed, but only one main diagnostic method was used – histopathology, for which preparation of sample was long. Consequently, a new, quicker diagnostic method is needed. In this paper, FT-Raman spectra of brain tissues were analyzed by Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), four different machine learning (ML) algorithms to show possibility of differentiating between glioblastoma G4 and meningiomas, as well as two different types of meningiomas (atypical and angiomatous). Obtained results showed that in meningiomas additional peak around 1503 cm−1 and higher level of amides was noticed in comparison with glioblastoma G4. In the case of meningiomas differentiation, in angiomatous meningiomas tissues lower level of lipids and polysaccharides were visible than in atypical meningiomas. Moreover, PCA analyses showed higher distinction between glioblastoma G4 and meningiomas in the FT-Raman range between 800 cm−1 and 1800 cm−1 and between two types of meningiomas in the range between 2700 cm−1 and 3000 cm−1. Decision trees showed, that the most important peaks to differentiate glioblastoma and meningiomas were at 1151 cm−1 and 2836 cm−1 while for angiomatous and atypical meningiomas – 1514 cm−1 and 2875 cm−1. Furthermore, the accuracy of obtained results for glioblastoma G4 and meningiomas was 88 %, while for meningiomas – 92 %. Consequently, obtained data showed possibility of using FT-Raman spectroscopy in diagnosis of different types of brain tumors.

脑肿瘤是最危险的肿瘤之一,因为它们位于支配所有生命过程的器官中。此外,人们还观察到许多脑肿瘤类型,但只使用一种主要诊断方法--组织病理学,而准备样本的时间很长。因此,需要一种新的、更快捷的诊断方法。本文通过主成分分析(PCA)、层次聚类分析(HCA)和四种不同的机器学习(ML)算法对脑组织的傅立叶变换拉曼光谱进行了分析,以显示区分 G4 型胶质母细胞瘤和脑膜瘤以及两种不同类型脑膜瘤(非典型和血管瘤)的可能性。研究结果表明,与 G4 型胶质母细胞瘤相比,脑膜瘤在 1503 cm-1 附近出现了额外的峰值,酰胺含量更高。在脑膜瘤分化方面,血管瘤型脑膜瘤组织中的脂质和多糖含量低于非典型脑膜瘤。此外,PCA 分析表明,在 800 厘米-1 至 1800 厘米-1 的傅立叶变换拉曼光谱范围内,胶质母细胞瘤 G4 和脑膜瘤之间的区分度较高,而在 2700 厘米-1 至 3000 厘米-1 的范围内,两种类型的脑膜瘤之间的区分度较高。决策树显示,区分胶质母细胞瘤和脑膜瘤最重要的峰值是 1151 cm-1 和 2836 cm-1,而区分血管瘤和非典型脑膜瘤最重要的峰值是 1514 cm-1 和 2875 cm-1。此外,G4 型胶质母细胞瘤和脑膜瘤的准确率为 88%,脑膜瘤的准确率为 92%。因此,获得的数据表明傅立叶变换拉曼光谱可用于诊断不同类型的脑肿瘤。
{"title":"FT-Raman spectra in combination with machine learning and multivariate analyses as a diagnostic tool in brain tumors","authors":"Bartłomiej Tołpa MSc ,&nbsp;Wiesław Paja Dr ,&nbsp;Elżbieta Trojnar MSc ,&nbsp;Kornelia Łach MSc ,&nbsp;Agnieszka Gala-Błądzińska Dr ,&nbsp;Aneta Kowal MSc ,&nbsp;Ewelina Gumbarewicz Dr ,&nbsp;Paulina Frączek MSc ,&nbsp;Józef Cebulski Dr ,&nbsp;Joanna Depciuch Dr","doi":"10.1016/j.nano.2024.102737","DOIUrl":"10.1016/j.nano.2024.102737","url":null,"abstract":"<div><p>Brain tumors are one of the most dangerous, because the position of these are in the organ that governs all life processes. Moreover, a lot of brain tumor types were observed, but only one main diagnostic method was used – histopathology, for which preparation of sample was long. Consequently, a new, quicker diagnostic method is needed. In this paper, FT-Raman spectra of brain tissues were analyzed by Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), four different machine learning (ML) algorithms to show possibility of differentiating between glioblastoma G4 and meningiomas, as well as two different types of meningiomas (atypical and angiomatous). Obtained results showed that in meningiomas additional peak around 1503 cm<sup>−1</sup> and higher level of amides was noticed in comparison with glioblastoma G4. In the case of meningiomas differentiation, in angiomatous meningiomas tissues lower level of lipids and polysaccharides were visible than in atypical meningiomas. Moreover, PCA analyses showed higher distinction between glioblastoma G4 and meningiomas in the FT-Raman range between 800 cm<sup>−1</sup> and 1800 cm<sup>−1</sup> and between two types of meningiomas in the range between 2700 cm<sup>−1</sup> and 3000 cm<sup>−1</sup>. Decision trees showed, that the most important peaks to differentiate glioblastoma and meningiomas were at 1151 cm<sup>−1</sup> and 2836 cm<sup>−1</sup> while for angiomatous and atypical meningiomas – 1514 cm<sup>−1</sup> and 2875 cm<sup>−1</sup>. Furthermore, the accuracy of obtained results for glioblastoma G4 and meningiomas was 88 %, while for meningiomas – 92 %. Consequently, obtained data showed possibility of using FT-Raman spectroscopy in diagnosis of different types of brain tumors.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102737"},"PeriodicalIF":5.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716267","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}
引用次数: 0
Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis 在小鼠骨关节炎模型中,单剂量热冲击性地塞米松原药可在 15 周内完全缓解关节疼痛
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-01-29 DOI: 10.1016/j.nano.2024.102735
Ningrong Chen PhD , Xin Wei PhD , Gang Zhao PhD , Zhenshan Jia PhD , Xin Fu PhD , Haochen Jiang BS , Xiaoke Xu BSc , Zhifeng Zhao PhD , Purva Singh PhD , Samantha Lessard BA , Miguel Otero PhD , Mary B. Goldring PhD , Steven R. Goldring MD , Dong Wang PhD

In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.

本研究旨在评估热致伸缩性聚合物地塞米松(Dex)原药(ProGel-Dex)在骨关节炎(OA)小鼠模型中的镇痛效果。在建立模型 12 周后,OA 小鼠接受 ProGel-Dex、剂量相当的 Dex 或生理盐水的单次关节内注射。与生理盐水和地塞米松对照组相比,ProGel-Dex能在15周的无行为能力测试中提供完全和持续的疼痛缓解。体内光学成像证实,在注射后的15周内,ProGel-Dex一直存在于关节中。根据显微 CT 分析,ProGel-Dex 治疗小鼠的软骨下骨厚度和内侧半月板骨量明显低于 Dex 和生理盐水对照组。除了体重增加的短暂延迟和终点肝脏和脾脏重量略微降低外,ProGel-Dex 治疗后没有观察到其他不良反应。这些研究结果表明,ProGel-Dex 有可能成为一种有效、安全的镇痛剂,用于治疗 OA 疼痛。
{"title":"Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis","authors":"Ningrong Chen PhD ,&nbsp;Xin Wei PhD ,&nbsp;Gang Zhao PhD ,&nbsp;Zhenshan Jia PhD ,&nbsp;Xin Fu PhD ,&nbsp;Haochen Jiang BS ,&nbsp;Xiaoke Xu BSc ,&nbsp;Zhifeng Zhao PhD ,&nbsp;Purva Singh PhD ,&nbsp;Samantha Lessard BA ,&nbsp;Miguel Otero PhD ,&nbsp;Mary B. Goldring PhD ,&nbsp;Steven R. Goldring MD ,&nbsp;Dong Wang PhD","doi":"10.1016/j.nano.2024.102735","DOIUrl":"10.1016/j.nano.2024.102735","url":null,"abstract":"<div><p><span><span>In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric </span>dexamethasone (Dex) </span>prodrug<span><span> (ProGel-Dex) in a mouse model of osteoarthritis<span> (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for &gt;15 weeks according to incapacitance tests. In vivo optical imaging<span><span><span> confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower </span>subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and </span>spleen weights, no other adverse effect was observed after ProGel-Dex </span></span></span>treatment<span>. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102735"},"PeriodicalIF":5.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584432","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}
引用次数: 0
New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation 用于基于红外灯的皮肤癌光疗的新型石墨烯药物制剂:体外验证和体内人体皮肤渗透性
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-01-29 DOI: 10.1016/j.nano.2024.102734
Filipa A.L.S. Silva MSc , Soraia Pinto MSc , Susana G. Santos PhD , Fernão D. Magalhães PhD , Bruno Sarmento PhD , Artur M. Pinto PhD

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm−2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 μg mL−1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 μg mL−1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 μg mL−1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.

基底细胞癌(BCC)是人类癌症中最常见的一种,治疗方法通常包括手术,但也需要其他替代策略。我们建议使用carbopol水凝胶(HG)局部施用纳米氧化物(GOn)和部分还原纳米氧化物(p-rGOn),用于BCC的光热疗法(PTT)。进入 HG 的 GOn 和 p-rGOn 的横向尺寸约为 200 nm,可在 8 个月内保持稳定。用红外线(IR)光热疗法灯源(15.70 mW cm-2)照射 20 分钟后,GOn-HG 的温度升至 44.7 ℃,而 p-rGOn-HG 的温度则达到 47.0 ℃。用这两种水凝胶(250 μg mL-1)培养的人皮肤成纤维细胞(HFF-1)都能保持其形态和活力。经过 20 分钟红外照射后,p-rGOn HG(250 μg mL-1)可完全消灭皮肤癌细胞(A-431)。体内人体皮肤渗透性测试表明,GO HG 可在 2.0 小时内,p-rGOn HG 可在 0.5 小时内,在皮肤内成功达到治疗浓度(250 μg mL-1)。
{"title":"New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation","authors":"Filipa A.L.S. Silva MSc ,&nbsp;Soraia Pinto MSc ,&nbsp;Susana G. Santos PhD ,&nbsp;Fernão D. Magalhães PhD ,&nbsp;Bruno Sarmento PhD ,&nbsp;Artur M. Pinto PhD","doi":"10.1016/j.nano.2024.102734","DOIUrl":"10.1016/j.nano.2024.102734","url":null,"abstract":"<div><p>Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm<sup>−2</sup>), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 μg mL<sup>−1</sup>) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 μg mL<sup>−1</sup>) completely eradicated skin cancer cells (A-431). <em>Ex vivo</em> human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 μg mL<sup>−1</sup>) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"57 ","pages":"Article 102734"},"PeriodicalIF":5.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584415","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}
引用次数: 0
Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery 通过 mRNA 纳米输送恢复野生型 p53 抗癌的治疗潜力
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-01-08 DOI: 10.1016/j.nano.2024.102732
Divya Kamath PhD , Tomoo Iwakuma MD PhD , Stefan H. Bossmann PhD

Among the tumor suppressor genes, TP53 is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins. TP53 mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and progression (Yamamoto and Iwakuma, 2018; Zhang et al., 2022). TP53 has extensively been studied as a therapeutic target as well as for drug development and therapies, however with limited success. Achieving targeted therapies for restoration of WTp53 function and depletion or repair of mutant p53 (mutp53) will have far reaching implication in cancer treatment and therapies. This review briefly discusses the role of p53 mutation in cancer and the therapeutic potential of restoring WTp53 through the advances in mRNA nanomedicine.

在肿瘤抑制基因中,TP53是人类癌症中最常发生突变的基因,大多数突变都是错义突变,导致产生突变p53(mutp53)蛋白。TP53突变不仅会导致作为转录因子和肿瘤抑制因子的功能缺失(LOH),还会获得野生型p53(WTp53)依赖的致癌功能,从而增强癌症的转移和进展(Yamamoto and Iwakuma, 2018; Zhang et al.)人们已将 TP53 作为治疗靶点以及药物开发和疗法进行了广泛研究,但成效有限。实现恢复 WTp53 功能和消耗或修复突变 p53(mutp53)的靶向疗法将对癌症治疗和疗法产生深远影响。本综述简要讨论了 p53 突变在癌症中的作用,以及通过 mRNA 纳米药物的进步恢复 WTp53 的治疗潜力。
{"title":"Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery","authors":"Divya Kamath PhD ,&nbsp;Tomoo Iwakuma MD PhD ,&nbsp;Stefan H. Bossmann PhD","doi":"10.1016/j.nano.2024.102732","DOIUrl":"10.1016/j.nano.2024.102732","url":null,"abstract":"<div><p>Among the tumor suppressor genes, <em>TP53</em> is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins. <em>TP53</em> mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and progression (Yamamoto and Iwakuma, 2018; Zhang et al., 2022). <em>TP53</em> has extensively been studied as a therapeutic target as well as for drug development and therapies, however with limited success. Achieving targeted therapies for restoration of WTp53 function and depletion or repair of mutant p53 (mutp53) will have far reaching implication in cancer treatment and therapies. This review briefly discusses the role of p53 mutation in cancer and the therapeutic potential of restoring WTp53 through the advances in mRNA nanomedicine.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102732"},"PeriodicalIF":5.4,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000017/pdfft?md5=3bfb6c54e10c88db00aebb3109581026&pid=1-s2.0-S1549963424000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397746","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}
引用次数: 0
A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs 一种 PEG 化的丙氯苯嗪脂质体制剂,可限制脑部暴露,但仍能保持动态胺 II 的活性:接受化疗 mAbs 的癌症患者的潜在辅助疗法
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-01-08 DOI: 10.1016/j.nano.2024.102733
Christopher N. Subasic , Fiona Simpson , Rodney F. Minchin , Lisa M. Kaminskas

Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.

由于与抗体结合的细胞表面受体的快速内吞作用,抗癌单克隆抗体往往无法为受体阳性患者带来治疗效果。大剂量联合使用丙氯苯嗪(PCZ)可抑制内吞,并通过抑制动态胺 II 使肿瘤对 mAbs 敏感,但也会带来神经系统副作用。我们研究了使用 PCZ 的 PEG 化脂质体制剂(LPCZ)的可能性,以保留 PCZ 的抗癌效果,但限制脑部吸收。不带电的脂质体显示出完全的药物包囊和pH值依赖性药物释放,而阳离子脂质体则显示出有限的药物包囊和缺乏pH值依赖性药物释放。在KJD细胞中,不带电的LPCZ对表皮生长因子受体内化的抑制作用与游离PCZ相当。大鼠静脉注射 PCZ 后,与静脉注射 PCZ 相比,LPCZ 降低了 PCZ 的血浆清除率和脑摄取量。这些结果表明,LPCZ作为一种辅助疗法,可为接受mAb治疗的癌症患者带来比PCZ更多的益处。
{"title":"A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs","authors":"Christopher N. Subasic ,&nbsp;Fiona Simpson ,&nbsp;Rodney F. Minchin ,&nbsp;Lisa M. Kaminskas","doi":"10.1016/j.nano.2024.102733","DOIUrl":"10.1016/j.nano.2024.102733","url":null,"abstract":"<div><p>Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102733"},"PeriodicalIF":5.4,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000029/pdfft?md5=d9885184d3ca15297423f751a561d6e6&pid=1-s2.0-S1549963424000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397933","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}
引用次数: 0
Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation 通过基于 HPMA 共聚物的具有 pH 值敏感性的纳米疗法同时递送 STAT3 抑制剂和多柔比星,实现对肿瘤的化疗增敏
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-27 DOI: 10.1016/j.nano.2023.102730
M. Kovář PhD , V. Šubr PhD , K. Běhalová MSc , M. Studenovský PhD , D. Starenko MSc , J. Kovářová PhD , P. Procházková PhD , T. Etrych PhD, DSc , L. Kostka PhD

We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1–3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC50 ~0.6–7.9 μM and 0.7–10.9 μM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors.

我们合成了三种新型 STAT3 抑制剂(S3iD1-S3iD3),它们具有氧化庚酸残基,可通过 pH 敏感的腙键与 HPMA 共聚物载体连接。我们合成了含有多柔比星(Dox)和 STAT3 抑制剂的 HPMA 共聚物共轭物,以评估多柔比星和 STAT3 抑制剂联合递送到肿瘤中的抗癌效果。S3iD1-3 及其共聚物结合的对应物(P-S3iD1-P-S3iD3)在五种小鼠和人类癌细胞系中显示出相当高的体外细胞抑制活性,IC50 分别为 ~0.6-7.9 μM 和 0.7-10.9 μM。S3iD2 和 S3iD3 被证实能抑制 STAT3 信号通路。HPMA共聚物结合Dox(P-Dox)和P-S3iD3以可忽略不计的毒性剂量组合在B16F10黑色素瘤小鼠中显示出显著的抗肿瘤活性,15只小鼠中有2只完全治愈。而单用 P-Dox 的治疗活性明显较低,没有完全治愈的小鼠。因此,含有 STAT3 抑制剂的聚合物共轭物可用于化疗难治性肿瘤的化疗增敏。
{"title":"Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation","authors":"M. Kovář PhD ,&nbsp;V. Šubr PhD ,&nbsp;K. Běhalová MSc ,&nbsp;M. Studenovský PhD ,&nbsp;D. Starenko MSc ,&nbsp;J. Kovářová PhD ,&nbsp;P. Procházková PhD ,&nbsp;T. Etrych PhD, DSc ,&nbsp;L. Kostka PhD","doi":"10.1016/j.nano.2023.102730","DOIUrl":"10.1016/j.nano.2023.102730","url":null,"abstract":"<div><p>We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1–3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC<sub>50</sub> ~0.6–7.9 μM and 0.7–10.9 μM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102730"},"PeriodicalIF":5.4,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000813/pdfft?md5=0b22e39da0d9dbd9f7c2df39ae999db8&pid=1-s2.0-S1549963423000813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139069566","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}
引用次数: 0
期刊
Nanomedicine : nanotechnology, biology, and medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1