Eman Serag, Esmail M El-Fakharany, Sherif F Hammad, Mohamed E El-Khouly
{"title":"Metal-organic framework MIL-101(Fe) functionalized with folic acid as a multifunctional nanocarrier for targeted chemotherapy-photodynamic therapy.","authors":"Eman Serag, Esmail M El-Fakharany, Sherif F Hammad, Mohamed E El-Khouly","doi":"10.1039/d4bm01738b","DOIUrl":"https://doi.org/10.1039/d4bm01738b","url":null,"abstract":"<p><p>A novel folic acid-conjugated, iron-based MOF (MIL-101(Fe)) loaded with 1,8-acridinediones (DO8) was developed for targeted photodynamic therapy (PDT) of HepG-2 cells. This composite aims to trigger an anticancer response through sequential PDT and chemotherapy. The nanocomposite exhibited high stability in a physiological environment with a pH of 7.4. It was also able to release DO8 continuously in an acidic environment with a pH of 5, which shows that it can adapt to the conditions in the tumor microenvironment. The MIL-101(Fe)MOF-FA@DO8 nanoparticles (NPs) with 30% and 50% DO8 have been studied <i>in vitro</i> under different conditions (light and dark) and have been shown to be compatible with living tissues and specifically target HepG-2 cells. The IC<sub>50</sub> values of 50% DO8 and 30% DO8 loaded MOF-FA were found to be 88.67 and 105.9 μg mL<sup>-1</sup> under dark conditions, respectively. Under light conditions, they demonstrated the highest efficacy in inhibiting tumor cell growth. The IC<sub>50</sub> values were found to be 8.94 and 11.78 μg mL<sup>-1</sup>. Flow cytometry analysis of annexin V/PI-stained apoptotic and necrotic cells in HepG-2 cells treated with the modified MIL-101-FA@50% DO8 NPs at IC<sub>50</sub> doses under both dark and light conditions indicates that the primary mechanism of cell death is necrosis, likely due to the enhanced formation of reactive oxygen species (ROS) under light conditions compared to that under dark conditions. This increased reactive oxygen species (ROS) generation leads to extensive membrane rupture, resulting in significant cell damage after treatment with the modified MIL-101-FA@50% DO8 NPs. These findings underscore the potential of this nanocomposite as an effective PDT agent for targeted cancer therapy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Self-targeted nanosystem for enhanced chemodynamic cancer therapy.","authors":"Kanwal Asif, Md Mahbubur Rahman, Vincenzo Canzonieri, Isabella Caligiuri, Flavio Rizzolio, Muhammad Adeel","doi":"10.1039/d4bm01683a","DOIUrl":"https://doi.org/10.1039/d4bm01683a","url":null,"abstract":"<p><p>Chemodynamic therapy (CDT) could have a significant potential for advancing cancer treatment <i>via</i> the utilization of Fenton and Fenton-like reactions, which produce toxic reactive species. Nonetheless, the efficacy of CDT is constrained by the limited availability of catalyst ions capable of decomposing pre-existing intracellular H<sub>2</sub>O<sub>2</sub> and generating reactive oxygen species (ROS) necessary to achieve a therapeutic response. To address these limitations, a tailored strategy has been developed to enhance the efficacy of Fenton-like reactions to eradicate selectively cancer cells. This innovative approach involves the utilization of dual metal cations (Zn<sup>2+</sup>, Fe<sup>2+</sup>) within zinc nitroprusside (ZnNP) material. Remarkably, this method takes advantage of the acidic conditions prevalent in tumors, thus eliminating the need for external stimuli. Through these advancements, the tailored approach exhibits the potential to specifically target and eliminate cancer cells, overcoming the mentioned limitations. A simple mixing technique was utilized to synthesize ZnNP, which was structurally and morphologically characterized. Furthermore, extensive <i>in vitro</i> investigations were conducted to assess its anti-tumoral mechanism of action. ZnNP exhibits a remarkable capability to increase intracellular H<sub>2</sub>O<sub>2</sub> within cells. This process leads to the generation of various reactive species, including hydroxyl (˙OH) and superoxide (O<sub>2</sub>˙<sup>-</sup>) radicals, and peroxynitrite (ONOO<sup>-</sup>), which act as apoptotic inducers specifically targeting cancer cells. Cellular uptake studies have shown that ZnNP enters the lysosomes, evades degradation, and takes advantage of their acidic pH environment to significantly increase the production of ROS. These findings are further supported by the activation of multiple oxidative genes. Furthermore, the biocompatibility of ZnNP has been demonstrated in <i>ex vivo</i> models using healthy liver cells. Notably, ZnNP exhibited therapeutic effectiveness in high-grade serous ovarian cancer (HGSOC) patient-derived tumor organoids (PDTO), further confirming its potential as a therapeutic agent. The present study highlights the therapeutic potential of ZnNP as a generator of multiple ROS <i>via</i> a Fenton-like reaction. This research offers a promising therapeutic approach for CDT application in combatting HGSOC, a highly aggressive and life-threatening cancer.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aoxiang Jin, Chunxiang Lu, Chuang Gao, Hao Qiao, Yi Zhang, Huazhen Liu, Wenbin Sun, Qiqi Dai, Yuanyuan Liu
{"title":"Biomimetic basement membranes: advances in materials, preparation techniques, and applications in <i>in vitro</i> biological models.","authors":"Aoxiang Jin, Chunxiang Lu, Chuang Gao, Hao Qiao, Yi Zhang, Huazhen Liu, Wenbin Sun, Qiqi Dai, Yuanyuan Liu","doi":"10.1039/d4bm01682c","DOIUrl":"https://doi.org/10.1039/d4bm01682c","url":null,"abstract":"<p><p><i>In vitro</i> biological model technology has become a cornerstone of modern biological research, driving advancements in drug screening, physiological and pathological studies, and tissue implantation applications. The natural basement membrane (BM), a homogeneous structure, provides critical physical and biological support for tissues and organs. To replicate its function, researchers have developed biomimetic BMs using advanced fabrication technologies, which are increasingly applied to <i>in vitro</i> models. This review explores the materials, preparation techniques, and applications of biomimetic BMs across various biological models, highlighting their advantages and limitations. Additionally, it discusses recent progress in the field and identifies current challenges in achieving BM simulations that closely mimic native structures. Future directions and recommendations are provided to guide the development of high-performance biomimetic BM materials and their manufacturing processes.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margot J. Amitrano, Mina Cho, Eva M. Coughlin, Sean P. Palecek and William L. Murphy
{"title":"Synthetic hydrogels support robust and reproducible cardiomyocyte differentiation†","authors":"Margot J. Amitrano, Mina Cho, Eva M. Coughlin, Sean P. Palecek and William L. Murphy","doi":"10.1039/D4BM01636J","DOIUrl":"10.1039/D4BM01636J","url":null,"abstract":"<p >Cardiomyocyte manufacturing from human pluripotent stem cells is limited by the variability of differentiation efficiencies, partly attributed to the widespread use of the tumor-derived substrate Matrigel. Here, we describe a screening approach to identify fully-defined synthetic PEG hydrogels that support iPSC-derived cardiac progenitor cell (iPSC-CPC) adhesion, survival, and differentiation into iPSC-derived cardiomyocytes (iPSC-CMs). Our PEG hydrogels supported superior iPSC-CM differentiation efficiency, with a 24% increase in cTnT expression, and greater reproducibility when compared to cells cultured on Matrigel. By combining our 5-level, 3-variable full factorial screening approach with multi-variate analysis, we showed that all substrate variables manipulated here (adhesion ligand type/concentration, stiffness) had a significant influence on iPSC-CPC confluency and that iPSC-CM differentiation was significantly influenced by adhesion ligands. These results highlight the benefit of synthetic, tunable cell culture substrates and multi-variate screening studies to identify substrate formulations for a targeted cell behavior.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 8","pages":" 2142-2151"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antitumor immune response elicited by M2 TAM-specific DDS <i>via</i> C-type lectin CD209b using cholesteryl pullulan nanogel as a protein drug carrier.","authors":"Takaaki Nakatsukasa, Daisuke Muraoka, Situo Deng, Kiyoshi Yasui, Shin-Ichi Sawada, Asako Shimoda, Hirokazu Matsushita, Keitaro Matsumoto, Takeshi Nagayasu, Naozumi Harada, Kazunari Akiyoshi, Hiroaki Ikeda","doi":"10.1039/d5bm00342c","DOIUrl":"https://doi.org/10.1039/d5bm00342c","url":null,"abstract":"<p><p>Many cancer patients develop resistance to immunotherapy, highlighting the urgent need for novel therapeutic strategies. Various factors contribute to tumor resistance to immunotherapy, among which tumor-associated macrophages (TAMs) are critical regulators of tumor sensitivity. Therefore, combining cancer immunotherapies with drug delivery systems (DDSs) targeting TAMs has become an intriguing treatment strategy. However, the target molecules used in DDSs are limited to a few receptors expressed on TAMs. Therefore, the identification of novel target molecules for TAM-specific DDS is urgently needed. The current study evaluated the ability of a cholesteryl pullulan (CHP) nanogel to target TAMs <i>via</i> mDC-SIGN (CD209b). This nanogel encapsulated the cytotoxic protein drug Pseudomonas exotoxin A and was injected into a tumor-bearing mouse model. This treatment significantly reduced the abundance of CD209b-positive M2 TAMs and enhanced antitumor immune responses. Ultimately, tumor growth was suppressed, even in a low-immunogenic tumor model. Hence, CD209b is an effective target molecule for M2 TAM-specific DDSs that can be used to develop novel cancer therapies.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tamara Rossy, Laura Schwendeman, Sonika Kohli, Maheera Bawa, Pavankumar Umashankar, Roi Habba, Oren Tchaicheeyan, Ayelet Lesman, Ritu Raman
{"title":"Leveraging microtopography to pattern multi-oriented muscle actuators.","authors":"Tamara Rossy, Laura Schwendeman, Sonika Kohli, Maheera Bawa, Pavankumar Umashankar, Roi Habba, Oren Tchaicheeyan, Ayelet Lesman, Ritu Raman","doi":"10.1039/d4bm01017e","DOIUrl":"10.1039/d4bm01017e","url":null,"abstract":"<p><p>Engineering skeletal muscle tissue with precisely defined alignment is of significant importance for applications ranging from drug screening to biohybrid robotics. Aligning 2D contractile muscle monolayers, which are compatible with high-content imaging and can be deployed in planar soft robots, typically requires micropatterned cues. However, current protocols for integrating microscale topographical features in extracellular matrix hydrogels require expensive microfabrication equipment and multi-step procedures involving error-prone manual handling steps. To address this challenge, we present STAMP (simple templating of actuators <i>via</i> micro-topographical patterning), an easily accessible and cost-effective one-step method to pattern microtopography of various sizes and configurations on the surface of hydrogels using reusable 3D printed stamps. We demonstrate that STAMP enables precisely controlling the alignment of mouse and human skeletal muscle fibers without negatively impacting their maturation or function. To showcase the versatility of our technique, we designed a planar soft robot inspired by the iris, which leverages spatially segregated regions of concentric and radial muscle fibers to control pupil dilation. Optogenetic skeletal muscle fibers grown on a STAMPed iris substrates formed a multi-oriented actuator, and selective light stimulation of the radial and concentric fibers was used to control the function of the iris, including pupil constriction. Computational modeling of the biohybrid robot as an active bilayer matched experimental outcomes, showcasing the robustness of our STAMP method for designing, fabricating, and testing planar biohybrid robots capable of complex multi-DOF motion.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anika D. Kulkarni, Tasneem Mukarrama, Brendan R. Barlow and Jinhwan Kim
{"title":"Recent advances in non-invasive in vivo tracking of cell-based cancer immunotherapies","authors":"Anika D. Kulkarni, Tasneem Mukarrama, Brendan R. Barlow and Jinhwan Kim","doi":"10.1039/D4BM01677G","DOIUrl":"10.1039/D4BM01677G","url":null,"abstract":"<p >Immunotherapy has been at the forefront of cancer treatment research in recent years due to an increased understanding of the immune system's role in cancer and the substantial benefits it has demonstrated compared to conventional treatment methods. In particular, immune cell-based approaches utilizing T cells, natural killer (NK) cells, macrophages, and more have shown great potential as cancer treatments. While these treatments hold promise, there are still numerous issues that limit their clinical translation, including a lack of understanding of their mechanisms and inconsistent responses to treatment. Traditionally, tissue or blood samples are collected as a means of monitoring treatment progression. However, these <em>in vitro</em> diagnostics are invasive and provide limited information about the real-time status of the treatment or its long-term effectiveness. To address these limitations, novel non-invasive imaging modalities have been developed. These include optical imaging, X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT), and photoacoustic (PA) imaging. This review focuses on methods for tracking cell-based cancer immunotherapies using these <em>in vivo</em> imaging modalities, thereby enhancing real-time monitoring of their therapeutic effect and predictions of their long-term efficacy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 8","pages":" 1939-1959"},"PeriodicalIF":5.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunxiang Lu, Aoxiang Jin, Huazhen Liu, Chuang Gao, Wenbin Sun, Yi Zhang, Qiqi Dai and Yuanyuan Liu
{"title":"Advancing tissue engineering through vascularized cell spheroids: building blocks of the future","authors":"Chunxiang Lu, Aoxiang Jin, Huazhen Liu, Chuang Gao, Wenbin Sun, Yi Zhang, Qiqi Dai and Yuanyuan Liu","doi":"10.1039/D4BM01206B","DOIUrl":"10.1039/D4BM01206B","url":null,"abstract":"<p >Vascularization is a crucial aspect of biofabrication, as the development of vascular networks is essential for tissue survival and the optimization of cellular functions. Spheroids have emerged as versatile units for vascularization, demonstrating significant potential in angiogenesis and prevascularization for tissue engineering and regenerative medicine. However, a major challenge in creating customized vascularized spheroids is the construction of a biomimetic extracellular matrix (ECM) microenvironment. This process requires careful regulation of environmental factors, including the modulation of growth factors, the selection of culture media, and the co-culture of diverse cell types. Recent advancements in biofabrication have expanded the potential applications of vascularized spheroids. The integration of microfluidic technology with bioprinting offers promising solutions to existing challenges in regenerative medicine. Spheroids have been widely studied for their ability to promote vascularization in <em>in vitro</em> models. This review highlights the latest developments in vascularized biofabrication, and systematically explores strategies for constructing vascularized spheroids. We provide a comprehensive analysis of spheroid applications in specific tissues, including skin, liver, bone, cardiac, and tumor models. Finally, the review addresses the major challenges and future directions in the field.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 8","pages":" 1901-1922"},"PeriodicalIF":5.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingna Wang, Zehua Chen, Zhaohui Dai, Meng Li, Bo Chen and Bing Wang
{"title":"Membrane-intercalating conjugated oligoelectrolytes for lipid membrane imaging","authors":"Lingna Wang, Zehua Chen, Zhaohui Dai, Meng Li, Bo Chen and Bing Wang","doi":"10.1039/D5BM00028A","DOIUrl":"10.1039/D5BM00028A","url":null,"abstract":"<p >Membrane-intercalating conjugated oligoelectrolytes (MICOEs), a class of phospholipid bilayer mimics, demonstrate an exceptional ability to spontaneously integrate into biological membranes through a combination of electrostatic and hydrophobic interactions. This unique property makes them promising candidates for membrane imaging applications. Over the past decade, MICOEs have been successfully applied to imaging and tracking a wide range of biological membranes, including microbial membranes, mammalian plasma membranes, intracellular membranes, extracellular vesicles, and artificial liposomes. Recent advancements have shed light on the imaging mechanisms of MICOEs and highlighted their potential as fluorescent probes, with a focus on structural optimization to enhance their performance. Building on these developments, this review will explore the intercalation mechanisms of MICOEs, analyze the structure–activity relationships governing their molecular design and imaging capabilities, and discuss the future challenges and emerging opportunities for their application as advanced membrane dyes.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 8","pages":" 1923-1938"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biofunctionalized nanomaterials for Parkinson's disease theranostics: potential for efficient PD biomarker detection and effective therapy.","authors":"Saheli Sabnam, Raj Kumar, Pranav","doi":"10.1039/d5bm00179j","DOIUrl":"https://doi.org/10.1039/d5bm00179j","url":null,"abstract":"<p><p>α-Synuclein (α-Syn) is a primary pathological indicator for Parkinson's disease (PD). The α-Syn oligomer is even more toxic and is responsible for PD. Hence, identifying α-Syn and its oligomers is an interesting approach to diagnosing PD. The prevention strategies for oligomer formation could be therapeutic in treating PD. Various conventional strategies have been developed for the management of PD. However, their clinical applications are limited due to toxicity, off-targeting, side effects, and poor bioavailability. Recently, nanomaterials have gained significant attention due to unique physicochemical characteristics such as nanoscale size, large surface area, flexibility of functionalization, and ability to protect and control a loaded payload. Functionalizing the surface of nanoparticles with a desired targeting agent could offer targeted delivery of the payload at the site of action due to specificity and selectivity against complementary molecules. Among various functionalization approaches, biomolecule-functionalized nanomaterials offer benefits such as enhanced bioavailability, improved internalization into target cells through receptor-mediated endocytosis, and delivery of therapeutics across the BBB (blood-brain barrier). In this review, we initially discussed the major milestones related to PD and highlighted the therapeutic strategies focused on clinical trials. The strategies of biomolecule functionalization of nanomaterials and their application in detecting and preventing α-Syn oligomer for the diagnosis and therapy of PD, respectively, have been reviewed comprehensively. Ultimately, we have outlined the conclusions, highlighted the limitations and challenges, and provided insight into future perspectives and alternative approaches that must be investigated.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}