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}
{"title":"An Acellular Platform to Drive Urinary Bladder Tissue Regeneration","authors":"Mitali Kini, Matthew I. Bury, Arun K. Sharma","doi":"10.1002/adtp.202400158","DOIUrl":"10.1002/adtp.202400158","url":null,"abstract":"<p>Impaired bladder compliance secondary to congenital or acquired bladder dysfunction can lead to irreversible kidney damage. This is managed with surgical augmentation utilizing intestinal tissue, which can cause stone formation, infections, and malignant transformation. Co-seeded bone marrow mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSPC) scaffolds (PRS) have been successful in regenerating bladder tissue. However, the acquisition of viable cells is challenging in the clinical setting. Here, the regenerative capacity of human MSC/CD34+ co-cultured total condition media (TCM) is compared to media alone in immune-competent rats augmented with PRS following partial cystectomy. Augmented bladders are instilled with media (control, <i>n</i> = 4) or TCM (<i>n</i> = 5) twice a week for 4 weeks. Regenerated tissue is analyzed for smooth muscle, urothelium, vascular, and peripheral nerve regrowth. Urodynamic (UDS) measures are performed pre- and 4 weeks post-augmentation. The results demonstrate that TCM-instilled grafts have greater muscle content, larger average urothelial widths, higher percent vascularization, and more robust neural infiltration post-augmentation. UDS demonstrates greater percent bladder recovery in the TCM group, indicating functional improvement in bladder storage capacity. This study is the first to propose the use of cell-free TCM as an alternative to traditional cell-seeded scaffolds to promote bladder tissue regeneration.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998407","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":"Repurposing Sertraline for the Treatment of Colorectal Cancer by Blocking Autophagic Flux and Inhibiting Tumor Proliferation (Adv. Therap. 12/2024)","authors":"Leping He, Xijun Guo, Wanrong Wang, Weifeng Xu, Xiaoli Feng, Yuanfeng Fu, Yuxi Tian, Zongmao He, Sulan Luo, Jiaolin Bao, Ren-Bo Ding","doi":"10.1002/adtp.202470028","DOIUrl":"https://doi.org/10.1002/adtp.202470028","url":null,"abstract":"<p>Autophagy facilitates the degradation and recycling of nonfunctional proteins and organelles in autolysosome, which contributes to tumor maintenance. Antidepressant sertraline was found to induce AMPK-mTOR signaling mediated autophagosome accumulation, but block autophagic flux at the stage of autolysosomal degradation, thus suppressing the colorectal cancer survival. The study reports the repurposing of sertraline as an anticancer drug through the mechanism of inhibiting autophagic flux. More details can be found in article 2400199 by Jiaolin Bao, Ren-Bo Ding 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":"7 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202470028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868246","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}
Francesco Bisconti, Beatrice Vilardo, Gaia Corallo, Francesca Scalera, Giuseppe Gigli, Annalisa Chiocchetti, Alessandro Polini, Francesca Gervaso
{"title":"An Assist for Arthritis Studies: A 3D Cell Culture of Human Fibroblast-Like Synoviocytes by Encapsulation in a Chitosan-Based Hydrogel (Adv. Therap. 12/2024)","authors":"Francesco Bisconti, Beatrice Vilardo, Gaia Corallo, Francesca Scalera, Giuseppe Gigli, Annalisa Chiocchetti, Alessandro Polini, Francesca Gervaso","doi":"10.1002/adtp.202470027","DOIUrl":"https://doi.org/10.1002/adtp.202470027","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a complex autoimmune disorder with poorly understood mechanisms. In the article 2400166, Alessandro Polini, Francesca Gervaso, and co-workers introduce a chitosan-based hydrogel for 3D culture of fibroblast-like synoviocytes, offering new insights into RA. The cover image highlights the hydrogel's cellular structure. Cover designed by: Francesco Bisconti, Jacopo Tarantino, Francesca Gervaso, Alessandro Polini.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202470027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868245","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}
Lívia Maria Coelho de Carvalho Moreira, Antônia Carla de Jesus Oliveira, Luíse Lopes Chaves, Mônica Felts de La Rocca Soares, José Lamartine Soares-Sobrinho
{"title":"From Challenges to Solution: The Evolving Landscape of Leprosy Management (Adv. Therap. 12/2024)","authors":"Lívia Maria Coelho de Carvalho Moreira, Antônia Carla de Jesus Oliveira, Luíse Lopes Chaves, Mônica Felts de La Rocca Soares, José Lamartine Soares-Sobrinho","doi":"10.1002/adtp.202470030","DOIUrl":"https://doi.org/10.1002/adtp.202470030","url":null,"abstract":"<p><i>Mycobacterium leprae</i> infects macrophages and Schwann cells, causing leprosy. Current treatments, though effective, have many side effects. Developing safer therapies, such as drug delivery systems and advances in immunoprophylaxis, can improve efficacy and patient quality of life. More details can be found in article 2400249 by José Lamartine Soares-Sobrinho 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":"7 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202470030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868247","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}
Colin McGuckin, Nico Forraz, Clément Milet, Mathieu Lacroix, Yordan Sbirkov, Victoria Sarafian, Caroline Ebel, Anita Spindler, Véronique Koerper, Eric Quéméneur, Jean-Marc Balloul, Philippe Erbs
{"title":"Stable Biotherapeutic Penetration Screening in Critically Small Colorectal Metastatic Cancer Biopsies Allows for Oncolytic Virus-Delivered Chemotherapeutic Response Assessment through 3D Bioprinted Organoid Expansion","authors":"Colin McGuckin, Nico Forraz, Clément Milet, Mathieu Lacroix, Yordan Sbirkov, Victoria Sarafian, Caroline Ebel, Anita Spindler, Véronique Koerper, Eric Quéméneur, Jean-Marc Balloul, Philippe Erbs","doi":"10.1002/adtp.202400221","DOIUrl":"https://doi.org/10.1002/adtp.202400221","url":null,"abstract":"<p>Oncolytic viral-delivered chemotherapeutics have exciting potential for metastatic cancer therapies, including colorectal cancer, but require advanced screening systems for better patient prediction. We optimized primary metastatic colorectal tumor processing and 3D (3-dimensional) bioprinted tumors to prove efficacy as long-term screening systems. Normally, this time period would use animals, but we show it is possible to gain useful data in vitro before preclinical stages, to reduce animal modeling and give better clinical trial predictions. Liver tumors were collected from 12 colorectal cancer patients, evaluated for expansion, 3D bioprinted, and tested for ability to create long-term organoid models with screening of oncolytic viral-loaded FCU1 enzyme conversion of 5-fluorocytosine (5-FC) into the highly toxic 5-fluorouracil (5-FU). Donated tumor size was the limiting factor. 75% of patients could be used for screening of viral delivery. Response between patients was overall positive, with good secondary tumor development, outer active cellular content and inner necrotic core. Oncolytic challenge shows good screening potential and cellular targeting, demonstrating an added bystander effect, optimizing the low-dose. Stable long-term metastatic organoid models were made, lasting many months, with potential for retesting rather than one-off analysis. Oncolytic virus-delivered chemotherapy is promising and warrants further investigation for metastatic colorectal cancers.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111503","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}
Sara A. Strickland, Luke A. Fourroux, McKenna M. McKay, Dimitri Pappas
{"title":"Protein-Derived Carbon Dots: Effects of Synthesis Parameters on Retained Protein Function","authors":"Sara A. Strickland, Luke A. Fourroux, McKenna M. McKay, Dimitri Pappas","doi":"10.1002/adtp.202400366","DOIUrl":"https://doi.org/10.1002/adtp.202400366","url":null,"abstract":"<p>Novel-protein-derived carbon dots have recently been reported with high biocompatibility, superior spatial resolution, photobleaching resistance, customizability, and no post-synthesis conjugation requirement. These nanoparticles bring new capabilities in bioimaging and targeted therapeutics. Protein-based carbon dots contain a carbon core and surface groups from the protein that can retain molecular recognition properties. In this work, a systematic study of synthesis conditions to tune nanoparticle protein function is presented. Bovine serum albumin is used as the model protein to simulate what synthesis parameter alterations yield valuable changes to nanoparticles such as red-shifted photoluminescence, specific size distribution, and surface chemistry functionalization. The dissociation constant, K<sub>D</sub> is also calculated, for model BSA-derived NPs and simulated the 1:1 protein-ligand binding at equilibrium. It is found that increased temperatures generally led to higher quantum yields and more red-shifted CDs believed to be due to larger diameters, while nitrogen doping decreased. However, when using microwave radiation, generally NPs are larger and has a 2.5–4.4% increase in nitrogen, resulting in the most red-shifted and highest quantum yield samples. Oven samples possessed 1.6–17.5x lower K<sub>D</sub> compared to microwave samples. Understanding the effects of these parameters on CD characteristics enables scientists to rationally design CDs properties for specific applications.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118392","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":"Novel Use of Magnesium Hydride to Prevent Peritoneal Adhesions by Regulating Inflammation and Oxidative Stress","authors":"Chuchen Gong, Bohui Li, Yajie Wang, Pei Wang, Qianyin Xie, Enze Liu, Jinchen Fan, Mingsong Wang, Xiansong Wang, Guangyu Ji","doi":"10.1002/adtp.202400319","DOIUrl":"https://doi.org/10.1002/adtp.202400319","url":null,"abstract":"<p>Peritoneal adhesions (PAs) represent a significant clinical challenge, primarily arising from excessive post-surgical inflammation, which leads to the deposition of fibrin and extracellular matrix, forming adhesive bands that can cause severe complications such as intestinal obstruction and infertility. Current therapeutic options offer limited efficacy in preventing or treating PAs, highlighting the need for new strategies. To address this issue, magnesium hydride (MgH₂) microparticles capable are developed of stable hydrogen (H₂) storage and controlled release to regulate inflammation and promote tissue regeneration. The antioxidant properties, inflammation modulation, and H₂ release profile of MgH₂ are evaluated in vitro, while its anti-adhesion, angiogenic, and regenerative effects are assessed in vivo using postoperative rat models. These findings demonstrate that MgH₂ significantly mitigates inflammatory dysregulation, reduces oxidative stress, and effectively prevents peritoneal adhesion formation at wound sites. These results suggest that MgH₂ offers a promising therapeutic approach for preventing PAs and supporting beneficial tissue regeneration, presenting a potential clinical solution for postoperative adhesion management.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118391","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}