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}
{"title":"Multifunctional Hydrogel Strategies for Myocardial Infarction: From Tissue Repair to Cardiac Regeneration","authors":"Youze Lu, Shuqun Yang, Qiaoling Yang, Weiqiang Huang","doi":"10.1002/adtp.202400383","DOIUrl":"https://doi.org/10.1002/adtp.202400383","url":null,"abstract":"<p>Myocardial infarction (MI) remains the leading cause of death in patients with cardiovascular disease worldwide, with therapeutic approaches predominantly relying on medication, medical device implantation, and organ transplantation, each constrained by inherent limitations. Injectable hydrogels have recently emerged as promising therapeutic tools, noted for their biocompatibility, injectability, and capacity to provide mechanical support crucial for myocardial tissue repair. This review aims to comprehensively explore the interaction between injectable hydrogels and myocardial repair post-infarction. It encompasses recent advancements in various types of injectable hydrogels used in MI therapy, including those modulating microenvironments, conducting electricity, influencing immunomodulation, promoting angiogenesis, and improving ischemia-reperfusion conditions. By synthesizing current research findings, this review facilitates interdisciplinary knowledge integration and the development of effective prognostic indicators for injectable materials.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143116619","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}
Kassandra Koumaki, Salomi Skarmalioraki, Vivian Kosmidou, Lida Krikoni, Maria Goulielmaki, Vassilis Zoumpourlis, Alexander Pintzas, Vassilis L. Souliotis
{"title":"Antitumorigenic Effect of Combination Treatment with BRAF Inhibitor and Cisplatin in Colorectal Cancer In Vitro and In Vivo","authors":"Kassandra Koumaki, Salomi Skarmalioraki, Vivian Kosmidou, Lida Krikoni, Maria Goulielmaki, Vassilis Zoumpourlis, Alexander Pintzas, Vassilis L. Souliotis","doi":"10.1002/adtp.202400250","DOIUrl":"https://doi.org/10.1002/adtp.202400250","url":null,"abstract":"<p>In colorectal cancer (CRC), BRAF inhibitor (BRAFi) monotherapy appears ineffective, while cisplatin treatment is associated with adverse effects, drug resistance, and reduced efficacy. Herein, a combinatorial approach is being explored to increase the likelihood of effectively killing colorectal cancer cells. The combined effect of BRAFi (PLX4720, Vemurafenib, Dabrafenib, Encorafenib) and cisplatin treatment is examined in BRAFV600E-mutated (RKO, HT29, Colo-205) and BRAFwt (Caco-2) cell lines, as well as in mouse xenografts of RKO cells. Following cisplatin-only treatment, all cell lines show accumulation within subG1 (apoptotic cells) and G2/M phases, as well as phosphorylation of ERK1/2 and H2AX. Following BRAFi-only treatment, BRAFV600E-mutated cells show accumulation within G0/G1 phase, reduced distribution in the S and G2/M phases, inhibition of ERK1/2 phosphorylation, and increased phosphorylation of H2AX. Combined BRAFi and cisplatin treatment synergistically decrease RKO cells viability, reduce phosphorylation of ERK1/2, and increase phosphorylation of H2AX. Importantly, in mouse xenografts of RKO cells, combined PLX4720 and cisplatin treatment show superior therapeutic potential than each monotherapy (<i>P</i> < 0.001). Taken together, in in vitro and in vivo preclinical models, BRAFi and cisplatin combined treatment has shown an improved antitumor effect, rendering it a potential anticancer treatment strategy for BRAF-mutant colon cancer patients.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143115872","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}
Kaavian Shariati, Meiwand Bedar, Kelly X. Huang, Shahrzad Moghadam, Sarah Mirzaie, Jonnby S. LaGuardia, Wei Chen, Youngnam Kang, Xiaoyan Ren, Justine C. Lee
{"title":"Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration","authors":"Kaavian Shariati, Meiwand Bedar, Kelly X. Huang, Shahrzad Moghadam, Sarah Mirzaie, Jonnby S. LaGuardia, Wei Chen, Youngnam Kang, Xiaoyan Ren, Justine C. Lee","doi":"10.1002/adtp.202400296","DOIUrl":"10.1002/adtp.202400296","url":null,"abstract":"<p>Tissue regeneration involves dynamic dialogue between and among different cells and their surrounding matrices. Bone regeneration is specifically governed by reciprocity between osteoblasts and osteoclasts within the bone microenvironment. Osteoclast-directed resorption and osteoblast-directed formation of bone are essential to bone remodeling, and the crosstalk between these cells is vital to curating a sequence of events that culminate in the creation of bone tissue. Among bone biomaterial strategies, many have investigated the use of different material cues to direct the development and activity of osteoblasts. However, less attention has been given to exploring features that similarly target osteoclast formation and activity, with even fewer strategies demonstrating or integrating biomaterial-directed modulation of osteoblast-osteoclast coupling. This review aims to describe various biomaterial cues demonstrated to influence osteoclastogenesis and osteoclast function, emphasizing those that enhance a material construct's ability to achieve bone healing and regeneration. Additionally discussed are approaches that influence the communication between osteoclasts and osteoblasts, particularly in a manner that takes advantage of their coupling. Deepening the understanding of how biomaterial cues may dictate osteoclast differentiation, function, and influence on the microenvironment may enable the realization of bone-replacement interventions with enhanced integrative and regenerative capacities.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045445","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":"Recent Therapeutic Advancements for Gaucher Disease","authors":"Lipi Pradhan, Sumit Manna, Pragya Pragya, Sudip Mukherjee","doi":"10.1002/adtp.202400292","DOIUrl":"https://doi.org/10.1002/adtp.202400292","url":null,"abstract":"<p>Gaucher Disease (GD) is a well-known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits a range of clinical manifestations, each with unique symptoms and severity levels. This review explores the genetic foundations of GD, highlighting the significance of Glucocerebrosidase (GCase) deficiency, resulting in the skeletal complications associated with GD, such as osteonecrosis, fractures, and bone pain, all of which significantly negatively influence the quality of life for patients. Over 700 mutations in the GBA1 gene are found to cause variations in gene expression in GD, indicating the disease's complexity and the need for continued research. Early diagnosis and prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, genetic testing, and clinical symptoms. Treatment strategies like enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have advanced, but issues like high costs and invasiveness still exist. This review focuses on novel therapeutic approaches that show promise in treating GD, including gene and cell-based therapies, pharmacological chaperone therapy (PCT), and drug delivery via nanoparticles. Finally, discussions on current clinical trials, limitations of the advanced therapies, and future scope are summarized.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143115467","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":"Dimethyl Fumarate Augments Anticancer Activity of Ångstrom Silver Particles in Myeloma Cells through NRF2 Activation","authors":"Ben Wu, Zhen-Xing Wang, Hui Xie, Ping-Li Xie","doi":"10.1002/adtp.202400363","DOIUrl":"https://doi.org/10.1002/adtp.202400363","url":null,"abstract":"<p>Multiple myeloma (MM) is an incurable hematological malignancy characterized by relapse and drug resistance. This study investigates the potential of angstrom-scale silver particles (F-AgÅPs) to selectively target and eliminate MM cells, focusing on their susceptibility and underlying mechanisms. F-AgÅPs are synthesized using a pure physical high-efficiency evaporation-condensation method and coated with fructose, and their cytotoxic effects on MM cell lines are evaluated through cell viability assays and flow cytometry. Reactive oxygen species (ROS) levels are measured to elucidate oxidative stress, while the role of nuclear factor erythroid 2-related factor 2 (NRF2) is examined via western blotting and quantitative PCR. In vivo, the therapeutic potential of F-AgÅPs is assessed using a MM xenograft mouse model. F-AgÅPs exhibited significant cytotoxicity in MM cells at low concentrations, with higher ROS levels leading to oxidative damage and NRF2 accumulation. This effect is mitigated by the ROS scavenger N-acetyl-l-cysteine. Additionally, the NRF2 activator dimethyl fumarate (DMF) enhanced F-AgÅPs-induced cytotoxicity in vitro and suppressed myeloma growth in vivo. These findings suggest that combining DMF with F-AgÅPs is a promising therapeutic strategy for MM, effectively targeting ROS-induced oxidative damage through NRF2 activation.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114868","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":"Transdermal Delivery of Superoxide Dismutase Using Polymeric Microneedle Patches to Inhibit Skin Aging","authors":"Yongli Chen, Yanyan Zhang, Kaimin Zhang, Lihong Gu, Liang Dong, Ken Oakes, Xu Zhang","doi":"10.1002/adtp.202400159","DOIUrl":"https://doi.org/10.1002/adtp.202400159","url":null,"abstract":"<p>Skin aging is characterized by a deterioration of skin quality over time resulting from physiological changes and oxidative stress (OS). Superoxide dismutase (SOD) is an effective antioxidant enzyme widely used as a food supplement and cosmetic additive to alleviate OS and retard skin aging. However, conventional SOD delivery routes commonly yield unsatisfactory results due to limited stability, compromised bioavailability, and low absorption efficiency in the gastrointestinal (GI) tract. These issues are addressed by developing SOD-encapsulated polymeric microneedle (PMN) patches for efficient transdermal delivery. The use of a highly stable SOD isolated from a hot spring microbe ensures its reactivity throughout PMN fabrication and application. This SOD vehicle demonstrated excellent effectiveness through inhibiting skin-aging and promoting hair growth as validated by extensive in vivo experiments using D-galactose (D-gal) induced aging-mouse model. SOD-PMNs promoted excellent regeneration of hair follicles, increased melanin synthesis, decreased lipid oxidation, and elevated antioxidative capacity of skin tissue. The success in effective transdermal delivery of SOD promises wide applicability in pharmaceutical and cosmetic industries.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868261","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}
Binqing Xue, Yao Yao, Enhui Luo, Duncan James Lessing, Min Guo, Weihua Chu
{"title":"An Integrated Therapeutic Nanoparticles and Quorum Quenching-Based Microneedle Patch for Bacterial-Infected Wound Healing","authors":"Binqing Xue, Yao Yao, Enhui Luo, Duncan James Lessing, Min Guo, Weihua Chu","doi":"10.1002/adtp.202400405","DOIUrl":"https://doi.org/10.1002/adtp.202400405","url":null,"abstract":"<p>Skin injuries leading to drug-resistant bacterial infections remain a significant challenge, posing a threat to human health. There is an urgent necessity to develop wound dressings for the treatment of such injuries. The proceeding study presents the design of a multifunctional microneedle (MNs) patch containing quorum-quenching enzyme and manganese dioxide (MnO<sub>2</sub>) nanoparticles for treating <i>Pseudomonas aeruginosa</i>-infected wounds. In co-culture experiments with <i>P. aeruginosa</i>, the quorum-quenching enzyme significantly reduced the production of virulence factors and inhibited biofilm formation. MnO<sub>2</sub> NPs exhibited excellent scavenging ability against a wide range of free radicals when assayed in in vitro antioxidant assays. Subsequently, soluble hyaluronic acid is chosen as the substrate in order to prepare the MNs patches loaded with quorum quenching enzyme and MnO<sub>2</sub> NPs for wound healing assessment in a <i>P. aeruginosa</i>-infected mouse wound model. Evaluation of wound size and closure rate demonstrated that the patch significantly accelerated wound healing, resulting in shorter healing durations and improved wound closure. Additionally, inflammation-related cytokine levels are reduced, indicating a lower level of inflammation. Tissue section staining shows that treatment with MNs promoted wound epithelialization, collagen deposition, and angiogenesis. The multifunctional MNs patch represents a promising treatment option for drug-resistant bacterial infections in wound management.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114017","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}
Federica Carnevali, Stefania Forciniti, Valentina Onesto, Anna Chiara Siciliano, Helena Iuele, Giuliana Grasso, Anderson Fraga da Cruz, Ilaria Serra, Norma Depalma, Stefano D'Ugo, Prisco Piscitelli, Marcello G. Spampinato, Giuseppe Gigli, Carolina Camargo de Oliveira, Loretta L. del Mercato
{"title":"Advancements in Cancer Research: 3D Models, Single-Cell, and Live-Cell Techniques for Better Insights","authors":"Federica Carnevali, Stefania Forciniti, Valentina Onesto, Anna Chiara Siciliano, Helena Iuele, Giuliana Grasso, Anderson Fraga da Cruz, Ilaria Serra, Norma Depalma, Stefano D'Ugo, Prisco Piscitelli, Marcello G. Spampinato, Giuseppe Gigli, Carolina Camargo de Oliveira, Loretta L. del Mercato","doi":"10.1002/adtp.202400351","DOIUrl":"https://doi.org/10.1002/adtp.202400351","url":null,"abstract":"<p>The present review provides a comprehensive overview of the current state of in vitro cancer studies, focusing on recent advancements and ongoing in cell culture models and analyses techniques. Cancer cells grow in a complex and dynamic environment, interacting with various cellular components, such as stromal cells, cancer-associated fibroblasts, immune cells, and the extracellular matrix (ECM). The ECM provides structural support and unique characteristics essential for tumorigenesis. Accurately modeling this intricate tumor microenvironment and precisely analyzing cell–cell and cell–ECM interactions are crucial for understanding cancer progression and therapeutic responses. Consequently, oncology research is advancing toward a) three-dimensional tumor models, b) single-cell level analyses, and c) live-cell analyses. This review aims to elucidate current knowledge in this field, emphasizing the benefits these innovative approaches offer over traditional two-dimensional models, bulk analyses, and endpoint measurements.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868435","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}