Pub Date : 2024-08-22DOI: 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.
{"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 , 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","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}
Pub Date : 2024-08-22DOI: 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.
{"title":"In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study","authors":"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.","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}
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, Kohei Sano PhD, Rin Kawakami BS, Shiho Tanaka BS, Masayuki Munekane PhD, Toshihide Yamasaki PhD, 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}
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.
{"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 , 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","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> < 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.</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}
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.
{"title":"Robust aptamer-targeted CRISPR/Cas9 delivery using mesenchymal stem cell membrane –liposome hybrid: BIRC5 gene knockout against melanoma","authors":"Asma Ghaemi PhD , Khalil Abnous PhD , Seyed Mohammad Taghdisi PhD , Masoumeh Vakili-Azghandi PhD , Mohammad Ramezani PhD , 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}
Pub Date : 2024-08-05DOI: 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.
{"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 , 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","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}
Pub Date : 2024-08-05DOI: 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, Min Guan MD, Huili Ma MD, Xiaomeng Dong MD, Junfen Feng MD, Tong Zhang MD, 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 (>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}
Pub Date : 2024-08-03DOI: 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.
{"title":"Prophylactic and therapeutic cancer vaccine with continuous localized immunomodulation","authors":"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","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}
Pub Date : 2024-07-17DOI: 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.
{"title":"Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial","authors":"Oskar Axelsson PhD, Nooshin Yousefpour BSc, Olof Björnberg PhD, Erik Ekengard PhD, 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}
Pub Date : 2024-07-02DOI: 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.
{"title":"Brain-targeting redox-sensitive micelles for codelivery of TMZ and β-lapachone for glioblastoma therapy","authors":"Yuxiang Dai MD , Yuanping Min MSc , Lu Zhou MM , Longyang Cheng MM , Hongbin Ni MD , Yang Yang PhD , 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}