Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry
{"title":"Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes","authors":"Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry","doi":"10.1002/adtp.202400281","DOIUrl":"https://doi.org/10.1002/adtp.202400281","url":null,"abstract":"<p>Iron oxide nanoparticles have been proposed for magnetic hyperthermia treatment of tumors. However, efficacy depends on the injection of large amounts of such nanoparticles and the equipment is costly. Here, a new thermal cancer treatment is described, in which a tumor containing a low concentration of nonpyrogenic pure iron oxide nanominerals coated with carboxy-methyl-dextran (M-CMD), corresponding to modified magnetosomes, are exposed to ultrasound. Heating PC3 prostate carcinoma cells between 43 and 46°C using ultrasound in the presence of M-CMD resulted in significant necrotic cell death. Furthermore, deposition of M-CMD containing 3 µg of iron per mm<sup>3</sup> of tumor in subcutaneous xenografts of PC3-Luc tumors of 150 mm<sup>3</sup> followed by 6 to 10 sessions of ultrasound application (1 W cm<sup>−2</sup>, 1 MHz) of 10 min each led to a tumor temperature of 43–46°C per session and to total tumor disappearance without regrowth over 6 months following treatment start. Sequential histological analyses of the tumor tissues revealed partial tumor occupation by M-CMD and an increase in cell death over time. Neither lesions, nor magnetosome accumulation were found in microscopic sections of various internal organs collected from treated mice euthanized 6 months after the beginning of the treatment, indicating that M-CMD may not lead to long-term side effects.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Celia Martín-Morales, Sofia Caspani, Manuel Desco, Célia Tavares de Sousa, María Victoria Gómez-Gaviro
{"title":"Controlled Drug Release Systems for Cerebrovascular Diseases (Adv. Therap. 1/2025)","authors":"Celia Martín-Morales, Sofia Caspani, Manuel Desco, Célia Tavares de Sousa, María Victoria Gómez-Gaviro","doi":"10.1002/adtp.202570001","DOIUrl":"https://doi.org/10.1002/adtp.202570001","url":null,"abstract":"<p>Different nanosystems orbiting around the Brain representing future therapies for cerebrovascular and neurodegenerative diseases. Some of these nanosystems are represented in the image: mesoporous silica nanoparticles, liposomes and gold nanoparticles, all of them with encapsulated drugs, to be able to release them in specific regions and treat some brain diseases. More details can be found in article 2400239 by Manuel Desco, María Victoria Gómez-Gaviro, and co-workers. Illustration designed by Celia Martín-Morales.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202570001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela C. Carvalho, Maria Nolasco Viseu Domingues, Gabriel Davi Marena, Ermei Mäkilä, Jiachen Li, Gésinda Geertsema-Doornbusch, Cleverton Roberto de Andrade, Marc C. A. Stuart, Mohammad-Ali Shahbazi, Ione Corrêa, Brandon W. Peterson, Jarno Salonen, Helena F. Florindo, Taís Maria Bauab, Marlus Chorilli, Hélder A. Santos
{"title":"Hybrid Nanoparticles Dual-Loaded With Curcumin and Benzydamine Hydrochloride for the Treatment of Vulvovaginal Candidiasis: From Development to Biological Application In Vitro and In Vivo (Adv. Therap. 1/2025)","authors":"Gabriela C. Carvalho, Maria Nolasco Viseu Domingues, Gabriel Davi Marena, Ermei Mäkilä, Jiachen Li, Gésinda Geertsema-Doornbusch, Cleverton Roberto de Andrade, Marc C. A. Stuart, Mohammad-Ali Shahbazi, Ione Corrêa, Brandon W. Peterson, Jarno Salonen, Helena F. Florindo, Taís Maria Bauab, Marlus Chorilli, Hélder A. Santos","doi":"10.1002/adtp.202570003","DOIUrl":"https://doi.org/10.1002/adtp.202570003","url":null,"abstract":"<p>This image represents a hybrid nanoparticle, dispersed in a thermos-responsive hydrogel, composed of mesoporous silica nanoparticles and liposome-like structure dual-loaded with curcumin and benzydamine hydrochloride for the treatment of vulvovaginal candidiasis. More details can be found in the article by Marlus Chorilli, Hélder A. Santos, and co-workers.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202570003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Effect of a Near-Infrared Responsive MTX-Mn3O4@PDA Nano-Delivery System on Rheumatoid Arthritis","authors":"Xinwei Zhang, Ziping Wang, Yu Bai, Yulun Hu, Qing Chen, Yueping Liu, Mingming Chang","doi":"10.1002/adtp.202400345","DOIUrl":"https://doi.org/10.1002/adtp.202400345","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory processes. RA, which is typically associated with the accumulation of hyperactive immune cells (HICs), particularly M1 proinflammatory macrophages, is accompanied by elevated levels of reactive oxygen species (ROS) and decreased pH in the synovial membranes of the joints. In this work, a nano-delivery system (MTX-Mn<sub>3</sub>O<sub>4</sub>@PDA) is designed that can deliver photothermal materials, ROS scavengers, and synovial fibroblast inhibitors at the joint site for the treatment of RA. After injecting MTX-Mn<sub>3</sub>O<sub>4</sub>@PDA into the inflamed site of RA, photothermal therapy is initiated by near-infrared (NIR) laser irradiation, which resulted in the death of activated inflammatory cells at the lesion site. While polydopamine (PDA) slowly dissociates under stimulation by a low pH microenvironment. Subsequently, excess ROS interacts with the Mn<sub>3</sub>O<sub>4</sub> nanozyme and the undissociated PDA nanozyme, promoting ROS clearance, while Methotrexate (MTX) inhibits the proliferation of synovial fibroblasts. Intra-articular injection of MTX-Mn<sub>3</sub>O<sub>4</sub>@PDA (7 mg kg<sup>−1</sup>) into collagen-induced arthritis mice demonstrated efficacy in reducing toe swelling and significantly alleviating synovial inflammation, bone erosion, and cartilage degeneration. This nano-delivery system has potential clinical applications for treating RA.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Advances in Promoting Bone Regeneration in Type 2 Diabetes Using Drug Delivery Vehicles and Vehicle-Free Therapeutics","authors":"Yasamin Pesaran Afsharian, Mostafa Rahimnejad, Sayed Mahmood Rabiee, Farideh Feizi, Hermann Seitz","doi":"10.1002/adtp.202400400","DOIUrl":"https://doi.org/10.1002/adtp.202400400","url":null,"abstract":"<p>The incidence of type 2 diabetes (T2DM) increases significantly worldwide. Due to consistent hyperglycemia, insulin resistance, and chronic inflammation, T2DM patients encounter osteoporosis and induced osteoporotic fracture risks. Antidiabetic drugs have been traditional therapies that seek to control blood glucose, balance bone metabolism, and favor systemic immunosuppression. However, such drugs impact bone quality and its nano-scale features in the long-term. Today, biomedical experts are continuously advancing drug delivery tools for local delivery of osteo-immunomodulatory agents in T2DM. It is demonstrated that bioavailability and release profile determine osteo-immunomodulatory and osteoconductivity outcomes of such therapeutics. This review focuses on introducing currently used local drug delivery vehicles in T2DM. The fabrication techniques of such biomaterial-based systems are thoroughly examined. Furthermore, the feasibility and the potential factors contributing to consistent release of bioactive agents are surveyed. Furthermore, the extent of in vivo responses is described in the context of current research examples. Targeted signaling mechanisms are also assessed in detail to elucidate the activated healing routes.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dohyeon Kim, Hyeongseop Keum, Ryeowon Kim, Jieun Choi, Monica Celine Prayogo, Hyunjin Kim, Duckhyang Shin, Sharif MD Abuzar, Seunghyun Jo, Pilhan Kim, Chang Ook Park, Sangyong Jon
{"title":"Synthetic Bilirubin-Based Nanomedicine Alleviates Atopic Dermatitis by Reducing Oxidative Stress and Modulating Immune Responses","authors":"Dohyeon Kim, Hyeongseop Keum, Ryeowon Kim, Jieun Choi, Monica Celine Prayogo, Hyunjin Kim, Duckhyang Shin, Sharif MD Abuzar, Seunghyun Jo, Pilhan Kim, Chang Ook Park, Sangyong Jon","doi":"10.1002/adtp.202400403","DOIUrl":"https://doi.org/10.1002/adtp.202400403","url":null,"abstract":"<p>Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a growing prevalence worldwide. Topical corticosteroids and non-steroidal calcineurin inhibitors (CNIs) are used as first-line therapies for AD, but various side effects limit their long-term use. Here, the first synthetic bilirubin(IIIα)-derived nanoparticle is reported, designated BRNP(IIIα), and shows that it exhibits robust antioxidative and immunomodulatory effects and effectively reduces the clinical symptoms of AD upon topical treatment. BRNP(IIIα) in 1% high molecular weight hyaluronic acid (BRNP(IIIα)/HA) readily infiltrates into the dermis layer, notably downregulates disease-associated reactive oxygen species (ROS) and inflammatory chemokines and cytokines, and suppresses the recruitment of leukocytes and mast cells to AD-induced lesions. BRNP(IIIα)/HA also significantly reduces the tissue-resident memory T cell population, suggesting that it may inhibit recurrence. Furthermore, BRNP(IIIα)/HA does not induce any adverse effect related to skin irritation/sensitization or eye irritation in human tissue. Collectively, the findings suggest that BRNP(IIIα)/HA may be useful as an alternative to corticosteroids or CNIs for the safe, effective, and long-term topical treatment of AD.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nimeet Desai, Deepak Sahel, Bhakti Kubal, Humzah Postwala, Yesha Shah, Vivek P Chavda, Clara Fernandes, Dharmendra K. Khatri, Lalitkumar K. Vora
{"title":"Role of the Extracellular Matrix in Cancer: Insights into Tumor Progression and Therapy","authors":"Nimeet Desai, Deepak Sahel, Bhakti Kubal, Humzah Postwala, Yesha Shah, Vivek P Chavda, Clara Fernandes, Dharmendra K. Khatri, Lalitkumar K. Vora","doi":"10.1002/adtp.202400370","DOIUrl":"https://doi.org/10.1002/adtp.202400370","url":null,"abstract":"<p>The extracellular matrix (ECM) serves not only as a structural scaffold but also as an active regulator of cancer progression, profoundly influencing tumor behaviour and the tumor microenvironment (TME). This review focuses into the pivotal role of ECM alterations in facilitating tumor metastasis and explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis and disrupt associated signalling pathways critical for tumor architecture and cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods to suppress its synthesis and enzymatic strategies to degrade it, thereby mitigating its tumor-promoting effects. The discussion extends to innovative approaches for modulating ECM stiffness, focusing on the roles of cancer-associated fibroblasts and lysyl oxidases, which are key contributors to ECM remodelling and mechanical signalling. By strategically modifying these ECM components, these interventions aim to enhance the efficacy of existing cancer treatments, tackle resistance mechanisms, and achieve more durable therapeutic outcomes. Insights from recent studies and clinical trials highlight the promise of these strategies in overcoming treatment resistance and improving patient outcomes. Advancing our understanding of ECM biology leads to the development of innovative and more effective cancer therapies.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paola Modicano, Marie-Luise Trutschel, Thüong Phan-Xuan, Bruno F. E. Matarèse, Laura Urbano, Mark Green, Karsten Mäder, Lea Ann Dailey
{"title":"Does Encapsulation of π-Conjugated Polymer Nanoparticles within Biodegradable PEG–PLGA Matrices Mitigate Photoinduced Free Radical Production and Phototoxicity?","authors":"Paola Modicano, Marie-Luise Trutschel, Thüong Phan-Xuan, Bruno F. E. Matarèse, Laura Urbano, Mark Green, Karsten Mäder, Lea Ann Dailey","doi":"10.1002/adtp.202400190","DOIUrl":"https://doi.org/10.1002/adtp.202400190","url":null,"abstract":"<p>Lipophilic π-conjugated polymers (CPs) encapsulated within self-assembling diblock copolymer poly(ethylene glycol) methyl ether-<i>block</i>-poly(lactide-<i>co</i>-glycolide) (PEG–PLGA) nanoparticles, are interesting candidates for photodynamic and photothermal therapies. Upon irradiation, CPs generate reactive oxygen species (ROS), which may either cause local phototoxicity or could be exploited for photodynamic therapy. The propensity of the PEG–PLGA matrix to scavenge ROS has never been investigated. Here the ability of two PEG–PLGA structures (PEG<sub>2 kDa</sub>–PLGA<sub>4.5 kDa</sub> vs PEG<sub>5 kDa</sub>–PLGA<sub>55 kDa</sub>) to mitigate the release of ROS generated by four different CPs (PFO, F8BT, CN-PPV, and PCPDTBT) following irradiation (5 J cm<sup>−2</sup>) at 385, 455, and 656 nm is studied. The molar content of the PEG–PLGA matrix, rather than the molecular weight or composition, appeared to be the most influential factor, i.e., lower molar concentrations of the matrix polymer are associated with significant increases in phototoxicity. Multivariate analysis reveals that the combination of CP photophysical properties and nanoparticle matrix properties are important for understanding CP nanoparticle-induced phototoxicity.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mofei Huang, Jing Pan, Shizuko Sei, Yian Wang, Ming You
{"title":"Targeting ACAT1 for Precision Chemo-Immunoprevention in Lung Cancer","authors":"Mofei Huang, Jing Pan, Shizuko Sei, Yian Wang, Ming You","doi":"10.1002/adtp.202400430","DOIUrl":"https://doi.org/10.1002/adtp.202400430","url":null,"abstract":"<p>Lung cancer (LC) is a leading cause of cancer-related deathworldwide, and altered cholesterol metabolism is a hallmark of cancer cells. Acyl-CoA:cholesterol acyltransferase 1(ACAT1), or Sterol O-acyltransferase 1 (SOAT1), isa key cholesterol esterification enzyme. Its overexpression promotes tumorprogression by accumulating cholesterol esters. Inhibition of ACAT1 also potentiatesCD8+ T cells medicated anti-tumor immunity by increasing plasma membranecholesterol level. This study, as the first of its kind, shows the ACAT1/SOAT1 overexpressioncorrelates with poor prognosis in early-stage lung adenocarcinoma (LUAD) patients.Long-term treatment with ACAT1 inhibitor avasimibe suppresses tumorigenesis inboth Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growthfactor receptor (EGFR) mutation-induced LC mouse models without overttoxicity. ACAT1 inhibition reduces tumor cell proliferation, migration, andinvasion and causes G0/G1 cell cycle arrest, while boosting CD8+ T cells'effector function and memory phenotype. Single-cell RNA sequencing reveals thatACAT1 inhibition downregulates cholesterol biosynthesis and central carbon andnitrogen metabolism pathways in tumor cells, while upregulating genes relatedto oxidative phosphorylation and fatty acid oxidation in CD8+ T cells. Finally, avasimibe improves the efficacy of a human EGFR vaccine in preventing LCprogression. These novel findings suggest potential strategies for cancer preventionand therapy.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}