Yapıncak Goncu, Gokçe Mehmet Ay, Aykut Kucukbas, Fatih Kar, Cansu Ozbayer, Ezgi Kar, Hakan Senturk
{"title":"Injectable Boron Nitride-Hyaluronic Acid Hybrid Hydrogels to Facilitate Joint Motion: Mechanical and Tribological Characterization","authors":"Yapıncak Goncu, Gokçe Mehmet Ay, Aykut Kucukbas, Fatih Kar, Cansu Ozbayer, Ezgi Kar, Hakan Senturk","doi":"10.1002/adtp.202400196","DOIUrl":"10.1002/adtp.202400196","url":null,"abstract":"<p>Hexagonal boron nitride (hBN) is used as an additive in engineering applications such as polymers, ceramics, and coatings because of its anti-wear and lubrication performance. It has a high potential as a biomaterial, but it has not been evaluated to facilitate joint motion with its lubricating properties until now. In this study, the hypothesis that boron nitride nanoparticles (BNPs) and nanosheets (BNNSs) can facilitate movement in the joint region is evaluated for the first time. Hyaluronic acid-based hybrid hydrogels are designed to transport BN particles to the target area and pin-on-disc tests on cartilage pins paired with glass disks are conducted to determine the validity of the proposed hypothesis. The injectability, mechanical properties, and friction coefficients of hydrogels with the addition of increasing proportions of different hBN morphologies are monitored. As a result, hyaluronic acid has been found to be a suitable carrier for the injectability of boron nitride in biomedical applications. The amount and morphology of boron nitride are observed as two important parameters. A significant decrease in the friction coefficient (18.9%) is observed in the BNNS-doped hybrid hydrogel compared to the virgin hydrogel. hBN can be considered as a new therapeutic agent with the potential to facilitate joint mobility.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744625","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":"Estrogen-Related Receptor Gamma (ERRγ) as Biomarker and Novel Target for Therapeutic Intervention on Cancer: A Review","authors":"Priyanka Upadhyay, Ridhima Goel, Deepak Gulwani, Vijaya Sarangthem, Thoudam Debraj Singh","doi":"10.1002/adtp.202400192","DOIUrl":"10.1002/adtp.202400192","url":null,"abstract":"<p>Estrogen-related receptors (ERRs), genes similar to estrogen receptors, are identified as hormone-responsive systems associated with the ERR subfamily. These hormone-responsive systems facilitate oncometabolic programs to nourish cancer cell growth, a central node at the interface of cellular energy metabolism and cancer. Several independent studies have implicated ERR isoforms like ERRα, ERRβ, and ERRγ in the pathways of cancer development and progression. The construction of tissue-specific ERR transgenic or knockout mice and the application of synthetic ligands have precisely indicated the critical and diverse role of ERRγ than other isoforms. ERRγ, plays a critical and diverse role, enabling switching metabolism to oncometabolism in favor of cancer cells, making it a “hot target” in cancer therapy. ERRγ expression is correlated with the clinical status of diverse cancer types and various cancer tissue treatments. The dual feature of ERRγ raises interest in understanding its biogenesis and function in different tissues. This review aims to describe the structural organization of ERRs, their central occupancy at the interface of cancer and metabolism, and their biogenesis and expression profile across different cancers. It concludes that ERRγ has potential as a clinical marker in cancer prognosis and a novel non-conventional therapeutic target.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754016","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}
Chang Qu, Xinyue Shao, Yuling Li, Ran Jia, Jinping Wang, Hailong An
{"title":"Electro-Responsive Nanotherapeutics for Tumor Therapy by Manipulating Accidental and Regulated Cell Death Pathway","authors":"Chang Qu, Xinyue Shao, Yuling Li, Ran Jia, Jinping Wang, Hailong An","doi":"10.1002/adtp.202400160","DOIUrl":"10.1002/adtp.202400160","url":null,"abstract":"<p>In recent years, the development of electro-responsive nanomaterials has attracted significant attention in the field of cancer therapy. By incorporating these smart nanomaterials into therapeutic approaches, researchers explored many novel strategies to selectively induce cell death in tumor tissues while minimizing damage to healthy cells. This comprehensive review highlights the current state of research on electro-responsive nanomaterials and their ability to manipulate accidental and regulated cell death for effective tumor therapy. The scope includes the biomechanisms of electro-responsive nanotherapeutics inducing tumor cell death and their various detailed applications in cancer treatments. The review is concluded with deliberations on the key challenges and future outlooks of electro-responsive nanotherapeutics for tumor therapy.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746319","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":"RNA Encapsulation in Metal–Organic Frameworks for Targeting Cancer-Causing Genes","authors":"Meemansha Mishra, Tapan Dey, Mallya Mishra, Isha Chauhan, Saikat Dutta","doi":"10.1002/adtp.202400144","DOIUrl":"10.1002/adtp.202400144","url":null,"abstract":"<p>A rapid emergence of small interfering ribonucleic acid (siRNA) is witnessed as a powerful tool in gene therapy for suppressing gene expression. Since highly porous metal-organic frameworks (MOFs) are fragile and inefficient with non-specific gene delivery techniques, developing strategies use them to encapsulate unmodified natural siRNA from enzymatic degradation. MOFs with high nucleic acid binding affinity are ideal for encapsulating siRNAs in cancer therapy, bypassing circulation time and non-specificity. To knock down Plk1gene, tumor cell membranes can hide Plk1 siRNA-containing (Zeolitic Imidazolate framework) ZIF-8 nanoparticles. For tumor suppression MOF-promoted lysosome siRNA release, cell membrane coating, and PLK1 silencing are employed. Lysosomes attack cancer by delivering miRNA to targeted cells. Single-stranded miRNA, two-stranded siRNA. Despite their different sources, structures, modes of action, and biological activities, miRNA and siRNA regulate gene expression. SIRNA blocks genes more accurately than miRNA, which regulates larger genes. SiRNA-MOF integration in vitro results in a maximum of 27% consistent gene silencing during endocytic absorption. Cofactor-encapsulated MOF-internalized siRNA kills enzymes. A universal siRNA delivery for a specific genetic sequence with personalized therapeutic potential contrasts with multi-route cancer drugs. SiRNAs cleave long-stranded RNAs coding for specific genes, allowing biocompatible MOFs to encapsulate macromolecules and protect them from injury.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 9","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744626","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}
Lin-Jie Liu, Hong Li, Chun-Yuan Chen, Ting-Ting Li, Biao Deng, Zhu Liang, Jia Liu
{"title":"Efficacy Evaluation of Adjuvant Therapeutic Drugs Against Early and Middle Stage Non-Small Cell Lung Cancer Organoids","authors":"Lin-Jie Liu, Hong Li, Chun-Yuan Chen, Ting-Ting Li, Biao Deng, Zhu Liang, Jia Liu","doi":"10.1002/adtp.202400163","DOIUrl":"10.1002/adtp.202400163","url":null,"abstract":"<p>30–55% post-surgical recurrent rate of early and middle stage non-small cell lung cancer (e/mNSCLC) suggests the need of adjuvant therapy. The e/mNSCLC derived organoids (e/mNSCLCOs)-based efficacy evaluation of the proposed regimens may improve clinical benefits for e/mNSCLC patients. The e/mNSCLCOs are established from 33 IA-IIIB resectable non-small cell lung cancer (NSCLC) patients without systemic antitumor therapy via optimized 3D culture, of which six with epidermal growth factor receptor (EGFR) mutation. Immunohistochemical staining is employed to ascertain the maintenance of biomarker expression patterns of e/mNSCLCOs with that of their parental tumors. The e/mNSCLCOs are treated with six conventional anti-NSCLC chemotherapeutic regimens, respectively. Calcein-AM/PI cell viability/cytotoxicity assay and EdU cell proliferation test reveal that the platinum-based chemotherapeutic or mono-chemotherapeutic regimens are generally ineffective to e/mNSCLCOs because of their high IC<sub>50</sub> values. Non-platinum gemcitabine combined with vinorelbine achieve better anti-e/mNSCLCOs outcome in terms of suppressed cell proliferation and 51.6–65.8% of intra-organoid cell death. The 6 e/mNSCLCOs with EGFR mutations are sensitive to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in drug selective patterns. The low efficacy of conventional anti-NSCLC drugs to e/mNSCLCOs suggests the necessity to explore alternative approaches for better adjuvant management of e/mNSCLC patients.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746321","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":"Calixarene-Guest Complexes: The Next Innovation in Delivery of Drugs and Biologics","authors":"Sheetal Muley, Hozefa Dhila, Meghana Gote","doi":"10.1002/adtp.202400207","DOIUrl":"10.1002/adtp.202400207","url":null,"abstract":"<p>Calixarenes are third generation of macrocyclic molecules with excellent biocompatibility currently being researched extensively for their diverse potential as therapeutic candidates and for delivery of drugs and biologics. This review discusses the unique structural features which allow them to selectively bind to a wide variety of guest molecules within their hydrophobic cavity, as well as complex with other molecules on their upper and lower rims to enable their application for encapsulation of drugs for targeted and controlled release, molecular carriers for antigens and nucleic acids, and as biomedical sensors. The calixarenes’ unique host–guest chemistry enables encapsulation of lipophilic drugs in the latter's cavity, while the head groups and side chains on the upper and lower rim can be functionalized readily with various targeting moieties as peptides and biological ligands which specifically recognize and bind to cancer cells via surface receptors. The design of calixarene constructs help incorporation of multiple functionalities into a single platform. This active targeting approach enhances the accumulation of the drug at the tumor site while reducing its distribution in healthy tissues, thereby minimizing side effects. Ongoing research in exploration and optimization of calixarenes for application as targeted drug and gene delivery agents has been discussed.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746320","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":"Designer Solvents for Pharmaceutics: Role of Ionic Liquids/ Deep Eutectic Solvents in Pharmaceutical Formulations","authors":"Diksha Dhiman, Munirah Alhammadi, Hanseung Kim, Reddicherla Umapathi, Yun Suk Huh, Pannuru Venkatesu","doi":"10.1002/adtp.202400090","DOIUrl":"10.1002/adtp.202400090","url":null,"abstract":"<p>The design of biologic and synthetic drugs in the pharmaceutical industry is facing three key challenges, namely, ensuring bioavailability, solubility, and stability. Ionic liquids (ILs) and deep eutectic solvents (DESs), classified as designer solvents, have emerged as excellent solvents for improving the permeability and stability of biotherapeutic drugs. Moreover, they have shown remarkable solubilizing effects for synthetic drugs, particularly in solubilizing active pharmaceutical ingredients (API), and are known as eco-friendly solvents. Thus, in this review, the development of designer formulations in pharmaceutical industries is reported, and the underlying strategies for designing the most efficient formulations for both biotherapeutics and synthetic drugs are examined.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649586","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}
Huiwen Pang, Zhi Qu, Vinod Kumar, Yinuo Wang, Youzhi Wu, Min-Hsuan Lin, David Harrich, Felicity Y. Han
{"title":"Novel Delivery Systems for Oral Administration of Enfuvirtide: New Treatment Options for HIV/AIDS","authors":"Huiwen Pang, Zhi Qu, Vinod Kumar, Yinuo Wang, Youzhi Wu, Min-Hsuan Lin, David Harrich, Felicity Y. Han","doi":"10.1002/adtp.202300439","DOIUrl":"10.1002/adtp.202300439","url":null,"abstract":"<p>Enfuvirtide (T-20) is a synthetic peptide fusion inhibitor for the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). However, the peptide nature limits a wider application of T-20 with subcutaneous injection (Fuzeon) the only available formulation. In this groundbreaking study, it is sought to overcome this limitation by employing poly lactic-co-glycolic acid (PLGA) and alginate to create novel oral delivery systems for T-20. Remarkably, this investigation marks the first instance of assessing the efficacy of oral delivery systems in mice. Notably, both the PLGA and alginate formulations exhibit the capability to sustain T-20 release, maintaining detectable levels in the bloodstream of mice for over 24 h after a single dose. By venturing into the realm of oral T-20 delivery, this study opens avenues for the prospective development of oral formulations of T-20, potentially leading to their evaluation in clinical trials.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202300439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141650509","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":"Effect of APOE ɛ4 Status on Brain Amyloid-β and Cognitive Function in Amnestic and Nonamnestic Mild Cognitive Impairment: A [18F] Florbetapir PET-CT Study","authors":"Mengjie Wang, Zhengwei Zhang, Ying Wang, Lin Huang, Qi Huang, Shuhua Ren, Luojun Qian, Ruiqing Ni, Qihao Guo, Yihui Guan, Fang Xie","doi":"10.1002/adtp.202400008","DOIUrl":"10.1002/adtp.202400008","url":null,"abstract":"<p>Mild cognitive impairment (MCI) is recognized as a predementia syndrome caused by multiple etiologies and nonmemory symptoms in MCI have recently gained increasing attention. However, the pattern of Aβ deposition and the effect of APOE (apolipoprotein E, APOE) ε4 on cognitive impairment in amnestic MCI (aMCI) and nonamnestic MCI (naMCI) patients has not been demonstrated. In this work, the amyloid-β (Aβ) load by [<sup>18</sup>F]florbetapir PET imaging and cognitive performance is compared by comprehensive neuropsychological scales in participants with different MCI types or different APOE ε4 carriage status. According to the Aβ positivity and results of voxel-wise analysis, higher Aβ loads are observed in aMCI patients than naMCI patients, especially aMCI patients with APOE ε4. Additionally, it is observed that memory domain Z scores show a strong negative correlation with global florbetapir SUVR in the aMCI group (<i>r</i> = – 0.352, <i>p</i> < 0.001) but not in the naMCI group (<i>r</i> = –0.016, <i>p</i> = 0.924). Moreover, this correlation is independent of APOE e4 carriage status. This study aims to identify high-risk groups at an early stage of AD(Alzheimer's Disease, AD) through cognitive performance and APOE ε4 carrier status, which can be important for guiding clinical intervention trials.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141650645","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":"A Facile Approach to Producing Liposomal J-Aggregates of Indocyanine Green with Diagnostic and Therapeutic Potential","authors":"Noah B Stern, Binita Shrestha, Tyrone Porter","doi":"10.1002/adtp.202400042","DOIUrl":"10.1002/adtp.202400042","url":null,"abstract":"<p>Liposomal J-Aggregates of Indocyanine Green (L-JA) can serve as a biocompatible and biodegradable nanoparticle for photoacoustic imaging (PAI) and photothermal therapy (PTT). When compared to monomeric indocyanine green (IcG), L-JA is characterized by longer circulation, improved photostability, elevated absorption at longer wavelengths, and increased photoacoustic signal generation. However, the documented methods for the production of L-JA vary widely. An approach to efficiently form IcG J-aggregates (IcG-JA) directly in liposomes at elevated temperatures is developed. Aggregating within fully formed liposomes ensures particle uniformity and allows for control of J-aggregate size. L-JA has unique properties compared to IcG. L-JA provides significant contrast enhancement in photoacoustic images for up to 24 h after injection, while IcG and unencapsulated IcG-JA are cleared within an hour. L-JA allows for more accurate photoacoustic-based blood oxygen saturation (sO<sub>2</sub>) estimation and particle tracking compared to IcG. Furthermore, photothermal heating of L-JA with an 852 nm laser is demonstrated to be more effective at lower laser powers than conventional 808 nm lasers for the first time. The presented technique offers an avenue for formulating a multi-faceted contrast agent for photoacoustic imaging and photothermal therapy that offers significant advantages over other conventional agents.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609980","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}