首页 > 最新文献

Nanomedicine : nanotechnology, biology, and medicine最新文献

英文 中文
Identification of formulation parameters that affect the analgesic efficacy of ProGel-Dex – A thermoresponsive polymeric dexamethasone prodrug for chronic arthritis pain relief 确定影响 ProGel-Dex 镇痛效果的配方参数--一种用于缓解慢性关节炎疼痛的热致伸缩性聚合地塞米松原药。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-22 DOI: 10.1016/j.nano.2024.102782
Xin Wei PhD , Gang Zhao PhD , Ningrong Chen PhD , Xiaoke Xu BS , Haochen Jiang BS , Daniel Tran BS , Evan Glissmeyer BS , Mary B. Goldring PhD , Steven R. Goldring MD , Dong Wang PhD

The relief of joint pain is one of the main objectives in the clinical management of arthritis. Although significant strides have been made in improving management of rheumatoid and related forms of inflammatory arthritis, there are still major unmet needs for therapies that selectively provide potent, sustained and safe joint pain relief, especially among patients with osteoarthritis (OA), the most common form of arthritis. We have recently developed ProGel-Dex, an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug, which forms a hydrogel upon intra-articular administration and provides sustained improvement in pain-related behavior and inflammation in rodent models of arthritis. The focus of the present study was to investigate the impact of ProGel-Dex formulation parameters on its physicochemical properties and in vivo efficacy. The results of this study provide essential knowledge for the future design of ProGel-Dex that can provide more effective, sustained and safe relief of joint pain and inflammation.

缓解关节疼痛是关节炎临床治疗的主要目标之一。尽管在改善类风湿性关节炎和相关炎症性关节炎的治疗方面取得了重大进展,但对于选择性地提供强效、持续和安全的关节疼痛缓解的疗法,特别是对于最常见的骨关节炎(OA)患者来说,仍有大量需求未得到满足。我们最近开发了 ProGel-Dex,这是一种基于 N-(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物的热致伸缩性地塞米松(Dex)原药,在关节内给药后形成水凝胶,可持续改善啮齿类动物关节炎模型中与疼痛相关的行为和炎症。本研究的重点是调查 ProGel-Dex 配方参数对其理化性质和体内疗效的影响。本研究的结果为今后设计能更有效、持续、安全地缓解关节疼痛和炎症的 ProGel-Dex 提供了重要的知识。
{"title":"Identification of formulation parameters that affect the analgesic efficacy of ProGel-Dex – A thermoresponsive polymeric dexamethasone prodrug for chronic arthritis pain relief","authors":"Xin Wei PhD ,&nbsp;Gang Zhao PhD ,&nbsp;Ningrong Chen PhD ,&nbsp;Xiaoke Xu BS ,&nbsp;Haochen Jiang BS ,&nbsp;Daniel Tran BS ,&nbsp;Evan Glissmeyer BS ,&nbsp;Mary B. Goldring PhD ,&nbsp;Steven R. Goldring MD ,&nbsp;Dong Wang PhD","doi":"10.1016/j.nano.2024.102782","DOIUrl":"10.1016/j.nano.2024.102782","url":null,"abstract":"<div><p>The relief of joint pain is one of the main objectives in the clinical management of arthritis. Although significant strides have been made in improving management of rheumatoid and related forms of inflammatory arthritis, there are still major unmet needs for therapies that selectively provide potent, sustained and safe joint pain relief, especially among patients with osteoarthritis (OA), the most common form of arthritis. We have recently developed ProGel-Dex, an <em>N</em>-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug, which forms a hydrogel upon intra-articular administration and provides sustained improvement in pain-related behavior and inflammation in rodent models of arthritis. The focus of the present study was to investigate the impact of ProGel-Dex formulation parameters on its physicochemical properties and <em>in vivo</em> efficacy. The results of this study provide essential knowledge for the future design of ProGel-Dex that can provide more effective, sustained and safe relief of joint pain and inflammation.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102782"},"PeriodicalIF":4.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046928","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
In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study 体外评估纳米药物导致掌跖红斑痛的倾向:Doxil与多柔比星对比案例研究。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-22 DOI: 10.1016/j.nano.2024.102780
Edward Cedrone B.S. , Abbas Ishaq Ph.D. , Emma Grabarnik Ph.D. , Elijah Edmondson DVM., Ph.D. , Sarah Skoczen M.S. , Barry W. Neun B.S. , Matthew Freer Ph.D. , Siannah Shuttleworth M.Res. , Lisbet Sviland M.D., Ph.D. , Anne Dickinson Ph.D. , Marina A. Dobrovolskaia Ph.D.

Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models. Therefore, there is a need for reliable models that would allow the detection of this toxicity early during the drug development process. Herein, we describe the use of an in vitro skin explant assay to assess traditional DXR, Doxil reference listed drug (RLD) and two generic PEGylated liposomal DXR formulations for their abilities to cause inflammation and skin damage. We demonstrate that the results obtained with the in vitro skin explant assay model for traditional DXR and Doxil correlate with the clinical data.

掌跖红肿症(PPE)又称手足综合征,是一种以炎症介导的手掌和足底皮肤损伤为特征的疾病。PPE 限制了抗癌药物的成功治疗应用。然而,由于缺乏准确的体外和体内动物模型,在临床前研究中识别这种毒性具有挑战性。因此,有必要建立可靠的模型,以便在药物开发过程中及早发现这种毒性。在此,我们介绍了使用体外皮肤外植体检测法来评估传统的 DXR、多西尔参比上市药物(RLD)和两种通用的 PEG 化脂质体 DXR 制剂引起炎症和皮肤损伤的能力。我们证明,传统 DXR 和多西尔的体外皮肤外植体检测模型得出的结果与临床数据相关。
{"title":"In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study","authors":"Edward Cedrone B.S. ,&nbsp;Abbas Ishaq Ph.D. ,&nbsp;Emma Grabarnik Ph.D. ,&nbsp;Elijah Edmondson DVM., Ph.D. ,&nbsp;Sarah Skoczen M.S. ,&nbsp;Barry W. Neun B.S. ,&nbsp;Matthew Freer Ph.D. ,&nbsp;Siannah Shuttleworth M.Res. ,&nbsp;Lisbet Sviland M.D., Ph.D. ,&nbsp;Anne Dickinson Ph.D. ,&nbsp;Marina A. Dobrovolskaia Ph.D.","doi":"10.1016/j.nano.2024.102780","DOIUrl":"10.1016/j.nano.2024.102780","url":null,"abstract":"<div><p>Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models. Therefore, there is a need for reliable models that would allow the detection of this toxicity early during the drug development process. Herein, we describe the use of an in vitro skin explant assay to assess traditional DXR, Doxil reference listed drug (RLD) and two generic PEGylated liposomal DXR formulations for their abilities to cause inflammation and skin damage. We demonstrate that the results obtained with the in vitro skin explant assay model for traditional DXR and Doxil correlate with the clinical data.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102780"},"PeriodicalIF":4.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056128","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
Electrostatically self-assembled gold nanorods with sulfated hyaluronic acid for targeted photothermal therapy for CD44-positive tumors 含硫酸化透明质酸的静电自组装金纳米棒用于 CD44 阳性肿瘤的靶向光热疗法。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-18 DOI: 10.1016/j.nano.2024.102781
Toshie Tanaka PhD, Kohei Sano PhD, Rin Kawakami BS, Shiho Tanaka BS, Masayuki Munekane PhD, Toshihide Yamasaki PhD, Takahiro Mukai PhD

Gold nanorods (GNR) produce heat upon irradiation with near-infrared light, enabling a tumor-targeted photothermal therapy. In this study, we prepared GNR coated with sulfated hyaluronic acid (sHA) with a binding affinity for CD44 via electrostatic interactions to deliver GNR to tumors efficiently and stably, and evaluated their usefulness for photothermal therapy. Cationic GNR modified with trimethylammonium groups electrostatically interacted with native HA or sHA with varying degrees of sulfation to form complexes. While GNR/HA was unstable in saline, GNR/sHA maintained the absorbance peak in the near-infrared region, particularly for GNR/sHA with higher degrees of sulfation. GNR/sHA exhibited an intense photothermal effect upon irradiation with near-infrared light. Furthermore, in vitro and in vivo studies revealed that GNR coated with sHA containing approximately 1.2 sulfated groups per HA unit could accumulate in CD44-positive tumors via an HA-specific pathway. These findings indicate the effectiveness of GNR/sHA as a tumor-targeted photothermal therapeutic agent.

金纳米棒(GNRs)在近红外线照射下会产生热量,从而实现肿瘤靶向光热疗法。在这项研究中,我们制备了涂有硫酸化透明质酸(sHA)的 GNRs,通过静电相互作用与 CD44 产生结合亲和力,从而将 GNRs 高效、稳定地输送到肿瘤中,并评估了它们在光热疗法中的作用。用三甲基铵基团修饰的阳离子 GNR 与原生 HA 或不同硫酸化程度的 sHA 发生静电相互作用,形成复合物。GNR/HA 在生理盐水中不稳定,而 GNR/sHA 则在近红外区域保持吸光峰,特别是硫酸化程度较高的 GNR/sHA。在近红外线照射下,GNR/sHA 表现出强烈的光热效应。此外,体外和体内研究表明,涂有每 HA 单位含有约 1.2 个硫酸化基团的 sHA 的 GNR 可通过 HA 特异性途径在 CD44 阳性肿瘤中聚集。这些研究结果表明,GNR/SHA 是一种有效的肿瘤靶向光热治疗剂。
{"title":"Electrostatically self-assembled gold nanorods with sulfated hyaluronic acid for targeted photothermal therapy for CD44-positive tumors","authors":"Toshie Tanaka PhD,&nbsp;Kohei Sano PhD,&nbsp;Rin Kawakami BS,&nbsp;Shiho Tanaka BS,&nbsp;Masayuki Munekane PhD,&nbsp;Toshihide Yamasaki PhD,&nbsp;Takahiro Mukai PhD","doi":"10.1016/j.nano.2024.102781","DOIUrl":"10.1016/j.nano.2024.102781","url":null,"abstract":"<div><p>Gold nanorods (GNR) produce heat upon irradiation with near-infrared light, enabling a tumor-targeted photothermal therapy. In this study, we prepared GNR coated with sulfated hyaluronic acid (sHA) with a binding affinity for CD44 via electrostatic interactions to deliver GNR to tumors efficiently and stably, and evaluated their usefulness for photothermal therapy. Cationic GNR modified with trimethylammonium groups electrostatically interacted with native HA or sHA with varying degrees of sulfation to form complexes. While GNR/HA was unstable in saline, GNR/sHA maintained the absorbance peak in the near-infrared region, particularly for GNR/sHA with higher degrees of sulfation. GNR/sHA exhibited an intense photothermal effect upon irradiation with near-infrared light. Furthermore, in vitro and in vivo studies revealed that GNR coated with sHA containing approximately 1.2 sulfated groups per HA unit could accumulate in CD44-positive tumors via an HA-specific pathway. These findings indicate the effectiveness of GNR/sHA as a tumor-targeted photothermal therapeutic agent.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102781"},"PeriodicalIF":4.2,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009095","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
Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study 0.05 % 纳米包封咪喹莫特水凝胶治疗光化性咽颊炎的有效性和安全性:药物释放分析与临床研究。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-14 DOI: 10.1016/j.nano.2024.102779
Eduardo Liberato da Silva DDS, MSC , Erick Souza Pedraça DDS, MSc , Arthur Pias Salgueiro DDS, PhD , Rafaela Pletsch Gazzi MSc , Júlia Silveira Nunes DDS, MSc , Juliano Cavagni DDS, PhD , Marco Antônio Trevizani Martins DDS, PhD , Pantelis Varvaki Rados DDS, PhD , Adriana Raffin Pohlmann MSc, PhD , Silvia Stanisçuaski Guterres MSc, PhD , Luiza Abrahão Frank MSc, PhD , Fernanda Visioli DDS, PhD

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

光化性唇炎(AC)是一种唇部疾病,目前尚无标准治疗方法。咪喹莫特(IMIQ)是一种免疫调节剂,可治疗癌前病变;然而,其商业形式会导致严重的不良反应。本研究旨在评估含有 0.05 % 纳米胶囊化(NANO)咪喹莫特(IMIQ-0.05 %-NANO)的壳聚糖水凝胶中 IMQ 的释放情况及其在 AC 治疗中的疗效。水凝胶的制备方法是将壳聚糖加入装有 IMQ 的聚合物纳米胶囊(NCimiq)中,纳米胶囊是采用预成型聚合物界面沉积法生产的。使用自动弗朗兹细胞对 IMQ 的释放进行了评估。一项三盲随机对照试验(49 名受试者)比较了以下药物的疗效:IMIQ-0.05 %-NANO、5 % 游离咪喹莫特(IMIQ-5 %)、0.05 % 游离咪喹莫特(IMIQ-0.05 %)和安慰剂水凝胶。IMIQ-NANO-0.05 % 和 IMIQ-5 % 组的临床改善率明显更高(p
{"title":"Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study","authors":"Eduardo Liberato da Silva DDS, MSC ,&nbsp;Erick Souza Pedraça DDS, MSc ,&nbsp;Arthur Pias Salgueiro DDS, PhD ,&nbsp;Rafaela Pletsch Gazzi MSc ,&nbsp;Júlia Silveira Nunes DDS, MSc ,&nbsp;Juliano Cavagni DDS, PhD ,&nbsp;Marco Antônio Trevizani Martins DDS, PhD ,&nbsp;Pantelis Varvaki Rados DDS, PhD ,&nbsp;Adriana Raffin Pohlmann MSc, PhD ,&nbsp;Silvia Stanisçuaski Guterres MSc, PhD ,&nbsp;Luiza Abrahão Frank MSc, PhD ,&nbsp;Fernanda Visioli DDS, PhD","doi":"10.1016/j.nano.2024.102779","DOIUrl":"10.1016/j.nano.2024.102779","url":null,"abstract":"<div><p>Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (<em>p</em> &lt; 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p &lt; 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102779"},"PeriodicalIF":4.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988368","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
Robust aptamer-targeted CRISPR/Cas9 delivery using mesenchymal stem cell membrane –liposome hybrid: BIRC5 gene knockout against melanoma 利用间充质干细胞膜-脂质体杂交技术实现可靠的适配体靶向 CRISPR/Cas9 传输:针对黑色素瘤的 BIRC5 基因敲除。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-08 DOI: 10.1016/j.nano.2024.102778
Asma Ghaemi PhD , Khalil Abnous PhD , Seyed Mohammad Taghdisi PhD , Masoumeh Vakili-Azghandi PhD , Mohammad Ramezani PhD , Mona Alibolandi PhD

In this study, a platform was fabricated by combining a cationic lipid, 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) with mesenchymal stem cell membrane (MSCM) to produce a positively charged hybrid vesicle. The prepared hybrid vesicle was used to condense BIRC5 CRISPR/Cas9 plasmid for survivin (BIRC5) gene editing. The Sgc8-c aptamer (against protein tyrosine kinase 7) was then attached to the surface of the prepared NPs through electrostatic interactions. In this regard, melanoma cancer cells (B16F0 cell line) overexpressing PTK7 receptor could be targeted. Investigations were conducted on this system to evaluate its transfection efficiency, cellular toxicity, and therapeutic performance in preclinical stage using B16F0 tumor bearing C57BL/6 J mice. The results verified the superiority of the Hybrid/ BIRC5 compared to Liposome/ BIRC5 in terms of cellular toxicity and transfection efficiency. The cells exposure to Hybrid/BIRC5 significantly enhanced cytotoxicity. Moreover, cells treated with Apt-Hybrid/BIRC5 showed higher anti-proliferation activity toward PTK7-positive B16F0 cancer cells than that of the PKT7-negative CHO cell line. The active tumor targeting nanoparticles increased the cytotoxicity through down-regulation of BIRC5 expression as confirmed by Western blot analysis. In preclinical stage, Apt-Hybrid/BIRC5 showed remarkable tumor growth suppression toward B16F0 tumorized mice.

Thus, our study suggested that genome editing for BIRC5 through the CRISPR/Cas9 system could provide a potentially safe approach for melanoma cancer therapy and has great potential for clinical translation.

在这项研究中,通过将阳离子脂质--1,2-二油酰-3-三甲基铵丙烷(DOTAP)与间充质干细胞膜(MSCM)结合,制备出一种带正电荷的混合囊泡。制备好的混合囊泡用于凝集 BIRC5 CRISPR/Cas9 质粒,以进行存活素(BIRC5)基因编辑。然后通过静电相互作用将 Sgc8-c aptamer(针对蛋白酪氨酸激酶 7)连接到制备的 NPs 表面。这样,过度表达 PTK7 受体的黑色素瘤癌细胞(B16F0 细胞系)就可以成为靶标。研究人员利用携带 B16F0 肿瘤的 C57BL/6 J 小鼠对该系统进行了临床前研究,以评估其转染效率、细胞毒性和治疗效果。结果证实,就细胞毒性和转染效率而言,混合/BIRC5 比脂质体/BIRC5 更优越。细胞暴露于 Hybrid/BIRC5 后,细胞毒性明显增强。此外,与 PKT7 阴性的 CHO 细胞系相比,用 Apt-Hybrid/BIRC5 处理的细胞对 PTK7 阳性的 B16F0 癌细胞表现出更高的抗增殖活性。Western 印迹分析证实,活性肿瘤靶向纳米粒子通过下调 BIRC5 的表达增加了细胞毒性。在临床前阶段,Apt-Hybrid/BIRC5 对 B16F0 肿瘤小鼠的肿瘤生长有显著抑制作用。因此,我们的研究表明,通过CRISPR/Cas9系统对BIRC5进行基因组编辑可为黑色素瘤癌症治疗提供一种潜在的安全方法,并具有巨大的临床转化潜力。
{"title":"Robust aptamer-targeted CRISPR/Cas9 delivery using mesenchymal stem cell membrane –liposome hybrid: BIRC5 gene knockout against melanoma","authors":"Asma Ghaemi PhD ,&nbsp;Khalil Abnous PhD ,&nbsp;Seyed Mohammad Taghdisi PhD ,&nbsp;Masoumeh Vakili-Azghandi PhD ,&nbsp;Mohammad Ramezani PhD ,&nbsp;Mona Alibolandi PhD","doi":"10.1016/j.nano.2024.102778","DOIUrl":"10.1016/j.nano.2024.102778","url":null,"abstract":"<div><p>In this study, a platform was fabricated by combining a cationic lipid, 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) with mesenchymal stem cell membrane (MSCM) to produce a positively charged hybrid vesicle. The prepared hybrid vesicle was used to condense BIRC5 CRISPR/Cas9 plasmid for survivin (BIRC5) gene editing. The Sgc8-c aptamer (against protein tyrosine kinase 7) was then attached to the surface of the prepared NPs through electrostatic interactions. In this regard, melanoma cancer cells (B16F0 cell line) overexpressing PTK7 receptor could be targeted. Investigations were conducted on this system to evaluate its transfection efficiency, cellular toxicity, and therapeutic performance in preclinical stage using B16F0 tumor bearing C57BL/6 J mice. The results verified the superiority of the Hybrid/ BIRC5 compared to Liposome/ BIRC5 in terms of cellular toxicity and transfection efficiency. The cells exposure to Hybrid/BIRC5 significantly enhanced cytotoxicity. Moreover, cells treated with Apt-Hybrid/BIRC5 showed higher anti-proliferation activity toward PTK7-positive B16F0 cancer cells than that of the PKT7-negative CHO cell line. The active tumor targeting nanoparticles increased the cytotoxicity through down-regulation of BIRC5 expression as confirmed by Western blot analysis. In preclinical stage, Apt-Hybrid/BIRC5 showed remarkable tumor growth suppression toward B16F0 tumorized mice.</p><p>Thus, our study suggested that genome editing for BIRC5 through the CRISPR/Cas9 system could provide a potentially safe approach for melanoma cancer therapy and has great potential for clinical translation.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102778"},"PeriodicalIF":4.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913396","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
Exploring the anti-myeloma potential of composite nanoparticles As4S4/Fe3O4: Insights from in vitro, ex vivo and in vivo studies 探索 As4S4/Fe3O4 复合纳米粒子的抗骨髓瘤潜力:体外、体内和体外研究的启示。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-05 DOI: 10.1016/j.nano.2024.102777
Danka Cholujova PhD , Zdenka Lukacova Bujnakova PhD , Erika Dutkova PhD , Zuzana Valuskova , Nikoleta Csicsatkova PhD , Katarina Suroviakova , Maria Elisabeth Marinkovicova , Linda Zbellova , Lenka Koklesova , Jan Sedlak PhD , Teru Hideshima MD, PhD , Kenneth C. Anderson MD, PhD , Jana Jakubikova PhD

Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As4S4/Fe3O4 (4:1) and As4S4/Fe3O4 (1:1) demonstrated effective anti-MM activity in in vitro, ex vivo, and in vivo in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G2/M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As4S4/Fe3O4 (4:1) observed synergism with dexamethasone and melphalan, while As4S4/Fe3O4 (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM.

鉴于多发性骨髓瘤(MM)在恶性浆细胞(PCs)克隆增殖方面的深刻异质性和纳米疗法的抗MM治疗潜力,为MM患者制定治疗方案势在必行。As4S4/Fe3O4(4:1)和As4S4/Fe3O4(1:1)这两种复合纳米粒子(NPs)在体外、体内和异种移植小鼠模型中均显示出有效的抗MM活性。复合氧化萘引发了p-ERK1/2/p-JNK的激活,c-Myc、p-PI3K、p-4E-BP1的下调;G2/M细胞周期停滞,细胞周期蛋白B1、组蛋白H2AX/H3增加,p-ATR、p-Chk1/p-Chk2、p-H2AX/p-H3激活;以及树突酶和线粒体依赖性凋亡诱导。无论是单独使用还是在基质存在的情况下,NPs都能减少MM细胞中的干细胞样侧群。为了获得更高的临床反应率,As4S4/Fe3O4(4:1)与地塞米松和美法仑协同作用,而As4S4/Fe3O4(1:1)与硼替佐米、来那度胺和泊马度胺等抗MM药物联用则显示出协同效应,这为在MM中进一步临床评估复合纳米粒子提供了框架。
{"title":"Exploring the anti-myeloma potential of composite nanoparticles As4S4/Fe3O4: Insights from in vitro, ex vivo and in vivo studies","authors":"Danka Cholujova PhD ,&nbsp;Zdenka Lukacova Bujnakova PhD ,&nbsp;Erika Dutkova PhD ,&nbsp;Zuzana Valuskova ,&nbsp;Nikoleta Csicsatkova PhD ,&nbsp;Katarina Suroviakova ,&nbsp;Maria Elisabeth Marinkovicova ,&nbsp;Linda Zbellova ,&nbsp;Lenka Koklesova ,&nbsp;Jan Sedlak PhD ,&nbsp;Teru Hideshima MD, PhD ,&nbsp;Kenneth C. Anderson MD, PhD ,&nbsp;Jana Jakubikova PhD","doi":"10.1016/j.nano.2024.102777","DOIUrl":"10.1016/j.nano.2024.102777","url":null,"abstract":"<div><p>Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As<sub>4</sub>S<sub>4</sub>/Fe<sub>3</sub>O<sub>4</sub> (4:1) and As<sub>4</sub>S<sub>4</sub>/Fe<sub>3</sub>O<sub>4</sub> (1:1) demonstrated effective anti-MM activity in <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G<sub>2</sub>/M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As<sub>4</sub>S<sub>4</sub>/Fe<sub>3</sub>O<sub>4</sub> (4:1) observed synergism with dexamethasone and melphalan, while As<sub>4</sub>S<sub>4</sub>/Fe<sub>3</sub>O<sub>4</sub> (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102777"},"PeriodicalIF":4.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000467/pdfft?md5=b83c7b1c404c8c4762085cf98d2dfb2d&pid=1-s2.0-S1549963424000467-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902429","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
Gallic acid-selenium nanoparticles with dual anti-inflammatory and antioxidant functions for synergistic treatment of acute kidney injury 具有抗炎和抗氧化双重功能的没食子酸-硒纳米颗粒可协同治疗急性肾损伤。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-05 DOI: 10.1016/j.nano.2024.102775
Jie Zhou PhD, Min Guan MD, Huili Ma MD, Xiaomeng Dong MD, Junfen Feng MD, Tong Zhang MD, Yuxin Wei MD

The overexpression of inflammatory factors is closely related to the pathogenesis of acute kidney injury (AKI). Additionally, the overproduction of reactive oxygen species (ROS) further exacerbates the inflammatory response. In light of this, monotherapies focused solely on inflammation have proven to be suboptimal. Therefore, this study successfully developed a nanoparticle (SC@Se/GA) that possesses anti-inflammatory and antioxidant properties. The SC@Se/GA has a smaller size, better stability, and kidney-targeting. In vivo experiments showed that the GPx enzyme activity of SC@Se/GA increases by almost 50 % more than SC@Se alone, indicating its efficient ability to scavenge ROS. In the meantime, SC@Se/GA has a longer renal retention period (>24 h) than free drug GA, which can dramatically lower the levels of inflammatory factors TNF-α and IL-6. In summary, SC@Se/GA, through its synergistic anti-inflammatory and antioxidant effects, markedly alleviates CDDP-induced renal injury and restores renal function, providing a new effective strategy for treating AKI.

炎症因子的过度表达与急性肾损伤(AKI)的发病机制密切相关。此外,活性氧(ROS)的过度产生进一步加剧了炎症反应。有鉴于此,仅针对炎症的单一疗法已被证明是不理想的。因此,本研究成功开发了一种具有抗炎和抗氧化特性的纳米粒子(SC@Se/GA)。SC@Se/GA具有更小的尺寸、更好的稳定性和肾脏靶向性。体内实验表明,SC@Se/GA的GPx酶活性比单独的SC@Se提高了近50%,表明其具有高效清除ROS的能力。同时,与游离药物 GA 相比,SC@Se/GA 在肾脏的滞留时间更长(>24 h),可显著降低炎症因子 TNF-α 和 IL-6 的水平。总之,SC@Se/GA通过其协同抗炎和抗氧化作用,可明显缓解CDDP诱导的肾损伤并恢复肾功能,为治疗AKI提供了一种新的有效策略。
{"title":"Gallic acid-selenium nanoparticles with dual anti-inflammatory and antioxidant functions for synergistic treatment of acute kidney injury","authors":"Jie Zhou PhD,&nbsp;Min Guan MD,&nbsp;Huili Ma MD,&nbsp;Xiaomeng Dong MD,&nbsp;Junfen Feng MD,&nbsp;Tong Zhang MD,&nbsp;Yuxin Wei MD","doi":"10.1016/j.nano.2024.102775","DOIUrl":"10.1016/j.nano.2024.102775","url":null,"abstract":"<div><p>The overexpression of inflammatory factors is closely related to the pathogenesis of acute kidney injury (AKI). Additionally, the overproduction of reactive oxygen species (ROS) further exacerbates the inflammatory response. In light of this, monotherapies focused solely on inflammation have proven to be suboptimal. Therefore, this study successfully developed a nanoparticle (SC@Se/GA) that possesses anti-inflammatory and antioxidant properties. The SC@Se/GA has a smaller size, better stability, and kidney-targeting. In vivo experiments showed that the GPx enzyme activity of SC@Se/GA increases by almost 50 % more than SC@Se alone, indicating its efficient ability to scavenge ROS. In the meantime, SC@Se/GA has a longer renal retention period (&gt;24 h) than free drug GA, which can dramatically lower the levels of inflammatory factors TNF-α and IL-6. In summary, SC@Se/GA, through its synergistic anti-inflammatory and antioxidant effects, markedly alleviates CDDP-induced renal injury and restores renal function, providing a new effective strategy for treating AKI.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102775"},"PeriodicalIF":4.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902441","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
Prophylactic and therapeutic cancer vaccine with continuous localized immunomodulation 具有持续局部免疫调节作用的预防性和治疗性癌症疫苗。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-03 DOI: 10.1016/j.nano.2024.102776
Nikitha Kota B.S. , Daniel Davila Gonzalez MD, PhD , Hsuan-Chen Liu PhD , Dixita Viswanath MD, PhD , Robin Vander Pol BS , Anthony Wood BS , Nicola Di Trani PhD , Corrine Ying Xuan Chua PhD , Alessandro Grattoni PhD

Selective in vivo immune cell manipulation offers a promising strategy for cancer vaccines. In this context, spatiotemporal control over recruitment of specific cells, and their direct exposure to appropriate immunoadjuvants and antigens are key to effective cancer vaccines. We present an implantable 3D-printed cancer vaccine platform called the ‘NanoLymph’ that enables spatiotemporally-controlled recruitment and manipulation of immune cells in a subcutaneous site. Leveraging two reservoirs each for continuous immunoadjuvant release or antigen presentation, the NanoLymph attracts dendritic cells (DCs) on site and exposes them to tumor-associated antigens. Upon local antigen-specific activation, DCs are mobilized to initiate a systemic immune response. NanoLymph releasing granulocyte-macrophage colony-stimulating factor and CpG-oligodeoxynucleotides with irradiated whole cell tumor lysate inhibited tumor growth of B16F10 murine melanoma in a prophylactic and therapeutic vaccine setting. Overall, this study presents the NanoLymph as a versatile cancer vaccine development platform with replenishable and controlled local release of antigens and immunoadjuvants.

选择性体内免疫细胞操作为癌症疫苗提供了一种前景广阔的策略。在这种情况下,对特定细胞招募的时空控制以及它们与适当免疫佐剂和抗原的直接接触是有效癌症疫苗的关键。我们展示了一种名为 "NanoLymph "的植入式三维打印癌症疫苗平台,它能在皮下部位实现时空控制的免疫细胞招募和操纵。NanoLymph 利用两个可持续释放免疫佐剂或呈递抗原的储库,吸引树突状细胞(DC),使其接触肿瘤相关抗原。局部抗原特异性激活后,树突状细胞被动员起来,启动全身免疫反应。释放粒细胞-巨噬细胞集落刺激因子和CpG-寡脱氧核苷酸的纳米淋巴与辐照全细胞肿瘤裂解物一起,在预防和治疗疫苗环境中抑制了B16F10小鼠黑色素瘤的肿瘤生长。总之,这项研究表明,NanoLymph 是一种多功能癌症疫苗开发平台,可在局部补充和控制抗原和免疫佐剂的释放。
{"title":"Prophylactic and therapeutic cancer vaccine with continuous localized immunomodulation","authors":"Nikitha Kota B.S. ,&nbsp;Daniel Davila Gonzalez MD, PhD ,&nbsp;Hsuan-Chen Liu PhD ,&nbsp;Dixita Viswanath MD, PhD ,&nbsp;Robin Vander Pol BS ,&nbsp;Anthony Wood BS ,&nbsp;Nicola Di Trani PhD ,&nbsp;Corrine Ying Xuan Chua PhD ,&nbsp;Alessandro Grattoni PhD","doi":"10.1016/j.nano.2024.102776","DOIUrl":"10.1016/j.nano.2024.102776","url":null,"abstract":"<div><p>Selective in vivo immune cell manipulation offers a promising strategy for cancer vaccines. In this context, spatiotemporal control over recruitment of specific cells, and their direct exposure to appropriate immunoadjuvants and antigens are key to effective cancer vaccines. We present an implantable 3D-printed cancer vaccine platform called the ‘NanoLymph’ that enables spatiotemporally-controlled recruitment and manipulation of immune cells in a subcutaneous site. Leveraging two reservoirs each for continuous immunoadjuvant release or antigen presentation, the NanoLymph attracts dendritic cells (DCs) on site and exposes them to tumor-associated antigens. Upon local antigen-specific activation, DCs are mobilized to initiate a systemic immune response. NanoLymph releasing granulocyte-macrophage colony-stimulating factor and CpG-oligodeoxynucleotides with irradiated whole cell tumor lysate inhibited tumor growth of B16F10 murine melanoma in a prophylactic and therapeutic vaccine setting. Overall, this study presents the NanoLymph as a versatile cancer vaccine development platform with replenishable and controlled local release of antigens and immunoadjuvants.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102776"},"PeriodicalIF":4.2,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000455/pdfft?md5=a2b72962ebd4da121e46efb0f291f0dc&pid=1-s2.0-S1549963424000455-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893874","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
Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial 尺寸依赖性肾过滤模型解释了功能纳米粒子的人体药代动力学:SPAGOPIX-01 临床试验。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-17 DOI: 10.1016/j.nano.2024.102774
Oskar Axelsson PhD, Nooshin Yousefpour BSc, Olof Björnberg PhD, Erik Ekengard PhD, Sujinna Lekmeechai PhD

The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R2 = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.

病人服用基于纳米粒子的核磁共振成像造影剂 SN132D 后的药代动力学可以用与尺寸相关的清除机制来解释,并对这种行为进行了数值模拟。通过 ICP-OES 分析了 14 名患者血液样本中的硅(纳米粒子的一种成分)。药代动力学模型只有一个自由参数,依赖于造影剂的测量尺寸分布以及肾脏和心血管系统的既定特性。该模型与输注开始后十分钟到两周内的样本实验数据拟合良好(R2 = 0.9910)。这些结果支持人体肾脏过滤的截止直径为 5.5 纳米。实验与模型之间的一致性意味着血浆蛋白与纳米颗粒的结合很少或根本没有。
{"title":"Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial","authors":"Oskar Axelsson PhD,&nbsp;Nooshin Yousefpour BSc,&nbsp;Olof Björnberg PhD,&nbsp;Erik Ekengard PhD,&nbsp;Sujinna Lekmeechai PhD","doi":"10.1016/j.nano.2024.102774","DOIUrl":"10.1016/j.nano.2024.102774","url":null,"abstract":"<div><p>The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R<sup>2</sup> = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102774"},"PeriodicalIF":4.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000431/pdfft?md5=8601ad682c68920fc5432c9e86ab6def&pid=1-s2.0-S1549963424000431-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727551","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
Brain-targeting redox-sensitive micelles for codelivery of TMZ and β-lapachone for glioblastoma therapy 用于治疗胶质母细胞瘤的 TMZ 和 β-拉帕醌联合给药的脑靶向氧化还原敏感胶束。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-02 DOI: 10.1016/j.nano.2024.102772
Yuxiang Dai MD , Yuanping Min MSc , Lu Zhou MM , Longyang Cheng MM , Hongbin Ni MD , Yang Yang PhD , Wendi Zhou MSc

Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and β-lapachone (β-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.

胶质母细胞瘤(GBM)是一种发病率高、生存率低的中枢神经系统癌症。提高药物在血脑屏障(BBB)的穿透力和靶向疗效对改善治疗效果至关重要。在这项研究中,我们为替莫唑胺(TMZ)和β-拉帕醌(β-Lapa)开发了一种氧化还原敏感的靶向纳米给药系统(HCA-A2)。该系统以透明质酸(HA)为亲水基团,花生四烯酸(CA)为疏水基团,血管表皮生长因子-2(A2)为靶向基团。对照系统包括非氧化还原敏感型(HDA-A2)和非靶向型(HCA)。在体外,HCA-TMZ-Lapa胶束在模拟肿瘤微环境中24小时内释放了100%的有效载荷,而在正常条件下释放率为43.97%。与对照组相比,通过凝集素介导的内吞作用内化的 HCA-A2 胶束表现出更强的细胞毒性、更好的 BBB 穿透性和细胞摄取性。体内研究表明,HCA-A2 胶束对肿瘤生长的抑制作用更强,这表明它们具有治疗脑胶质瘤的潜力。
{"title":"Brain-targeting redox-sensitive micelles for codelivery of TMZ and β-lapachone for glioblastoma therapy","authors":"Yuxiang Dai MD ,&nbsp;Yuanping Min MSc ,&nbsp;Lu Zhou MM ,&nbsp;Longyang Cheng MM ,&nbsp;Hongbin Ni MD ,&nbsp;Yang Yang PhD ,&nbsp;Wendi Zhou MSc","doi":"10.1016/j.nano.2024.102772","DOIUrl":"10.1016/j.nano.2024.102772","url":null,"abstract":"<div><p>Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and β-lapachone (β-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"61 ","pages":"Article 102772"},"PeriodicalIF":4.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498531","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
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