Jaehun Lee , Youngwon Kim , Hyo-Il Jung , Jiseok Lim , Bong Seop Kwak
{"title":"Channel-assembling tumor microenvironment on-chip for evaluating anticancer drug efficacy","authors":"Jaehun Lee , Youngwon Kim , Hyo-Il Jung , Jiseok Lim , Bong Seop Kwak","doi":"10.1016/j.jconrel.2024.11.030","DOIUrl":"10.1016/j.jconrel.2024.11.030","url":null,"abstract":"<div><div>Organ-on-a-chip is an advanced system for evaluating drug response in diseases. It simulates the <em>in vivo</em> tumor microenvironment, aiding in the understanding of drug mechanisms and tumor responses. It mimics the structure of the tumor microenvironment and the dynamic conditions within the body. As a result, it holds the potential for applications in precision and personalized medicine. However, there are still limitations in sequential development processes and complex structures, resulting in time-consuming molecular interference during system development. In this study, we developed a channel-assembling tumor microenvironment-on-chip (CATOC) system to overcome these limitations. CATOC was easily segmented into blood vessels and a tumor microenvironment-on-chip, which can be independently developed. The tumor microenvironment-on-chip consists of two independent channels for evaluating drug responses in different types of tumor microenvironments. Each fully developed system was physically interconnected to create a CATOC. Interconnected CATOC was used to validate chemical and targeted anticancer drug responses in different subtypes of the breast tumor microenvironment. We also emphasized the significance of on-chip experiments by observing the drug response of tumor spheroids on CATOC and scaffold-free platforms.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 376-384"},"PeriodicalIF":10.5,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced secretion of growth factors from ADSCs using an enzymatic antioxidant hydrogel in inflammatory environments and its therapeutic effect","authors":"Kiyoon Min, Myeongseok Jung, Giyoong Tae","doi":"10.1016/j.jconrel.2024.11.041","DOIUrl":"10.1016/j.jconrel.2024.11.041","url":null,"abstract":"<div><div>A catalytic ROS-scavenging hydrogel (HGel) was developed to enhance the growth factor secretion and the therapeutic efficacy of human adipose-derived stem cells (hADSCs) in inflammatory environments. The HGel is composed of heparin and hyaluronic acid, further functionalized with hemin to endow superoxide dismutase and catalase activities. The functionalization of hemin enables the HGel to effectively scavenge ROS (superoxide and H<sub>2</sub>O<sub>2</sub>), thereby protecting encapsulated hADSCs from oxidative stress and maintaining their metabolic activities. As a result, the HGel enhanced growth factor secretion of hADSCs in inflammatory conditions compared to non-functionalized, bare heparin/hyaluronic acid hydrogel (Gel). The therapeutic efficacy of the hADSC-encapsulated HGel (C/HGel) was evaluated in a diabetic wound model. The C/HGel significantly accelerated wound closure, reduced ROS levels, mitigated inflammation, and promoted angiogenesis compared to the hADSC-encapsulated Gel (C/Gel) as well as the HGel itself. The HGel has the potential to be utilized as an excellent cell carrier for stem cell therapy in various inflammatory diseases. Overall, this study demonstrated a strategy of enhancing growth factor secretion from stem cells using catalytic antioxidant hydrogels for superior regenerative effects in cell therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 301-314"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haixin Tan , Ziwei Hu , Jiajun Miao , Bin Chen , Huaan Li , Junbin Gao , Yicheng Ye , Wenxin Xu , Jiamiao Jiang , Hanfeng Qin , Hao Tian , Fei Peng , Yingfeng Tu
{"title":"Enzymatic nanomotors with chemotaxis for product-based cancer therapy","authors":"Haixin Tan , Ziwei Hu , Jiajun Miao , Bin Chen , Huaan Li , Junbin Gao , Yicheng Ye , Wenxin Xu , Jiamiao Jiang , Hanfeng Qin , Hao Tian , Fei Peng , Yingfeng Tu","doi":"10.1016/j.jconrel.2024.11.042","DOIUrl":"10.1016/j.jconrel.2024.11.042","url":null,"abstract":"<div><div>The development of an intelligent nanomotor system holds great promise for enhancing the efficiency and effectiveness of antitumor therapy. Leveraging the overexpressed substances in the tumor microenvironment as propellants and chemotactic factors for enzyme-powered nanomotors represents a versatile and compelling approach. Herein, a plasma amine oxidase (PAO)-based chemotactic nanomotor system has been successfully developed, with the ability to enzymatically produce toxic acrolein and H<sub>2</sub>O<sub>2</sub> from the upregulated polyamines (PAs) in the tumor microenvironment for active tumor therapy. Zwitterionic polymeric nanoparticles with superior biocompatibility are synthesized, followed by PAO modification <em>via</em> electrostatic interactions. As expected, the resulting nanomotor system exhibits positive chemotaxis toward PAs concentration gradient. Upon reaching the tumor region, our nanomotors, actuated by the tumor microenvironmental PAs, effectively enhance diffusion and enable deep penetration into the tumor site. This leads to the induction of tumor apoptosis and simultaneous inhibition of tumor invasion and migration by decomposing PAs into toxic products. By smartly utilizing the consumption of these local chemotactic factors and their enzymatic products, our nanomotor system provides a versatile and intelligent platform for active and enhanced tumor therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 288-300"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiming Qin , Feiyun Cui , Yifei Lu , Peng Yang , Weiming Gou , Zixuan Tang , Shan Lu , H. Susan Zhou , Gaoxing Luo , Xiaoyan Lyu , Qing Zhang
{"title":"Toward precision medicine: End-to-end design and construction of integrated microneedle-based theranostic systems","authors":"Yiming Qin , Feiyun Cui , Yifei Lu , Peng Yang , Weiming Gou , Zixuan Tang , Shan Lu , H. Susan Zhou , Gaoxing Luo , Xiaoyan Lyu , Qing Zhang","doi":"10.1016/j.jconrel.2024.11.020","DOIUrl":"10.1016/j.jconrel.2024.11.020","url":null,"abstract":"<div><div>With the growing demand for precision medicine and advancements in microneedle technology, microneedle-based drug delivery systems have evolved into integrated theranostic platforms. However, the development of these systems is currently limited by the absence of clear conclusions and standardized construction strategies. The end-to-end concept offers an innovative approach to theranostic systems by creating a seamless process that integrates target sampling, sensing, analysis, and on-demand drug delivery. This approach optimizes each step based on data from the others, effectively eliminating the traditional separation between drug delivery and disease monitoring. Furthermore, by incorporating artificial intelligence and machine learning, these systems can enhance reliability and efficiency in disease management, paving the way for more personalized and effective healthcare solutions. Based on the concept of end-to-end and recent advancements in theranostic systems, nanomaterials, electronic components, micro-composites, and data science, we propose a modular strategy for constructing integrated microneedle-based theranostic systems by detailing the methods and functions of each critical component, including monitoring, decision-making, and on-demand drug delivery units, though the total number of units might vary depending on the specific application. Notably, decision-making units are emerging trends for fully automatic and seamless systems and featured for integrated microneedle-based theranostic systems, which serve as a bridge of real-time monitoring, on-demand drug delivery, advanced electronic engineering, and data science for personalized disease management and remote medical application. Additionally, we discuss the challenges and prospects of integrated microneedle-based theranostic systems for precision medicine and clinical application.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 354-375"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Da In Jeong , Qiaojun Hao , Song Yi Lee , Sungyun Kim , Mrinmoy Karmakar , Seongnam Chu , Miso Park , Hyun-Jong Cho
{"title":"Cellulose nanocrystal-annealed hydrogel system for local chemo-metabolic therapy of melanoma","authors":"Da In Jeong , Qiaojun Hao , Song Yi Lee , Sungyun Kim , Mrinmoy Karmakar , Seongnam Chu , Miso Park , Hyun-Jong Cho","doi":"10.1016/j.jconrel.2024.11.015","DOIUrl":"10.1016/j.jconrel.2024.11.015","url":null,"abstract":"<div><div>A cellulose nanocrystal (CNC)-annealed hydrogel (CAH) structure, including doxorubicin (DOX) and 2-deoxy-<span>d</span>-glucose (2DG), was developed for local chemo-metabolic therapy (LCMT) of melanoma. DOX has been used as a chemotherapeutic agent because of its intercalation into DNA and generation of free radicals. 2DG has been used as a glycolytic inhibitor in multiple metabolic therapies in combination with DOX. Covalent and non-covalent (<em>i.e.,</em> ionic and hydrogen bonding) binding approaches between CNC and drug cargo (<em>i.e.,</em> DOX and 2DG) were used to tune the rheological properties of the CAH structure to achieve sustained drug release. Reduction of reduced nicotinamide adenine dinucleotide phosphate, adenosine triphosphate, and mitochondrial membrane potential, and elevation of cellular reactive oxygen species and cleaved caspases 3 and 7 were observed following treatment with CNC/DOX/2DG in B16F10 cells. Glutathione depletion, enhanced lipid peroxidation, and decreased lactate levels were observed in the CNC/DOX/2DG group. After intratumoral injection of the CNC/DOX/2DG hydrogel into B16F10 tumor-bearing mice, stronger tumor growth suppression and anti-recurrence capabilities were observed. These findings imply that the viscoelastically modulated CAH system can be a strong candidate for LCMT of melanoma.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 324-338"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biocompatible DNA hydrogel composed of minimized Takumi-shaped DNA nanostructure exhibits sustained retention after in vivo administration.","authors":"Jian Jin, Kosuke Kusamori, Takumi Tanifuji, Yoshifumi Yamagata, Shoko Itakura, Makiya Nishikawa","doi":"10.1016/j.jconrel.2024.11.052","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.052","url":null,"abstract":"<p><p>Our previous studies showed that DNA hydrogels containing unmethylated CpG motifs effectively induced antigen-specific immune responses when combined with the appropriate antigens. A potential drawback of existing DNA hydrogels for further applications is the need for many oligodeoxynucleotide (ODN) types. Therefore, in this study, we attempted to optimize and minimize the nanostructured DNA units for DNA hydrogels to reduce the preparation cost, design difficulty, and possible risk of sequence-dependent off-target effects, and prepare DNA hydrogels with sustained retention ability. A Takumi-shaped unit with a stem and four flanking cohesive parts was constructed using one type of ODN with a palindromic sequence. A DNA hydrogel was prepared by mixing two Takumi-shaped units with complementary cohesive parts. The required length of the cohesive part was first examined using ODNs with 14 or 18 bases of stem length. Electrophoresis, melting temperature measurements, and viscoelastic analysis showed that the properties of the cohesive part determined the hydrogel properties. ODNs with a cohesive part consisting of GC-rich 5'-ccgcaagacg-3' efficiently formed a hydrogel with sustained retention in mice after administration. Several ODNs with optimized cohesive sequences and different stem lengths and sequences were designed. Analyses showed that a stem of 10 bases or longer was required for efficient hydrogel formation, and ODNs with a 12-base stem part exhibited the most prolonged retention after subcutaneous injection into mice. Thus, the present study demonstrated the requirements of minimal DNA units for preparing DNA hydrogels with sustained retention ability.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mayuka Nakajima , Neha Kapate , John R. Clegg , Mayumi Ikeda-Imafuku , Kyung Soo Park , Ninad Kumbhojkar , Vinny Chandran Suja , Supriya Prakash , Lily Li-Wen Wang , Koichi Tabeta , Samir Mitragotri
{"title":"Backpack-carrying macrophage immunotherapy for periodontitis","authors":"Mayuka Nakajima , Neha Kapate , John R. Clegg , Mayumi Ikeda-Imafuku , Kyung Soo Park , Ninad Kumbhojkar , Vinny Chandran Suja , Supriya Prakash , Lily Li-Wen Wang , Koichi Tabeta , Samir Mitragotri","doi":"10.1016/j.jconrel.2024.11.037","DOIUrl":"10.1016/j.jconrel.2024.11.037","url":null,"abstract":"<div><div>Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy. This hurdle can be overcome by cellular backpacks (BPs), discoidal particles that adhere on the macrophage surface and regulate M1/M2 phenotypic shift in an environment-independent manner. In this study, we engineered IL-4 BPs for maintaining macrophages in the M2 phenotype to regulate excess inflammation in periodontitis, a major oral infectious disease. IL-4 BPs induced and maintained M2 phenotype in macrophages <em>in vitro</em> for several days. After injection of macrophages carrying IL-4 BPs into the gingiva, the cells stayed in the tissue for over 5 days and maintained the M2 phenotype in the disease sites. Furthermore, treatment with IL-4 BP-macrophages significantly suppressed the disease progression. Altogether, a treatment with BP-carrying macrophages offers a promising local therapy against periodontitis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 315-323"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thi-Nhan Phan , Ching-Hsiang Fan , Hsien-Chu Wang , Hao-Li Liu , Yu-Chun Lin , Chih-Kuang Yeh
{"title":"Modulation of GABAergic neurons in acute epilepsy using sonogenetics","authors":"Thi-Nhan Phan , Ching-Hsiang Fan , Hsien-Chu Wang , Hao-Li Liu , Yu-Chun Lin , Chih-Kuang Yeh","doi":"10.1016/j.jconrel.2024.11.029","DOIUrl":"10.1016/j.jconrel.2024.11.029","url":null,"abstract":"<div><div>Epilepsy, a neurological disorder caused by hypersynchronous neural disturbances, has traditionally been treated with surgery, pharmacotherapy, and neuromodulation techniques such as deep brain stimulation and vagus nerve stimulation. However, these methods are often limited by invasiveness, off-target effects, and poor resolution. We present a noninvasive alternative utilizing sonogenetics to selectively stimulate γ-aminobutyric acid (GABA)ergic neurons in the amygdala through engineered auditory-sensing protein, mPrestin (N7T, N308S), in a pentylenetetrazole-induced rat model. Activation of GABAergic neurons induced by the sonication with 0.5-MHz transcranial ultrasound can modulate epileptiform activity by 50 %. Electrophysiological recordings confirmed effective neuromodulation and persistent seizure suppression up to 60 min post-treatment without tissue damage, inflammation, or apoptosis. This sonogenetic approach offers a promising, safe method for epilepsy management by targeting GABAergic neurons.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 341-353"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanming Xia , Bo Shi , Keke Wang , Lixin Hu , Qiran Wang , Shuxian Xu , Xiaohu Wang , Pengcheng Xu , Yuanbin She , Haitang Xie , Suxin Li , Lifang Yin
{"title":"A trinity STING-activating nanoparticle harnesses cancer cell STING machinery for enhanced immunotherapy","authors":"Yanming Xia , Bo Shi , Keke Wang , Lixin Hu , Qiran Wang , Shuxian Xu , Xiaohu Wang , Pengcheng Xu , Yuanbin She , Haitang Xie , Suxin Li , Lifang Yin","doi":"10.1016/j.jconrel.2024.11.035","DOIUrl":"10.1016/j.jconrel.2024.11.035","url":null,"abstract":"<div><div>The cGAS-STING axis is a promising therapeutic target against cancer. However, most activators require STING signaling in the host, especially within antigen-presenting cells, which are rare in a cold tumor microenvironment. The cGAS-STING cascade is also present within cancer cells but with suppressed activity. Such a paradoxical situation may account for the clinical failures. Herein, we develop a trinity STING-activating nanoparticle (CMTP) coordinated with cGAMP, Mn<sup>3+</sup>, and porphyrin to awaken autologous STING signaling in cancer cells. CMTP disintegrates into Mn<sup>2+</sup> and TCPP upon elevated glutathione in cancer cells, where TCPP triggers mitochondrial DNA leakage, enhancing cGAS enzymatic activity in coordination with Mn<sup>2+</sup>, while concurrent cGAMP release from framework synergizes to amply STING activity. Consequently, CMTP exploits cancer cells as reservoirs for cGAS-STING signaling to promote DC maturation and T cell priming. A single administration of CMTP demonstrates robust efficacy in both hot MC38 and cold 4 T1 murine tumors. Genetic knockout studies confirm that STING in cancer cells, rather than in the host, is critical for antitumor performance. The feasibility of immune modulation is further validated in resected human patient tissues. This work presents a potent STING-activating nanomedicine based on coordination chemistry and underscores the potential of harnessing cancer cells' autologous cGAS-STING machinery in immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 256-266"},"PeriodicalIF":10.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}