Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-02-17DOI: 10.1080/10717544.2025.2463427
Arwa Kurabi, Emily Sereno, Allen F Ryan
{"title":"Peptides rapidly transport antibiotic across the intact tympanic membrane to treat a middle ear infection.","authors":"Arwa Kurabi, Emily Sereno, Allen F Ryan","doi":"10.1080/10717544.2025.2463427","DOIUrl":"10.1080/10717544.2025.2463427","url":null,"abstract":"<p><p>The tympanic membrane (TM) forms an impenetrable barrier to medical therapies for middle ear (ME) diseases like otitis media. By screening a phage-displayed peptide library, we have previously discovered rare peptides that mediate the active transport of cargo across the intact membrane of animals and humans. Since the M13 filamentous bacteriophage on which the peptides are expressed are large (nearly 1 µm in length), this offers the possibility of noninvasively delivering drugs, large drug packages, or gene therapy to the ME. To evaluate this possibility, EDC chemistry was employed to covalently attach amoxicillin, or neomycin molecules to phage bearing a trans-TM peptide, as a model for large drug packages. Eight hours after application of antibiotic-phage to the TM of infected rats, ME bacterial titers were substantially reduced compared to untreated animals. As a control, antibiotic was linked to wild-type phage, not bearing any peptide, and application to the TM did not affect ME bacteria. The results support the ability of rare peptides to actively deliver pharmacologically relevant amounts of drugs through the intact TM and into the ME. Moreover, since bacteriophage engineered to express peptides are viral vectors, the trans-TM peptides could also transport other viral vectors into the ME.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2463427"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-04-11DOI: 10.1080/10717544.2025.2484277
Miriam Ana González-Cela-Casamayor, María J Rodrigo, Marco Brugnera, Inés Munuera, Teresa Martínez-Rincón, Catalina Prats-Lluís, Pilar Villacampa, Julián García-Feijoo, Luis E Pablo, Irene Bravo-Osuna, Elena Garcia-Martin, Rocío Herrero-Vanrell
{"title":"Ketorolac, melatonin and latanoprost tri-loaded PLGA microspheres for neuroprotection in glaucoma.","authors":"Miriam Ana González-Cela-Casamayor, María J Rodrigo, Marco Brugnera, Inés Munuera, Teresa Martínez-Rincón, Catalina Prats-Lluís, Pilar Villacampa, Julián García-Feijoo, Luis E Pablo, Irene Bravo-Osuna, Elena Garcia-Martin, Rocío Herrero-Vanrell","doi":"10.1080/10717544.2025.2484277","DOIUrl":"https://doi.org/10.1080/10717544.2025.2484277","url":null,"abstract":"<p><p>Glaucoma is a multifactorial neurodegenerative disease that affects the retina and optic nerve. The aim of this work was to reach different therapeutics targets by co-encapsulating three neuroprotective substances with hypotensive (latanoprost), antioxidant (melatonin) and anti-inflammatory (ketorolac) activity in biodegradable poly (lactic-co-glycolic acid) (PLGA) microspheres (MSs) capable of releasing the drugs for months after intravitreal injection, avoiding the need for repeated administrations. Multi-loaded PLGA MSs were prepared using the oil-in-water emulsion solvent extraction-evaporation technique and physicochemically characterized. PLGA 85:15 was the polymer ratio selected for the selected formulation. Tri-loaded MSs including vitamin E as additive showed good tolerance in retinal pigment epithelium cells after 24 h exposure (>90% cell viability). The final formulation (KMLVE) resulted in 33.58 ± 5.44 µm particle size and drug content (µg/mg MSs) of 39.70 ± 5.89, 67.28 ± 4.17 and 7.51 ± 0.58 for melatonin, ketorolac and latanoprost respectively. KMLVE were able to release in a sustained manner the three drugs over 70 days. KMLVE were injected at 2 and 12 weeks in Long-Evans rats (n = 20) after the induction of chronic glaucoma. Ophthalmological tests were performed and compared to not treated glaucomatous (n = 45) and healthy (n = 17) animals. Treated glaucomatous rats reached the lowest intraocular pressure, enhanced functionality of bipolar and retinal ganglion cells and showed greater neuroretinal thickness by optical coherence tomography (<i>p</i> < 0.05) compared to not treated glaucomatous rats at 24 weeks follow-up. According to the results, the tri-loaded microspheres can be considered as promising controlled-release system for the treatment of glaucoma.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2484277"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-08-07DOI: 10.1080/10717544.2025.2541656
Chujun Zhang, Qiaoyu Zhang, Qiao Xu, Xinyi Jiang, Yao Ma, Chaoqi Liu, Chang Zhou, Rong Liu, Yun Zhao, Yun Liu
{"title":"Ultrasound targeted microbubbles for theranostic applications in liver diseases: from molecular imaging to targeted therapy.","authors":"Chujun Zhang, Qiaoyu Zhang, Qiao Xu, Xinyi Jiang, Yao Ma, Chaoqi Liu, Chang Zhou, Rong Liu, Yun Zhao, Yun Liu","doi":"10.1080/10717544.2025.2541656","DOIUrl":"10.1080/10717544.2025.2541656","url":null,"abstract":"<p><p>Liver diseases, particularly chronic conditions leading to cirrhosis and hepatocellular carcinoma, represent a major global health burden with high mortality rates, necessitating innovative diagnostic and therapeutic approaches. Ultrasound-targeted microbubble destruction (UTMD) technology has emerged as a promising theranostic platform, combining enhanced contrast imaging with targeted drug/gene delivery capabilities. When activated by ultrasound, these microbubbles exhibit unique biophysical behaviors that significantly improve drug penetration, tissue perfusion, and site-specific delivery. This review comprehensively examines recent advancements in UTMD-based strategies for liver disease management, including microbubble design and imaging-targeted functionalization, and mechanisms of ultrasound-enhanced drug delivery, especially emerging theranostic applications. We further discuss the underlying biophysical principles governing microbubble-ultrasound interactions and their translational potential, providing insights for developing next-generation precision medicine approaches for hepatic disorders.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2541656"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-10-01DOI: 10.1080/10717544.2025.2566782
Kaikai Yu, Geng Xiao, Baichuan Chen, Na Xu, Wensen Liu
{"title":"Nucleic acid-encoded antibody gene transfer-next generation of antibody therapies.","authors":"Kaikai Yu, Geng Xiao, Baichuan Chen, Na Xu, Wensen Liu","doi":"10.1080/10717544.2025.2566782","DOIUrl":"10.1080/10717544.2025.2566782","url":null,"abstract":"<p><p>Antibody therapeutics have emerged as a cornerstone in modern biopharmaceutical development, revolutionizing treatments across diverse diseases. Recent breakthroughs in antibody discovery technologies, particularly single B-cell sorting and high-throughput sequencing, have significantly enhanced the ability to identify and isolate potent therapeutic antibodies. Despite these advances, widespread adoption of monoclonal antibody (mAb) therapies faces substantial challenges, including complex manufacturing processes, high production costs, and stringent cold-chain storage requirements. A promising solution to these limitations is nucleic acid-encoded antibody delivery, which enables in vivo production of functional antibodies. This technology delivers nucleotide sequences encoding mAbs instead of the antibody proteins themselves, effectively turning the body into a bioreactor for antibody production. By bypassing the complex purification and quality control processes associated with traditional recombinant protein production, this approach offers a more streamlined and potentially cost-effective alternative. Herein, we review current nucleic acid-based antibody delivery platforms, highlighting the unique advantages and technical challenges. We provide an in-depth analysis of the latest advancements in this field, including both viral and non-viral delivery methods, and discuss their implications for next-generation antibody therapeutics. We also examine the potential applications in infectious diseases and cancer immunotherapy, alongside regulatory and safety considerations for clinical translation. We aim to provide valuable insights and guidance for researchers and clinicians in advancing novel antibody-based therapies.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2566782"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-08-13DOI: 10.1080/10717544.2025.2544688
Tatyana Appelbaum, David A Smith, Kei Takahashi, Jennifer C Kwok, Hannah Sorenson, William A Beltran
{"title":"Impact of PEGylation and hyaluronan functionalization on lipoplex-mediated mRNA delivery to the canine retina.","authors":"Tatyana Appelbaum, David A Smith, Kei Takahashi, Jennifer C Kwok, Hannah Sorenson, William A Beltran","doi":"10.1080/10717544.2025.2544688","DOIUrl":"10.1080/10717544.2025.2544688","url":null,"abstract":"<p><p>Efficient messenger ribonucleic acid (mRNA) delivery to the retina remains challenging. This study investigated the effects of various polyethylene glycol (PEG) derivatives on the stability and uptake of cationic lipid-based mRNA lipoplexes <i>in vitro</i> and assessed the delivery of selected formulations to the canine retina. We present an optimized workflow for formulating mRNA lipoplexes in pure water, achieving high encapsulation efficiency. PEGylation enhanced stability of lipoplexes, particularly with PEG-DMG or hyaluronan conjugated to PEG-DPPE (HA-PEG-DPPE), maintaining size and zeta potential for 48 hours. RNA <i>in situ</i> hybridization (RNA-ISH) confirmed efficient internalization of PEGylated mRNA lipoplexes by cultured RAW264.7 and ARPE19 cells, though corresponding protein expression varied between cell lines. Analysis at 24 hours post-intravitreal injection of PEG-DMG- and HA-PEG-DPPE-stabilized enhanced green fluorescent protein (<i>eGFP</i>) mRNA lipoplexes revealed limited mRNA accumulation in inner retinal layers. In contrast, 24 hours after their subretinal administration, <i>eGFP</i> mRNA was detected in all retinal cell types, including photoreceptors, with accumulation comparable to endogenous rhodopsin (<i>RHO</i>) mRNA levels. eGFP protein expression, though, was limited to the retinal pigment epithelium (RPE). At 72 hours post-subretinal delivery, <i>eGFP</i> mRNA and protein persisted in the RPE. However, a marked reduction in <i>eGFP</i> levels was seen in other retinal layers, displaying a patchy pattern. Similarly, eGFP protein exhibited a patchy distribution across retinal layers outside the RPE. Furthermore, distinct differences in the cell types expressing the eGFP protein were observed between the two PEGylated mRNA lipoplex formulations. The data suggest that transfection efficiency in retinal cells is influenced by both intracellular processing of mRNA lipoplexes and their uptake, with the former playing a predominant role.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2544688"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-09-09DOI: 10.1080/10717544.2025.2557938
Chen Zhang, Luoxin Long, Hong Hu, Xinjin Zhou, Lindsey F Mao, Jing Wang, Aoran Zhang, Yuji Wang, Yi Yan, Shanhong Mao
{"title":"Integrating micro-needle jet injection and sustained GLP-1 therapy with structured feeding: a comprehensive strategy for obesity management.","authors":"Chen Zhang, Luoxin Long, Hong Hu, Xinjin Zhou, Lindsey F Mao, Jing Wang, Aoran Zhang, Yuji Wang, Yi Yan, Shanhong Mao","doi":"10.1080/10717544.2025.2557938","DOIUrl":"10.1080/10717544.2025.2557938","url":null,"abstract":"<p><p>Obesity is a global health crisis strongly linked to increased risk of type 2 diabetes, cardiovascular diseases, and other metabolic disorders. Glucagon-like peptide-1 (GLP-1) has emerged as an effective macromolecular therapeutic agent for weight management. This study addressed obesity management from three distinct perspectives: enhancing drug dispersion and bioavailability through a novel drug delivery device, extending drug half-life by developing sustained-release formulations, and sustaining the weight loss through implementation of structured dietary protocols. A new technology, micro-needle jet injection (MNJI) was developed to deliver both standard semaglutide formulations and highly viscous sustained-release formulations, achieving 100% subcutaneous delivery with predictable results. Modulation of MNJI parameters enabled the generation of various dispersion profiles, resulting in higher bioavailability compared to both needle injection (NI) and needle-free jet injection (NFJI). Sustained-release formulations, effectively administered via MNJI, exhibited higher bioavailability than the non-sustained release formulation, and positively impacted weight management efficacy in two distinct ways. First, a single injection achieved the same weight loss as five daily administrations of non-sustained release formulation. Second, a subsequent injection of the sustained-release formulations resulted in a further body weight reduction to 18%, contrasting sharply with the plateau at 13% observed in the standard formulation administered daily (<i>p</i> < 0.05). Finally, dietary management, particularly time-restricted feeding, successfully maintained weight loss at ∼18% below baseline levels. Collectively, the combination of MNJI delivered sustained-release formulations and structured dietary protocols offers a promising and patient-friendly strategy for long-term obesity management, improving both adherence and therapeutic outcomes.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2557938"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of chitosan-based drug delivery systems in the treatment of bacterial diseases: a review.","authors":"Huan Huang, Yaxin Zhou, Jiehang Li, Zhijin Zhang, RongJia Han, Jingru Zuo, Yubin Bai, Jiyu Zhang","doi":"10.1080/10717544.2025.2514140","DOIUrl":"10.1080/10717544.2025.2514140","url":null,"abstract":"<p><p>Bacterial diseases are a significant challenge to human and animal health. The current treatment methods still have obvious shortcomings, such as poor targeting, low bioavailability, high side effects and drug resistance. Chitosan, with its outstanding biocompatibility, biodegradability, adhesiveness, antimicrobial properties, and ability to minimize drug side effects while improving bioavailability and therapeutic outcomes, serves as an ideal material for drug delivery systems, presenting a promising strategy for treating bacterial diseases. In this review, we briefly summarize the preparation methods of chitosan-based drug delivery systems and their application in the treatment of bacterial infections. The advantages of preparation of different types of chitosan-based drug delivery systems are discussed, supported by examples demonstrating their ability to improve drug antimicrobial activity, targeting, and bioavailability. Moreover, the current challenges, limitations, and future perspectives in this field were discussed, laying the groundwork for further development of chitosan-based drug delivery systems as high-performance and safe antimicrobial therapeutics.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2514140"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-03-04DOI: 10.1080/10717544.2025.2460671
Brett D Story, Sangwan Park, Karolina Roszak, Jaeho Shim, Monica Motta, Michelle Ferneding, Kayla M Rudeen, Andrew Blandino, Monica Ardon, Sophie Le, Leandro B C Teixeira, Glenn Yiu, William F Mieler, Sara M Thomasy, Jennifer J Kang-Mieler
{"title":"Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques.","authors":"Brett D Story, Sangwan Park, Karolina Roszak, Jaeho Shim, Monica Motta, Michelle Ferneding, Kayla M Rudeen, Andrew Blandino, Monica Ardon, Sophie Le, Leandro B C Teixeira, Glenn Yiu, William F Mieler, Sara M Thomasy, Jennifer J Kang-Mieler","doi":"10.1080/10717544.2025.2460671","DOIUrl":"10.1080/10717544.2025.2460671","url":null,"abstract":"<p><p>A clinical need exists for more effective intravitreal (IVT) drug delivery systems (DDS). This study tested the hypothesis that a novel biodegradable, injectable microsphere-hydrogel drug delivery system loaded with aflibercept (aflibercept-DDS) would exhibit long-term safety and biocompatibility in a non-human primate (NHP) model. We generated aflibercept-loaded poly (lactic-co-glycolic acid) microparticles with a modified double emulsion technique then embedded them into a biodegradable, thermo-responsive poly (ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide hydrogel. Aflibercept-DDS (50 µL, 15 µg) was injected into the right eye of 23 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP), corneal pachymetry, specular microscopy, A-scan biometry, streak retinoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and electroretinography (ERG) were performed monthly. Globes from 7 NHPs were histologically examined. Aflibercept-DDS was visualized in the vitreous up to 9 months post-IVT injection, slightly impeding fundoscopy in 4 of 23 eyes; no other consistent abnormalities were appreciated during ophthalmic examination. The IOP and total retinal thickness remained normal in all animals over all timepoints. Central corneal thickness, endothelial cell density, axial globe length, and refractive error did not significantly differ from baseline. Scotopic mixed rod-cone implicit times and amplitudes along with photopic cone response implicit times and amplitudes did not significantly differ from control values. No retinal or choroidal vascular abnormalities were detected with FA and normal retinal architecture was preserved using SD-OCT. Intravitreal injection of a biodegradable aflibercept-DDS was safe and well tolerated in NHPs up to 24 months.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2460671"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-04-01DOI: 10.1080/10717544.2025.2482195
Jie Chen, Enhui Ren, Ze Tao, Hongyu Lu, Yunchuan Huang, Jing Li, Yuzhe Chen, Zhuo Chen, Tianshan She, Hao Yang, Hong Zhu, Xiaofeng Lu
{"title":"Orchestrating T and NK cells for tumor immunotherapy via NKG2A-targeted delivery of a de novo designed IL-2Rβγ agonist.","authors":"Jie Chen, Enhui Ren, Ze Tao, Hongyu Lu, Yunchuan Huang, Jing Li, Yuzhe Chen, Zhuo Chen, Tianshan She, Hao Yang, Hong Zhu, Xiaofeng Lu","doi":"10.1080/10717544.2025.2482195","DOIUrl":"10.1080/10717544.2025.2482195","url":null,"abstract":"<p><p>As T and NK cell exhaustion is attributed to increased expression of immune checkpoints and decreased production of proliferative cytokines by these cells, immune checkpoint-targeted delivery of proliferative cytokines might induce robust and sustained antitumor immune responses. Here, the expression profile of NKG2A was first found to be narrower than that of PD-1 in tumor-infiltrated immune cells. Moreover, unlike PD-1, NKG2A was predominantly co-expressed with IL-2Rβγ in tumor-infiltrated CD8<sup>+</sup> T and NK cells, but not in Tregs, suggesting that NKG2A might be an ideal target for delivery of IL-2Rβγ agonists to overcome T and NK exhausting. For NKG2A-targeted delivery of an IL-2Rβγ agonist, a single molecule of de novo designed N215 endowed with Immunoglobin G(IgG)-binding ability was coupled to an antibody against NKG2A (αNKG2A) to produce αNKG2A-N215. NKG2A- and IL-2Rβγ-binding were well preserved in αNKG2A-N215, allowing αNKG2A-N215 to act as both an immune checkpoint inhibitor and a T and NK cell stimulator. Intravenously injected αNKG2A-N215 predominantly induced expansion of tumor-infiltrated CD8<sup>+</sup> T and NK cells while showing little stimulation of Tregs. Compared with the separate combination using αNKG2A and N215, αNKG2A-N215 exerted a greater antitumor effect in mice bearing MC38 or B16/F1 tumors. 50% of mice bearing MC38 tumors were cured by αNKG2A-N215, and long-term immunological memory against the tumor was induced in these mice. These results indicate that NKG2A is another ideal target for delivery of an IL-2Rβγ agonist, and αNKG2A-N215, with specificities for both NKG2A and IL-2Rβγ, might be developed as a novel agent for immunotherapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2482195"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-05-18DOI: 10.1080/10717544.2025.2505007
Jan L van der Hoek, Tess J Snoeijink, Hadi Mirgolbabaee, Romaine Kunst, Michel Versluis, Jutta Arens, Srirang Manohar, Erik Groot Jebbink
{"title":"Ultrasound contrast microbubbles to predict the microsphere distribution during transarterial radioembolization with holmium microspheres, an in vitro proof of concept study.","authors":"Jan L van der Hoek, Tess J Snoeijink, Hadi Mirgolbabaee, Romaine Kunst, Michel Versluis, Jutta Arens, Srirang Manohar, Erik Groot Jebbink","doi":"10.1080/10717544.2025.2505007","DOIUrl":"10.1080/10717544.2025.2505007","url":null,"abstract":"<p><p>Transarterial radioembolization (TARE) is an established treatment method for non-resectable liver tumors. One of the challenges of the approach is the accurate prediction of the microsphere biodistribution in the liver. We propose to use ultrasound contrast microbubbles as holmium microsphere precursors, which allows real-time prediction of the microsphere trajectories and biodistribution using dynamic contrast-enhanced ultrasound (DCE-US). The immediate goal in this in vitro study was to investigate the predictive capabilities of microbubbles as microsphere precursors. The study was conducted in an experimental in vitro model which represents the bifurcating right branch of the hepatic artery. A controlled injection of experimental BR-14 ultrasound contrast microbubbles and non-radioactive holmium-165 microspheres was performed in separate consecutive experiments in an arterial flow phantom. The microbubbles and microspheres were collected separately at the outlets of the phantom and counted using a Coulter counter to determine their distribution over the different outlets. The flow profile, the injection velocity, and the catheter position were monitored during the measurements to ensure stability. The results showed a good correlation between the microbubble and the microsphere distributions (p = 0.0038, r = 0.88) measured at the outlets. Differences in the distributions could be attributed to the characteristics of microbubbles and microspheres alone (e.g. particle size and concentration), since critical parameters were kept stable between the two experiments. The current in vitro study provides confidence that the microsphere biodistribution can be predicted using contrast microbubbles. The comparison provided by this study forms a foundation for the development of a DCE-US guided TARE treatment.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2505007"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}