Daniela Gabbia, Martina Colognesi, Antonella Grigoletto, Ilaria Zanotto, Tommaso Tedeschini, Benedetta Campara, Ken Hamura, Hiroki Yoshioka, Masaki Kamiya, Samantha Sarcognato, Sara De Martin, Gianfranco Pasut
{"title":"Conventional and hydrolysable PEGs: comparative evaluation of tissue accumulation, biodistribution and toxicological profile.","authors":"Daniela Gabbia, Martina Colognesi, Antonella Grigoletto, Ilaria Zanotto, Tommaso Tedeschini, Benedetta Campara, Ken Hamura, Hiroki Yoshioka, Masaki Kamiya, Samantha Sarcognato, Sara De Martin, Gianfranco Pasut","doi":"10.1039/d6bm00479b","DOIUrl":"10.1039/d6bm00479b","url":null,"abstract":"<p><p>PEG has been commonly considered safe and is widely used in pharmaceutical and personal care products. Concerns about its safety arised in relation to studies demonstrating its accumulation in some organs of animals treated with very high PEG dosages (<i>e.g.</i>, 200 mg per kg per week for up to 12 weeks). Although these dosages are substantially higher (200-100 000 times) than those of PEG-containing drugs, the concerns might still be valid for chronic therapies if the polymer is not cleared after the accumulation. In this study, in addition to investigate the phenomena of PEG accumulation/elimination and its effects on full blood count, plasma biochemistry and behavioral performance of treated animals, we also studied new hydrolysable PEGs (HyPEGs) for reducing PEG accumulation. HyPEGs contain a cleavable linker that, upon <i>in vivo</i> hydrolysis, lowers by half the size of the polymer. We here evaluated the <i>in vitro</i> effect of 20- and 40 kDa conventional PEGs on macrophages' phenotype in THP1 cells, and the potential <i>in vivo</i> toxicity, biodistribution, and vacuolation in liver, kidneys, spleen, choroid plexus, heart, and lungs of a small library of 20- and 40 kDa-conventional and hydrolysable PEGs, with both linear and branched structures, administered twice weekly for 12 weeks at the high dosage of 200 mg per kg per week followed by an 8-week washout period (no PEG administration). We demonstrated that PEG internalization by macrophages resulted in molecular weight-dependent cellular responses. <i>In vivo</i>, all PEGs accumulated in the liver, spleen, kidneys, and choroid plexus, and in general accumulation of HyPEGs was less evident. The 8-week washout period allowed for the clearance of most of the accumulated PEGs in all organs except for the kidneys, likely because the kidneys are the terminal organs for PEG elimination. Overall, all PEGs did not show any hematotoxicity by analyzing biochemical- and hematological-parameters. Cytoplasmic PEG-negative vacuoles were present in the choroid plexus, suggesting adaptive cellular responses, but no signs of neurotoxicity were observed. Our results indicate that, although the different PEGs elicited distinct macrophage responses <i>in vitro</i>, all hydrolysable PEGs showed limited tissue accumulation <i>in vivo</i> without signs of toxicity, highlighting their safety.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5488-5500"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899700","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":"US/ROS-responsive ALN-modified polymer nanoparticles enhance the efficacy of infiltration anesthesia through improved bone targeting and permeation.","authors":"Tu Huang, Yifei Ma, Xu Zhang, Zhuohao Zhang, Wanli Wang, Bowen Ke, Xinhua Liang","doi":"10.1039/d6bm00784h","DOIUrl":"10.1039/d6bm00784h","url":null,"abstract":"<p><p>Complex maxillofacial bone anatomy compromises the efficacy of local anesthetics. This study develops an ultrasound (US)/reactive oxygen species (ROS) cascade-responsive polylactic-coglycolic acid (PLGA) nanoparticle system for enhanced dental infiltration anesthesia and perioperative pain management. The nanoparticles, which were surface-modified with alendronate (ALN) <i>via</i> an ROS-cleavable thioketal (TK) linker and coloaded with bupivacaine (BUPI) and perfluorohexane (PFH), enabled enhanced bone targeting and penetration. Under US stimulation, PFH undergoes a liquid-gas phase transition, generating ROS that cleave TK linkers, switching the system from a \"bone-targeting\" to a \"bone-penetration\" state. This cascade mechanism facilitates deep tissue penetration of local anesthetics for enhanced anesthesia while enabling a dual-phase release profile: rapid US-triggered BUPI release for intraoperative analgesia and sustained diffusion for postoperative pain management. In rat models of tooth extraction and pulp injury, the system demonstrated superior efficacy over conventional BUPI, significantly increasing drug concentrations in the mandibular bone and improving pain-related outcomes. Biocompatibility was confirmed <i>via</i> histology and serum biomarkers. By overcoming maxillofacial bone barriers and enabling responsive, biphasic drug release, this platform represents a promising strategy to address the limitations of current local anesthetics in dentistry, reducing local anesthesia failure rates and improving perioperative pain control.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5475-5487"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885838","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":"Nanomicelles self-assembled using cyclosporine A-hyaluronic acid conjugates for dry eye disease treatment.","authors":"Zhenyi Lin, Mingrui Cheng, Haonan Cui, Yanmin Chen, Kai Jiang, Lijuan Zhu, Changhua Xu, Jiaxu Hong, Chuan Zhang","doi":"10.1039/d6bm00870d","DOIUrl":"10.1039/d6bm00870d","url":null,"abstract":"<p><p>Dry eye disease is a chronic inflammatory disorder of the ocular surface in which tear film instability and hyperosmolarity perpetuate a self-sustaining cycle of epithelial damage and inflammation; however, the therapeutic efficacy of topical cyclosporine A (CsA), a mainstay of treatment, is severely limited by rapid tear clearance and poor ocular bioavailability. Here, we developed a CsA-modified hyaluronic acid conjugate (HA-CsA) that spontaneously self-assembled into nanoparticles for topical DED therapy. HA-CsA nanomicelles (HCN) were synthesized through thiol-maleimide coupling and exhibited good dispersibility and stability in physiological media, with tear-compatible pH and osmolality. Under hyperosmotic stress, CD44 expression was upregulated in human corneal epithelial cells, and R6G-labeled HCN showed markedly enhanced cellular uptake compared with free R6G, indicating improved epithelial delivery. Functionally, HCN demonstrated greater cytocompatibility than free CsA and more effectively suppressed hyperosmotic stress-induced expression of IL-1β, IL-6, IL-8, TNF-α, and MMP-9. In a desiccating-stress mouse model of DED, topically administered HCN significantly improved corneal epithelial integrity, tear secretion and goblet cell survival while broadly attenuating inflammatory gene expression, macrophage activation and epithelial apoptosis, outperforming free cyclosporine A across all parameters. This conjugation-driven nanoplatform integrates tear film stabilization, targeted epithelial delivery and sustained local immunomodulation into a single, well-defined formulation, providing a promising translational strategy for interrupting the vicious inflammatory cycle that drives dry eye disease.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5519-5533"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011681","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":"A homologous cell membrane-camouflaged iridium-doped carbon dot nanozyme for multimodal imaging-guided radiosensitization.","authors":"Miaoqing Li, Ruiyang Zhang, Rui Cao, Yaning Xia, Mengyang Zhou, Yong Zhang, Yupeng Shi","doi":"10.1039/d6bm00762g","DOIUrl":"10.1039/d6bm00762g","url":null,"abstract":"<p><p>Radiotherapy (RT) is a mainstay of cancer treatment, yet its efficacy is limited by tumor hypoxia, elevated glutathione (GSH) levels, and a lack of tumor-specific radiosensitizers. Herein, we synthesized iridium-doped carbon dots (Ir-CDs) and further camouflaged them with 4T1 cancer cell membranes to construct a biomimetic nanoplatform (Ir-CDs@CM) integrating homologous targeting, multimodal imaging, and nanozyme-mediated properties for enhanced radiosensitization. The synthesized Ir-CDs exhibited a uniform size of ∼2.25 nm and good water dispersibility. After encapsulation with 4T1 cell membranes, Ir-CDs@CM showed an average hydrodynamic diameter of ∼181.9 nm and a zeta potential of -17.0 mV, along with excellent colloidal stability, low cytotoxicity, favorable biocompatibility, and homologous targeting capability. Functionally, Ir-CDs@CM enabled dual-mode fluorescence (FL) and computed tomography (CT) imaging. Moreover, Ir-CDs displayed three nanozyme activities: GSH-depletion activity (47.13% GSH depletion), catalase-like activity (O<sub>2</sub> generation up to 11.9 mg L<sup>-1</sup>), and peroxidase-like activity (a 5.17-fold increase in reactive oxygen species (ROS) generation under X-ray irradiation). This nanozyme-mediated oxygen evolution and ROS generation reduced 4T1 cell viability from 83% to 45.69% under 6 Gy irradiation. <i>In vivo</i>, the nanoplatform achieved excellent tumor accumulation and therapeutic efficacy in subcutaneous tumor-bearing mice, suppressing tumor growth within 14 days. Body weight fluctuations remained below 5% with no hepatorenal toxicity or tissue damage, confirming excellent biosafety. This strategy integrates membrane camouflage with iridium-based nanozyme technology for targeted imaging, microenvironment modulation, and radiosensitization, opening new avenues for integrated tumor therapy and diagnosis.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5501-5518"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899711","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}
Hongwei Chen, Zheng Zhang, Xinghui Lai, Zhihao Wang, Xianzhu Yang, Jinzhi Du, Xiaojiao Du
{"title":"Tumor-specific <i>in situ</i> IL-12 expression combined with αPD-L1 suppresses melanoma growth by remodeling the tumor immune microenvironment.","authors":"Hongwei Chen, Zheng Zhang, Xinghui Lai, Zhihao Wang, Xianzhu Yang, Jinzhi Du, Xiaojiao Du","doi":"10.1039/d6bm00788k","DOIUrl":"10.1039/d6bm00788k","url":null,"abstract":"<p><p>Interleukin-12 (IL-12) potently activates antitumor immune responses and compensates for the challenge of insufficient T cell activation and infiltration faced in immune checkpoint therapy. However, its clinical application is limited by severe systemic toxicity and the upregulation of PD-L1 on tumor cells during treatment. Here, we developed iLAN<sub>pTyr-IL-12</sub>, a lipid-assisted nanoparticle system loaded with tyrosinase (Tyr) promoter-driven IL-12 plasmids, designed to achieve specific and sustained IL-12 expression exclusively in melanoma cells. The secreted IL-12 promoted dendritic cell maturation, T cell activation and proliferation, and IFN-γ secretion. Notably, iLAN<sub>pTyr-IL-12</sub> treatment upregulated PD-L1 expression on tumor cells, suggesting a negative feedback loop that supports the rationale for combination with anti-PD-L1 (αPD-L1). In a subcutaneous B16-F10 melanoma model, iLAN<sub>pTyr-IL-12</sub> monotherapy significantly enhanced tumor suppression and increased intratumoral infiltration of T cells and NKT cells, along with a decreased M2/M1 macrophage ratio. When combined with αPD-L1, it produced an enhanced antitumor effect, achieved a tumor growth inhibition rate of 83% and further augmented intratumoral CD8<sup>+</sup> T cell infiltration. Additionally, no significant systemic toxicity or organ damage was observed. Collectively, these findings demonstrate that iLAN<sub>pTyr-IL-12</sub> enables tumor-specific IL-12 expression and, when combined with αPD-L1, provides a promising cytokine-immune checkpoint combination immunotherapy with reduced off-target toxicity.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5430-5441"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862655","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}
Jiahuiyu Fang, Shuting Zhang, Pranab Sarker, Xiaoxue Qin, Mark J Uline, Tao Wei
{"title":"Bio-nano hybrids: molecular interactions between iron oxide nanoparticles and outer-membrane extracellular cytochromes of <i>Shewanella oneidensis</i>.","authors":"Jiahuiyu Fang, Shuting Zhang, Pranab Sarker, Xiaoxue Qin, Mark J Uline, Tao Wei","doi":"10.1039/d6bm01152g","DOIUrl":"10.1039/d6bm01152g","url":null,"abstract":"<p><p>Metal oxide nanoparticles (NPs) coupled with dissimilatory metal-reducing bacteria enable continuous redox cycling through extracellular electron transfer (ET), a process central to bioremediation and bioenergy applications. However, the molecular mechanisms governing ET at the outer membrane-iron oxide NP interface remain unclear. Here, atomistic molecular dynamics simulations were employed to elucidate how the extracellular cytochromes of <i>Shewanella oneidensis</i> cooperatively mediate iron oxide NP adsorption, a prerequisite for extracellular ET. Our study shows that MtrF and two OmcA decaheme cytochromes are asymmetrically associated through their N- and C-terminal regions with distinct interaction energies, and their terminal heme groups (heme 10) of the long chains in the staggered cross-heme networks are connected to form a continuous heme network. This assembly sterically occludes MtrF heme 10 and redirects NP adsorption to alternative termini of the cross-heme network, including heme 5 (the opposite end of the long heme chain), where MtrF mediates binding through electrostatic interactions involving its heme groups and surface residues. NP adsorption also occurs near heme 2 at the terminus of the MtrF short heme chain, where OmcA residues primarily stabilize NP attachment. These results identify MtrF as the primary mediator of extracellular ET and establish OmcA as an interfacial stabilizer that enhances NP binding without directly mediating ET.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5548-5558"},"PeriodicalIF":6.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014828","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":"A nucleus-targeting type-I photosensitive nanoplatform for DNA-binding-enhanced photodynamic therapy.","authors":"Zhiqiang Zhang, Wenchen Wang, Zhe Guo, Yunchan Zhao, Jimeng Wang, Xuefei Yuan, Jia Tian","doi":"10.1039/d6bm00994h","DOIUrl":"https://doi.org/10.1039/d6bm00994h","url":null,"abstract":"<p><p>Photodynamic therapy (PDT), as a promising anticancer strategy, has attracted much attention due to the advantages of non-invasiveness, temporal-spatial selectivity, and low tendency to induce drug resistance. However, the clinical translation of PDT faces severe challenges, owing to the oxygen-demanding nature of ROS generation and the ultrashort lifespan and narrow diffusion radius of ROS. Herein, we report a nanoplatform that integrates a tumor microenvironment (TME)-responsive polymeric vehicle with an aggregation-induced emission (AIE) type-I photosensitizer (TD) with nucleus-targeting and DNA-binding abilities. This nanoplatform enables specific delivery in the acidic and GSH-overexpressed TME <i>via</i> pH/redox dual responsiveness, ensuring selective accumulation and low off-target effects. By mimicking the nucleus-targeting chemical structure of Hoechst, TD can penetrate the nuclear envelope, intercalate DNA, and generate hydroxyl radicals and superoxide anion radicals near genetic materials, causing DNA damage and apoptosis even under hypoxia. <i>In vitro</i> and <i>in vivo</i> studies confirmed the effective ROS generation, antitumor efficacy, and good biocompatibility of the nanoplatform. The DNA-binding-enhanced PDT strategy provides a promising pathway for precision phototherapeutics.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100967","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}
Litao Yao, Yuanhao Tong, Xiaohong Lin, Mengmeng Huang, Li Li, Jing Jiang, Xinwei Jiang, Haiyan Wang
{"title":"Tailoring the biological performance of titanium implants <i>via</i> a TaCu nanocoating on MAO-porous layers: the interplay between surface topography and controlled Cu<sup>2+</sup> release.","authors":"Litao Yao, Yuanhao Tong, Xiaohong Lin, Mengmeng Huang, Li Li, Jing Jiang, Xinwei Jiang, Haiyan Wang","doi":"10.1039/d6bm00600k","DOIUrl":"https://doi.org/10.1039/d6bm00600k","url":null,"abstract":"<p><p>Titanium (Ti) is widely used in oral implants but is limited by insufficient osteogenic activity, angiogenic capacity, and antibacterial performance. To address this, pure Ti was modified by micro-arc oxidation (MAO) to form a porous layer, followed by magnetron sputtering of a TaCu nanocoating under different conditions to prepare three composite samples (MAO-Ti/TaCu1, MAO-Ti/TaCu4, and MAO-Ti/TaCu7). The samples were characterized for surface properties and Cu<sup>2+</sup> release, and their biological performance was evaluated <i>via in vitro</i> experiments. Results showed that MAO-Ti/TaCu coatings maintained the MAO porous structure and achieved cytocompatible, sustained Cu<sup>2+</sup> release. MAO-Ti/TaCu4 exhibited optimal osteogenic activity, with the highest cell viability, ALP activity, matrix mineralization, and expression of osteogenic-related genes (ALP, Runx2, Col-I, and OPN). MAO-Ti/TaCu7 showed the strongest angiogenic capacity, reflected by superior HUVEC morphology, migration, and angiogenic-related gene (eNOS, VEGF, and FGFR1) expression. All TaCu-modified groups had significant antibacterial activity. The enhanced performance was attributed to the synergistic effect of the porous MAO layer and TaCu nanocoating, with moderate Cu<sup>2+</sup> release favoring osteogenesis and higher release promoting angiogenesis. This study provides a new strategy for titanium implant surface modification to improve osseointegration.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100984","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":"Ultrasound-responsive chitosan-based hydrogels for intravesical chemotherapy: mechanisms, design strategies, and translational perspectives.","authors":"Jyoti Yadav, Jaiveer Singh, Raviraj Vankayala, Gautam Ram Choudhary","doi":"10.1039/d6bm01081d","DOIUrl":"https://doi.org/10.1039/d6bm01081d","url":null,"abstract":"<p><p>Intravesical therapy remains the standard treatment for non-muscle-invasive bladder cancer (NMIBC), yet its clinical efficacy is limited by significant biological, pharmacological, and procedural barriers. Conventional intravesical drug instillation requires repeated hospital visits and urethral catheterization, which may reduce patient compliance owing to discomfort, urethral trauma, and an increased risk of urinary tract infections. Therapeutic performance is further compromised by rapid drug dilution, frequent bladder emptying, and the dynamic urinary environment, resulting in a short intravesical residence time. Biological barriers, including the exceptionally tight urothelial permeability barrier (transepithelial electrical resistance >10 000 Ω cm<sup>2</sup>), comparable to the blood-brain barrier, and the hypoxic tumour microenvironment, further restrict drug penetration, leaving less than 5% of the administered dose available at the tumour site. Escalating drug concentrations to compensate for poor penetration frequently results in chemical cystitis and other local adverse effects. Among emerging biomaterials, chitosan has attracted considerable attention owing to its excellent mucoadhesive properties, transient modulation of urothelial tight junctions, favourable biocompatibility, and biodegradability, making it an attractive platform for prolonged intravesical drug retention. Genipin has emerged as the most widely investigated natural crosslinker because of its low cytotoxicity, tunable crosslinking properties, and ability to improve the mechanical stability and sustained-release behaviour of chitosan hydrogels. Integration of ultrasound as a non-invasive external stimulus, particularly through microbubble-mediated cavitation and sonoporation, further enables spatiotemporally controlled drug release and enhanced urothelial permeability. In this review, we critically discuss the biological barriers to intravesical drug delivery and highlight recent advances in ultrasound-responsive chitosan-genipin hydrogels as multifunctional platforms for NMIBC therapy. We evaluate crosslinker safety, strategies for overcoming tumour hypoxia, and preclinical evidence demonstrating prolonged bladder retention (>72 h), 2-3-fold enhanced tissue penetration, and tumour inhibition of 60-80%. Finally, we discuss key translational challenges, including scalable manufacturing, regulatory considerations, patient heterogeneity, and long-term safety, while outlining future opportunities in theranostic hydrogels, microrobots, closed-loop drug delivery, and multi-stimuli-responsive biomaterials. Collectively, ultrasound-responsive chitosan-genipin hydrogels represent a promising intravesical platform capable of enhancing therapeutic efficacy while minimizing treatment-related toxicity in NMIBC.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078986","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}
Ellise Kurczewski, Aslan Mansurov, Chirag Sachar, Mustafa O Guler
{"title":"Advances in the development and delivery of nucleic acid-based therapeutics.","authors":"Ellise Kurczewski, Aslan Mansurov, Chirag Sachar, Mustafa O Guler","doi":"10.1039/d6bm00738d","DOIUrl":"10.1039/d6bm00738d","url":null,"abstract":"<p><p>Recent advancements in experimental and computational methods along with growing gene sequencing libraries have enabled rapid development of nucleic acid-based therapeutic design for a wide variety of diseases. New drugs, delivery tools and methods have enabled precise and efficient therapy at a molecular scale. This review covers the current landscape and future directions of methods for gene and cell therapies, as well as their applications, advantages, and limitations. We present self-amplifying RNA, circular RNA, CRISPR systems, antisense oligonucleotides, and antibody-oligonucleotide conjugates, as well as CAR modification of T-cells, natural killer cells, and macrophages, with a brief discussion of modified stem cells. We also discuss developments in viral and non-viral delivery systems for their applications in cell and gene therapies.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5131-5156"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816757","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}