{"title":"Copper and Iron-Based Metal-Organic Frameworks for Synergistic Cancer Phototherapies: Recent Advances, Challenges, and Future Prospects","authors":"Kayalvizhi Samuvel Muthiah, Kalaiarasu Lakshminarayanan, Yu Chien Lin, Udesh Dhawan, Loganathan Rangasamy, Ren-Jei Chung","doi":"10.1002/adtp.202500117","DOIUrl":"https://doi.org/10.1002/adtp.202500117","url":null,"abstract":"<p>Current treatments for cancer such as surgery, chemotherapy, radiotherapy, and chemodynamic therapy often exhibit poor efficacy and severe side effects; this, cancer remains a major global health challenge. In the ongoing exploration of therapeutic strategies with improved outcomes and reduced adverse effects, phototherapies (PTs), including photothermal (PTT) and photodynamic therapy (PDT), are gaining attention due to their non-invasive and targeted nature, resulting in reduced side effects. However, further material optimizations are needed to enhance PT performance. Metal-organic frameworks (MOFs) have emerged as promising PTT/PDT nanoplatforms due to their tunable structures, high surface area, and ability to host photoactive agents. Their porous architecture facilitates efficient photosensitizer encapsulation and promotes light-induced thermal effects, improving therapeutic stability and efficacy. The therapeutic potential of MOFs is further enhanced when combined with multiple treatment modalities. This review focuses on the roles of Fe/Cu-based MOFs in PTs, their synthesis, underlying mechanisms in PTT/PDT, and recent design advancements. It also summarizes the progress in Cu/Fe-MOF nanocomposite development over the past 5 years, from construction to synergistic applications. These insights can inform future efforts in the clinical translation of Cu/Fe-MOFs in cancer theranostics.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284749","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}
Qi Tan, Yuwei Hu, Bo Wang, Songwei Tan, Yang Guan, Li Zhou, Qing Tang
{"title":"HPG-PLGA Nanoparticles for Enhanced Baicalin Delivery in Ulcerative Colitis Treatment","authors":"Qi Tan, Yuwei Hu, Bo Wang, Songwei Tan, Yang Guan, Li Zhou, Qing Tang","doi":"10.1002/adtp.202500056","DOIUrl":"https://doi.org/10.1002/adtp.202500056","url":null,"abstract":"<p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a need for more effective and less invasive treatment options. This study aimed to develop a targeted drug delivery system using hyperbranched polyglycidylglycerol-poly(lactic acid)-hydroxyacetic acid (HPG-PLGA)nanoparticles (NPs) loaded with baicalin (BN), a flavonoid with potent anti-inflammatory properties, to enhance therapeutic efficacy in UC. HPG-PLGA NPs are synthesized, characterized, and loaded with BN. The particle size, polydispersity index (PDI), encapsulation efficiency, and in vitro release profile of the NPs are evaluated. The in vivo biodistribution and therapeutic efficacy of the NPs are assessed in a dextran sulfate sodium-induced UC mouse model. The synthesized HPG-PLGA NPs demonstrated good stability and a controlled release of BN. In vivo studies showed significant accumulation of NPs in the inflamed colon, with a subsequent reduction in disease activity and inflammation markers. The treatment group exhibited lower levels of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 compared to the model group, indicating effective alleviation of inflammation. Furthermore, the NPs showed no significant toxicity to major organs. This study provides a promising approach for the development of targeted UC treatments, offering a potential clinical application by enhancing the bioavailability and specificity of BN to inflammatory sites.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284789","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":"Injectable Hydrogel of Thiol Mediated Photopolymer Grafted Polyurethane as Controlled Drug Delivery Vehicle for Melanoma Treatment","authors":"Amita Santra, Sudipta Bauri, Alaka T Panicker, Souvik Debnath, Kaushik Chatterjee, Pralay Maiti","doi":"10.1002/adtp.202500251","DOIUrl":"https://doi.org/10.1002/adtp.202500251","url":null,"abstract":"<p>Ultraviolet (UV) photocurable bisphenol A-glycerolate dimethacrylate (bis-GMA) and pentaerythritol tetrakis(3-mercaptopropionate) (PETMP)-based copolymers have been synthesized usingthiol-ene chemistry with tailorable size. This copolymer was further grafted with polyurethane (PU) through in-situ polymerization using its diisocyanate chain ends to balance its hydrophobicity for controlled drug delivery. Characterization by various spectroscopic techniques confirmed the structure, shape, and size of the synthesized polymer; thermal analysis revealed higher glass transition temperatures, and enhanced thermal stability. Rheological analysis showed improved strength and favourable flow behaviour. UV–Vis and FTIR demonstrated strong polymer–drug interactions, correlating with the sustained drug release observed, in contrast to pure PU and copolymer. Drug-loaded graft copolymer was incorporated into 3D-printed scaffolds, supporting in vitro cell growth for 7 days, confirming biocompatibility. An in vivo melanoma mouse model study showed considerable tumor reduction without any side effects, unlike traditional chemotherapy, owing to localized hydrogel injection beneath the tumor for sustained release. Overall, this injectable hydrogel, derived from the synthesized graft copolymer, offers a thermally stable, mechanically robust, biocompatible, and a viable drug delivery system for cancer therapy, with reduced toxicity and high therapeutic potential.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284689","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}
Md Kowsar Alam, Lu Yanjun, Bee Luan Khoo, Tongxu Si, Heng Zou, Mengsu Yang
{"title":"Heterogeneity Landscape of Circulating Tumor Cells in Clinical Utility","authors":"Md Kowsar Alam, Lu Yanjun, Bee Luan Khoo, Tongxu Si, Heng Zou, Mengsu Yang","doi":"10.1002/adtp.202400438","DOIUrl":"https://doi.org/10.1002/adtp.202400438","url":null,"abstract":"<p>Circulating tumor cells (CTCs) are seeds for metastasis and are key elements of liquid biopsies. Despite their small numbers, CTCs exhibit significant heterogeneity in terms of quantity, surface markers, and physical characteristics. This diversity poses challenges for the accurate detection and analysis of CTCs, which are essential for precise diagnosis and clinical decision-making. Additionally, spatiotemporal changes in physiological systems and the presence of circulating tumor endothelial cells (CTECs) contribute to fluctuations in the numbers and properties of both individual and clustered CTCs, affecting molecular changes and metastatic potential. It is imperative to carefully consider these variations during blood sampling, CTC detection, result analysis, and treatment planning to ensure successful clinical outcomes. The review has explored various aspects of CTC heterogeneity, emphasizing additional factors that may impact the reliability of CTC analyses and their clinical relevance for patient care. Furthermore, insights are offered to enhance the understanding of CTC heterogeneity in the context of precision diagnosis and clinical management.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284691","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}
Yerim Lee, Wanling Wong, Theresa Seah, Dionis Yew, Cyrus W. Beh
{"title":"Non-Viral Manufacturing of Cellular Immunotherapy Using Simple Mechanical Transfection Device","authors":"Yerim Lee, Wanling Wong, Theresa Seah, Dionis Yew, Cyrus W. Beh","doi":"10.1002/adtp.202500094","DOIUrl":"https://doi.org/10.1002/adtp.202500094","url":null,"abstract":"<p>In recent years, cellular immunotherapies, such as chimeric antigen receptor T (CAR-T) therapy, have emerged as promising treatment options for cancer, demonstrating particularly strong efficacy against liquid tumors. By introducing tumor-targeting CAR genes into patient immune cells ex vivo and reintroducing the modified cells into the patient, tumor cells expressing specific surface markers can be selectively killed. However, existing virus-based methods for producing cellular products are plagued by high costs, which seriously limit their adoption. In this paper, the development of a mechanical transfection device is described, which passes cells through micron-sized pores and is capable of delivering different molecules into cells. The effects of parameters such as pore size, flow rate, and payload concentration on transfection efficiency are studied and used to inform a standard transfection protocol. Finally, the delivery of CAR-encoding mRNA into primary T-cells is demonstrated to manufacture CAR-T cells, which secrete IFN-γ and TNF-α in an antigen-specific manner. As the method is developed from the outset to be easily deployable and scalable, it is envisioned that it will be able to impact cell manufacturing in the near future.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284692","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":"Cytokine Engineering Approaches for Regenerative Medicine","authors":"Shiyi Li, Wenhao You, Mikaël M. Martino","doi":"10.1002/adtp.202500103","DOIUrl":"10.1002/adtp.202500103","url":null,"abstract":"<p>Cytokines are central in orchestrating immune responses during tissue repair and regeneration, making them attractive candidates for regenerative medicine. However, their pleiotropic effects, short half-life, and poor biodistribution have limited their clinical translation. Advances in protein engineering have enabled the design of modified cytokines with enhanced stability, receptor selectivity, and tissue-targeting capabilities, offering new therapeutic opportunities for modulating immune activity and promoting tissue healing. Many of these engineering approaches have been pioneered in cancer immunotherapy, where cytokines are often designed to sustain inflammation and enhance cytotoxic immune responses. In contrast, regenerative medicine usually requires immune resolution, necessitating a distinct and sometimes opposite application of cytokine engineering strategies. This review explores the latest advancements in cytokine engineering for regenerative applications, focusing on strategies to enhance cytokine stability, modulate receptor affinity, improve targeting, and regulate endogenous cytokine signaling. Numerous approaches, highlighting how targeted immune modulation can enhance tissue healing while minimizing fibrosis and chronic inflammation, are discussed. These advances hold great promise for treating chronic wounds, fibrotic diseases, and tissue injuries with limited regenerative capacity, paving the way for precise, effective, and clinically translatable cytokine therapeutics. By adapting principles from cancer immunotherapy, cytokine-based therapies could transform regenerative medicine.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101034","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":"Efficacy and Safety of The Albumin-Bound Paclitaxel Combined with Anti-PD-1 Antibody in Pancreatic Ductal Adenocarcinoma","authors":"Wenjing Hao, Yunxia Wang, Jun Zhang, Weimin Cai","doi":"10.1002/adtp.202500075","DOIUrl":"10.1002/adtp.202500075","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited response to chemotherapy and immune checkpoint inhibitors (ICIs). This study evaluates the efficacy and safety of combining Albumin-Bound Paclitaxel (nab-PTX) with an anti-PD-1 antibody and aims to identify potential biomarkers to optimize therapeutic outcomes. The murine model of PDAC is established by subcutaneously injecting the murine pancreatic cancer cell line Panc02 into C57BL/6J mice. The mice are treated with either an anti-PD-1 antibody, nab-PTX, or nab-PTX plus anti-PD-1 antibody, with untreated mice serving as the control. Tumor growth, immune cell infiltration, cytokine levels, overall survival, organ damage, and gene expression profiles are analyzed. The combination therapy shows superior efficacy compared to nab-PTX and non-inferior efficacy compared to the anti-PD-1 antibody. Moreover, this strategy significantly reduces the risk of irAEs and hyperprogression caused by the anti-PD-1 antibody. In addition, screening identifies <i>WNT9a</i> as a potential gene associated with improved efficacy and <i>ATF3</i> with enhanced safety, providing valuable insights for optimizing therapeutic strategies in PDAC.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100892","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":"Advancement of Photobiomodulation Therapy Using 680 and 850 nm Light-Emitting Diodes for the Differentiation of Human Brain Endothelial Cells","authors":"Hossein Chamkouri, Lei Chen","doi":"10.1002/adtp.202500164","DOIUrl":"10.1002/adtp.202500164","url":null,"abstract":"<p>Photobiomodulation (PBM) has emerged as a promising therapeutic approach for modulating cellular behavior and improving health outcomes, particularly in the context of vascular health. Despite growing interest in PBM, a key gap exists in understanding how specific wavelengths, such as 680 and 850 nm, affect endothelial cell function. While light's general effects on cell viability and mitochondrial function are known, the precise mechanisms underlying PBM's influence on endothelial cells remain unclear, limiting the optimization of PBM protocols for vascular dysfunction. In this study, the effects of PBM on endothelial cells are investigated using the light peaked at 680 and 850 nm with full width at half maximum (FWHM) about 17.5 and 25.1 nm, respectively, assessing cell viability, mitochondrial activity, reactive oxygen species (ROS) production, calcium flux (Ca<sup>2+</sup>), and transepithelial electrical resistance (TEER). These findings demonstrate that PBM exposure enhances mitochondrial function, reduces oxidative stress, and modulates calcium signaling, all of which contribute to changes in endothelial barrier integrity. These results highlight the potential of PBM as a novel therapeutic strategy for enhancing endothelial cell function and addressing endothelial dysfunction, opening new avenues for future research and clinical applications in vascular health.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100893","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}
Murat Kavruk, Dide Su Demirel, Farzaneh Bonyadi, Buket Çakmak Güner, Ali Doğan Dursun, Cekdar Vakifahmetoglu, Bilge Güvenç Tuna, Uğur Şahin, Veli Cengiz Ozalp
{"title":"Enhanced Doxorubicin Cytotoxicity on Breast Cancer Spheroids by Aptamer Targeted Co-Delivery with Hyaluronidase","authors":"Murat Kavruk, Dide Su Demirel, Farzaneh Bonyadi, Buket Çakmak Güner, Ali Doğan Dursun, Cekdar Vakifahmetoglu, Bilge Güvenç Tuna, Uğur Şahin, Veli Cengiz Ozalp","doi":"10.1002/adtp.202500134","DOIUrl":"https://doi.org/10.1002/adtp.202500134","url":null,"abstract":"<p>Breast cancer is one of the most prevalent solid tumors in women and can be classified into subtypes based on molecular characteristics, such as hormone receptor status and HER2 expression. Aptamers, highly specific affinity molecules, are extensively studied for targeted drug delivery using nanocarriers to enhance anti-cancer efficacy. This study focused on HER2-responsive co-delivery of doxorubicin and hyaluronidase via aptamer-gated mesoporous silica nanoparticles to improve therapeutic outcomes in solid tumors. SK-BR-3 spheroids are employed as a model for resistant tumor environments in solid tumors. Previous research is shown that conjugating cytotoxic drugs with nanoparticles or cells enhances drug penetration into tumor spheroids. In this work, doxorubicin is loaded into mesoporous silica nanoparticles and capped with HER2-specific aptamers, while the particle surface is functionalized with hyaluronidase. This dual-functionalized nanocarrier system achieves an ≈8.5-fold increase in cytotoxicity compared to aptamer-targeted delivery lacking hyaluronidase. The enhanced effect is attributed to hyaluronidase-mediated loosening of the spheroid structure, facilitating nanoparticle penetration and localized release of doxorubicin at high concentrations on HER2-positive cells.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284588","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}