Min Zhang, Miao Qiu, Zengkun Li, Rui Xu, Yao Wang, Wei Wang, Christopher D Snow, Matt J Kipper, Laurence A Belfiore, Jianguo Tang
Protein crystals have advantageous properties as framework materials, such as porosity and organized, high-density functional groups with the potential for guest specificity. Thus, protein crystal materials open up vast opportunities for fluorescent species doping and drug sensing. In this work, we explore this frontier by combining two lanthanide complexes with hen egg white lysozyme (HEWL) and directly obtaining co deposited structures in one step using an anti-solvent method different from the previous two-step method. Cross-linking of the protein was achieved using glutaraldehyde, ensuring the stability of the assembly in diverse solvent environments. The use of glutaraldehyde achieved protein cross-linking, ensuring the stability of the components in various solvent environments, including no leakage of fluorescent substances in ultrapure water and anhydrous ethanol. Differential fluorescence quenching effects of amino acids on the two doped luminescent complexes were observed. Introduction of amino acids, varying in concentration and type, resulted in distinct fluorescence enhancement or quenching effects on the protein assembly loaded with the complexes, and the detection results are reflected through different fitting equations and parameters. By exploring the application of this hybrid material for amino acid detection, this work lays the groundwork for broader applications.
{"title":"Luminescent bio-sensors <i>via</i> co-assembly of hen egg white lysozyme with Eu<sup>3+</sup>/Tb<sup>3+</sup>-complexes.","authors":"Min Zhang, Miao Qiu, Zengkun Li, Rui Xu, Yao Wang, Wei Wang, Christopher D Snow, Matt J Kipper, Laurence A Belfiore, Jianguo Tang","doi":"10.1039/d4tb01766h","DOIUrl":"https://doi.org/10.1039/d4tb01766h","url":null,"abstract":"<p><p>Protein crystals have advantageous properties as framework materials, such as porosity and organized, high-density functional groups with the potential for guest specificity. Thus, protein crystal materials open up vast opportunities for fluorescent species doping and drug sensing. In this work, we explore this frontier by combining two lanthanide complexes with hen egg white lysozyme (HEWL) and directly obtaining co deposited structures in one step using an anti-solvent method different from the previous two-step method. Cross-linking of the protein was achieved using glutaraldehyde, ensuring the stability of the assembly in diverse solvent environments. The use of glutaraldehyde achieved protein cross-linking, ensuring the stability of the components in various solvent environments, including no leakage of fluorescent substances in ultrapure water and anhydrous ethanol. Differential fluorescence quenching effects of amino acids on the two doped luminescent complexes were observed. Introduction of amino acids, varying in concentration and type, resulted in distinct fluorescence enhancement or quenching effects on the protein assembly loaded with the complexes, and the detection results are reflected through different fitting equations and parameters. By exploring the application of this hybrid material for amino acid detection, this work lays the groundwork for broader applications.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kalindu Perera, Moez Ghumman, Parand Sorkhdini, Carmelissa Norbrun, Seraphina Negash, Yang Zhou, Jyothi U Menon
Pulmonary fibrosis (PF) is a chronic interstitial disorder of the respiratory system that can be debilitating as it progresses and has experienced a slow rise in incidence in past years. Treatment is complicated by the complex aetiology of the disease and the off-target effects of the two FDA-approved therapeutics available on the market: pirfenidone and nintedanib. In this work, we propose a multipurpose nanoparticle system consisting of poly(lactic-co-glycolic) acid polymer (PLGA) and a coating of citrus pectin (CP) for galectin-3 targeting and anti-fibrotic therapy. Pectin from citrus peels has been observed to have anti-fibrotic activity in a range of fibrotic tissues, causing a decrease in the expression and activity of galectin-3: a key, upregulated marker of fibrosis. We show that the CP-PLGA nanoparticles (NPs) have an average diameter of 340.5 ± 10.6 nm, compatible with inhalation and retention in the deep lung, and that CP constitutes, on average, 40.3% of the final CP-PLGA formulation. The NPs are well-tolerated by MRC-5 lung fibroblasts up to 2 mg mL-1. We demonstrate the NPs' ability to target transforming growth factor β (TGFβ)-treated fibrotic MRC-5 cells in a specific, dose-dependent manner, saturating at approx. 250 μg mL-1in vitro, and that our NPs have potent anti-fibrotic activity in vivo in particular, reversing bleomycin-induced fibrosis in mouse lungs, accompanied by marked reduction in profibrotic markers including collagen 1, fibronectin, α-smooth muscle actin, β-catenin and galectin-3. In all, we present an inherently therapeutic inhalable nanocarrier for galectin-3 targeting and anti-fibrotic therapy. We envision this carrier to be doubly effective against fibrotic lung tissue when combined with an encapsulated anti-fibrotic drug, improving overall/total therapeutic efficacy and patient compliance via the reduction of off-target effects and additive therapeutic effects.
{"title":"Citrus pectin-coated inhalable PLGA nanoparticles for treatment of pulmonary fibrosis.","authors":"Kalindu Perera, Moez Ghumman, Parand Sorkhdini, Carmelissa Norbrun, Seraphina Negash, Yang Zhou, Jyothi U Menon","doi":"10.1039/d4tb01682c","DOIUrl":"10.1039/d4tb01682c","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a chronic interstitial disorder of the respiratory system that can be debilitating as it progresses and has experienced a slow rise in incidence in past years. Treatment is complicated by the complex aetiology of the disease and the off-target effects of the two FDA-approved therapeutics available on the market: pirfenidone and nintedanib. In this work, we propose a multipurpose nanoparticle system consisting of poly(lactic-<i>co</i>-glycolic) acid polymer (PLGA) and a coating of citrus pectin (CP) for galectin-3 targeting and anti-fibrotic therapy. Pectin from citrus peels has been observed to have anti-fibrotic activity in a range of fibrotic tissues, causing a decrease in the expression and activity of galectin-3: a key, upregulated marker of fibrosis. We show that the CP-PLGA nanoparticles (NPs) have an average diameter of 340.5 ± 10.6 nm, compatible with inhalation and retention in the deep lung, and that CP constitutes, on average, 40.3% of the final CP-PLGA formulation. The NPs are well-tolerated by MRC-5 lung fibroblasts up to 2 mg mL<sup>-1</sup>. We demonstrate the NPs' ability to target transforming growth factor β (TGFβ)-treated fibrotic MRC-5 cells in a specific, dose-dependent manner, saturating at approx. 250 μg mL<sup>-1</sup><i>in vitro</i>, and that our NPs have potent anti-fibrotic activity <i>in vivo</i> in particular, reversing bleomycin-induced fibrosis in mouse lungs, accompanied by marked reduction in profibrotic markers including collagen 1, fibronectin, α-smooth muscle actin, β-catenin and galectin-3. In all, we present an inherently therapeutic inhalable nanocarrier for galectin-3 targeting and anti-fibrotic therapy. We envision this carrier to be doubly effective against fibrotic lung tissue when combined with an encapsulated anti-fibrotic drug, improving overall/total therapeutic efficacy and patient compliance <i>via</i> the reduction of off-target effects and additive therapeutic effects.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Longkang Li, Huipeng Li, Zhentian Diao, Huan Zhou, Yanjie Bai, Lei Yang
Correction for 'Development of a tannic acid- and silicate ion-functionalized PVA-starch composite hydrogel for in situ skeletal muscle repairing' by Longkang Li et al., J. Mater. Chem. B, 2024, 12, 3917-3926, https://doi.org/10.1039/D3TB03006G.
{"title":"Correction: Development of a tannic acid- and silicate ion-functionalized PVA-starch composite hydrogel for <i>in situ</i> skeletal muscle repairing.","authors":"Longkang Li, Huipeng Li, Zhentian Diao, Huan Zhou, Yanjie Bai, Lei Yang","doi":"10.1039/d5tb90025e","DOIUrl":"https://doi.org/10.1039/d5tb90025e","url":null,"abstract":"<p><p>Correction for 'Development of a tannic acid- and silicate ion-functionalized PVA-starch composite hydrogel for <i>in situ</i> skeletal muscle repairing' by Longkang Li <i>et al.</i>, <i>J. Mater. Chem. B</i>, 2024, <b>12</b>, 3917-3926, https://doi.org/10.1039/D3TB03006G.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Wang, Yanfang Sun, Han Wang, Tianqi Liu, Amin Shavandi, Lei Nie, Khaydar E Yunusov, Guohua Jiang
Correction for 'Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management' by Rui Wang et al., J. Mater. Chem. B, 2024, 12, 1064-1076, https://doi.org/10.1039/D3TB02607H.
{"title":"Correction: Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management.","authors":"Rui Wang, Yanfang Sun, Han Wang, Tianqi Liu, Amin Shavandi, Lei Nie, Khaydar E Yunusov, Guohua Jiang","doi":"10.1039/d5tb90023a","DOIUrl":"https://doi.org/10.1039/d5tb90023a","url":null,"abstract":"<p><p>Correction for 'Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management' by Rui Wang <i>et al.</i>, <i>J. Mater. Chem. B</i>, 2024, <b>12</b>, 1064-1076, https://doi.org/10.1039/D3TB02607H.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retraction of 'Growth factors regional patterned and photoimmobilized scaffold applied to bone tissue regeneration' by Ling-Kun Zhang et al., J. Mater. Chem. B, 2020, 8, 10990-11000, https://doi.org/10.1039/D0TB02317E.
Katsuya Komiyama, Maya Allard, Corentin Eschenbrenner, Clémence Sicard, Ahmed Hamraoui, Francisco M Fernandes
Water-stable macroporous hydrogels, inspired by the structural and chemical characteristics of plant stems, are expected to open a wide range of possibilities in soft materials for passive liquid transport. However, obtaining efficient materials for these applications still poses a major challenge due to the complexity of shaping hydrogels at the relevant scale-length. Here, water-stable macroporous hydrogels were fabricated using alginate and TEMPO-oxidized cellulose via a new approach involving ice templating and topotactic ion-crosslinking with Ca2+. This approach fully avoids the energy-intensive lyophilization process and results in composite hydrogels with pore sizes akin to those found in celery xylem, a model we chose for plant stems. Importantly, the pore size could be tailored by adjusting both the ice-growth velocities and the ratios of alginate to oxidized cellulose. The resulting hydrogels displayed remarkable water stability along with viscoelastic properties and wettability that depend on the alginate and oxidized cellulose ratios. Mechanical properties, such as compression stress and toughness, consistently increased with higher alginate contents. In addition, liquid transport measurements on crosslinked hydrogels with varying compositions and ice growth velocities revealed rising speeds comparable to those observed in celery, confirming the ability of polysaccharide-based hydrogels obtained by ice templating and topotactic crosslinking as relevant materials to mimic the function of plant stems. Due to their intrinsic biocompatibility, the materials presented here offer significant potential for developing soft liquid transport systems suited for biological settings, with promising applications in both environmental and bioengineering fields.
{"title":"Ice templating water-stable macroporous polysaccharide hydrogels to mimic plant stems.","authors":"Katsuya Komiyama, Maya Allard, Corentin Eschenbrenner, Clémence Sicard, Ahmed Hamraoui, Francisco M Fernandes","doi":"10.1039/d4tb02204a","DOIUrl":"https://doi.org/10.1039/d4tb02204a","url":null,"abstract":"<p><p>Water-stable macroporous hydrogels, inspired by the structural and chemical characteristics of plant stems, are expected to open a wide range of possibilities in soft materials for passive liquid transport. However, obtaining efficient materials for these applications still poses a major challenge due to the complexity of shaping hydrogels at the relevant scale-length. Here, water-stable macroporous hydrogels were fabricated using alginate and TEMPO-oxidized cellulose <i>via</i> a new approach involving ice templating and topotactic ion-crosslinking with Ca<sup>2+</sup>. This approach fully avoids the energy-intensive lyophilization process and results in composite hydrogels with pore sizes akin to those found in celery xylem, a model we chose for plant stems. Importantly, the pore size could be tailored by adjusting both the ice-growth velocities and the ratios of alginate to oxidized cellulose. The resulting hydrogels displayed remarkable water stability along with viscoelastic properties and wettability that depend on the alginate and oxidized cellulose ratios. Mechanical properties, such as compression stress and toughness, consistently increased with higher alginate contents. In addition, liquid transport measurements on crosslinked hydrogels with varying compositions and ice growth velocities revealed rising speeds comparable to those observed in celery, confirming the ability of polysaccharide-based hydrogels obtained by ice templating and topotactic crosslinking as relevant materials to mimic the function of plant stems. Due to their intrinsic biocompatibility, the materials presented here offer significant potential for developing soft liquid transport systems suited for biological settings, with promising applications in both environmental and bioengineering fields.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SeongHoon Jo, Yu-Jin Kim, Taek Hwang, Se Youn Jang, So-Jin Park, Seongryeol Ye, Youngmee Jung, Jin Yoo
Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by the progressive degeneration of retinal cells, particularly retinal pigment epithelial (RPE) cells. Conventional treatments primarily focus on slowing disease progression without providing a cure. Recent advances in tissue engineering and cell-based therapies offer promising avenues for regenerating retinal tissue and restoring vision. In this study, we developed ultrathin, nanoporous membrane scaffolds designed to mimic Bruch's membrane (BrM) for RPE cell transplantation using vapor-induced phase separation. These scaffolds, fabricated from a blend of poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(lactic-co-glycolic acid) (PLGA), exhibited favorable topography, biocompatibility, and shape-memory properties. In vitro experiments confirmed that the nanoporous topography effectively supports the formation of RPE monolayers with intact tight junctions. Additionally, the shape-memory characteristic enables the membrane to self-expand at body temperature (37 °C), facilitating minimally invasive delivery via injection. ARPE-19 cell-attached nanothin membranes successfully demonstrated shape-recovery properties and were deliverable through a catheter in an ex vivo model. Our findings suggest that the developed scaffolds provide a promising approach for retinal tissue engineering and could significantly contribute to advanced treatments for AMD and other retinal degenerative diseases.
{"title":"Injectable ultrathin porous membranes harnessing shape memory polymers for retinal tissue engineering.","authors":"SeongHoon Jo, Yu-Jin Kim, Taek Hwang, Se Youn Jang, So-Jin Park, Seongryeol Ye, Youngmee Jung, Jin Yoo","doi":"10.1039/d4tb02287d","DOIUrl":"https://doi.org/10.1039/d4tb02287d","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by the progressive degeneration of retinal cells, particularly retinal pigment epithelial (RPE) cells. Conventional treatments primarily focus on slowing disease progression without providing a cure. Recent advances in tissue engineering and cell-based therapies offer promising avenues for regenerating retinal tissue and restoring vision. In this study, we developed ultrathin, nanoporous membrane scaffolds designed to mimic Bruch's membrane (BrM) for RPE cell transplantation using vapor-induced phase separation. These scaffolds, fabricated from a blend of poly(L-lactide-<i>co</i>-ε-caprolactone) (PLCL) and poly(lactic-<i>co</i>-glycolic acid) (PLGA), exhibited favorable topography, biocompatibility, and shape-memory properties. <i>In vitro</i> experiments confirmed that the nanoporous topography effectively supports the formation of RPE monolayers with intact tight junctions. Additionally, the shape-memory characteristic enables the membrane to self-expand at body temperature (37 °C), facilitating minimally invasive delivery <i>via</i> injection. ARPE-19 cell-attached nanothin membranes successfully demonstrated shape-recovery properties and were deliverable through a catheter in an <i>ex vivo</i> model. Our findings suggest that the developed scaffolds provide a promising approach for retinal tissue engineering and could significantly contribute to advanced treatments for AMD and other retinal degenerative diseases.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiuping Wan, Caijie Zhang, Pengyu Lei, Hanbing Wang, Rongbing Chen, Qinsi Yang, Yongwei Cheng, Wei Wu, Da Sun, Xiaofei Hong
Inflammatory bowel disease (IBD) is a severe chronic intestinal disorder with a rising global incidence. Current therapies, including the delivery of anti-inflammatory drugs and probiotics, face significant challenges in terms of safety, stability, and efficacy. In IBD patients, the activity of antioxidant enzymes (e.g., superoxide dismutase, glutathione peroxidase, and glutathione reductase) is reduced at the site of intestinal inflammation, leading to the accumulation of reactive oxygen species (ROS). This accumulation damages the intestinal mucosa, disrupts tight junctions between cells, and compromises the integrity of the intestinal barrier, exacerbating IBD symptoms. Therefore, nanoparticles responsive to ROS and capable of mimicking antioxidant enzyme activity, such as boronates, polydopamine, sulfides, and metal nanozymes, have emerged as promising tools. These nanoparticles can respond to elevated ROS levels in inflamed intestinal regions and release drugs to effectively neutralize ROS, making them ideal candidates for IBD treatment. This review discusses the application of various ROS-responsive nanomaterial delivery systems in IBD therapy, highlights current challenges, and outlines future research directions. Furthermore, we explore the "layered programmable delivery" strategy, which combines ROS-responsive nanoparticles with pH-responsive and cell membrane-targeted nanoparticles. This strategy has the potential to overcome the limitations of single-mechanism targeted drug delivery, enabling multi-range and multi-functional treatment approaches that significantly enhance delivery efficiency, providing new insights for the future of localized IBD treatment.
{"title":"Precision therapeutics for inflammatory bowel disease: advancing ROS-responsive nanoparticles for targeted and multifunctional drug delivery.","authors":"Xiuping Wan, Caijie Zhang, Pengyu Lei, Hanbing Wang, Rongbing Chen, Qinsi Yang, Yongwei Cheng, Wei Wu, Da Sun, Xiaofei Hong","doi":"10.1039/d4tb02868f","DOIUrl":"https://doi.org/10.1039/d4tb02868f","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a severe chronic intestinal disorder with a rising global incidence. Current therapies, including the delivery of anti-inflammatory drugs and probiotics, face significant challenges in terms of safety, stability, and efficacy. In IBD patients, the activity of antioxidant enzymes (<i>e.g.</i>, superoxide dismutase, glutathione peroxidase, and glutathione reductase) is reduced at the site of intestinal inflammation, leading to the accumulation of reactive oxygen species (ROS). This accumulation damages the intestinal mucosa, disrupts tight junctions between cells, and compromises the integrity of the intestinal barrier, exacerbating IBD symptoms. Therefore, nanoparticles responsive to ROS and capable of mimicking antioxidant enzyme activity, such as boronates, polydopamine, sulfides, and metal nanozymes, have emerged as promising tools. These nanoparticles can respond to elevated ROS levels in inflamed intestinal regions and release drugs to effectively neutralize ROS, making them ideal candidates for IBD treatment. This review discusses the application of various ROS-responsive nanomaterial delivery systems in IBD therapy, highlights current challenges, and outlines future research directions. Furthermore, we explore the \"layered programmable delivery\" strategy, which combines ROS-responsive nanoparticles with pH-responsive and cell membrane-targeted nanoparticles. This strategy has the potential to overcome the limitations of single-mechanism targeted drug delivery, enabling multi-range and multi-functional treatment approaches that significantly enhance delivery efficiency, providing new insights for the future of localized IBD treatment.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although sonodynamic therapy (SDT) has shown promising advancements in combination with chemotherapy, it frequently necessitates the requirement of conventional sonosensitizers and chemotherapeutic agents, engendering intricate systems and potential drug resistance. Herein, we fabricated a potent Pt(IV)-poly(amino acid) coordination nanosonosensitizer (PHPt) with dual reversal of cisplatin resistance, producing abundant 1O2 and ˙OH upon ultrasound irradiation without the use of any external sonosensitizers. The Pt(IV) prodrug in PHPt efficiently reduced to cisplatin through SDT-induced ˙H and glutathione (GSH), inducing ˙OH accumulation and CDDP release, which further amplified the oxidative stress on SDT. Moreover, the high GSH depletion performance of PHPt and administration of aspirin effectively inhibited cisplatin detoxification and activation of the nuclear factor-kappa B pathway, respectively. This cooperative action between the Pt(IV) prodrug and SDT in the tumor microenvironment promoted self-cyclic amplification of sonodynamic-chemotherapy, achieving a significant tumor inhibition rate of 99.4%. Thus, this study offers novel perspectives on the sonosensitizer development and cisplatin application in SDT.
{"title":"Pt(IV) prodrug as a potent nanosonosensitizer self-cyclically amplifies sonodynamic-chemotherapy with dually reversing cisplatin resistance.","authors":"Wenxin Li, Ziyi Lin, Jiahui Liu, Jiarui Zhang, Yuxuan Li, Yian Liu, Xinru Yuan, Huimin Li, Heyun Shen","doi":"10.1039/d4tb02615b","DOIUrl":"https://doi.org/10.1039/d4tb02615b","url":null,"abstract":"<p><p>Although sonodynamic therapy (SDT) has shown promising advancements in combination with chemotherapy, it frequently necessitates the requirement of conventional sonosensitizers and chemotherapeutic agents, engendering intricate systems and potential drug resistance. Herein, we fabricated a potent Pt(IV)-poly(amino acid) coordination nanosonosensitizer (PHPt) with dual reversal of cisplatin resistance, producing abundant <sup>1</sup>O<sub>2</sub> and ˙OH upon ultrasound irradiation without the use of any external sonosensitizers. The Pt(IV) prodrug in PHPt efficiently reduced to cisplatin through SDT-induced ˙H and glutathione (GSH), inducing ˙OH accumulation and CDDP release, which further amplified the oxidative stress on SDT. Moreover, the high GSH depletion performance of PHPt and administration of aspirin effectively inhibited cisplatin detoxification and activation of the nuclear factor-kappa B pathway, respectively. This cooperative action between the Pt(IV) prodrug and SDT in the tumor microenvironment promoted self-cyclic amplification of sonodynamic-chemotherapy, achieving a significant tumor inhibition rate of 99.4%. Thus, this study offers novel perspectives on the sonosensitizer development and cisplatin application in SDT.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanadium is a bioactive trace element with variable valence. Its pentavalent form has been confirmed to be capable of predominantly regulating the early and mid-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without tumor inhibition, while its tetravalent form exhibits tumor inhibition but only primarily modulates late osteogenic differentiation and angiogenesis. In this study, a multifunctional bone tissue scaffold consisting of mixed-valence vanadium-doped mesoporous bioactive glass and poly(lactic-co-glycolic acid) (V(IV/V)-MBG/PLGA) was developed to simultaneously inhibit the recurrence of osteosarcoma and promote the regeneration of operative bone defects. The in vitro results showed that the V(IV) and V(V) species could be sustainably released from V(IV/V)-MBG and complementarily enhance the proliferation, osteogenic differentiation, and mineralization of BMSCs by activating multiple signaling pathways throughout the whole osteogenesis process. More importantly, the co-existence of mixed-valent vanadium species was able to continuously stimulate the generation of excessive ROS and the depletion of GSH by synergistically supplying an appropriate ratio of V(IV) and V(V) to thermodynamically and kinetically maintain the stable self-circulation of the valence state alteration, thus inducing UMR-106 cell death. In a rat model, V(IV/V)-MBG/PLGA scaffolds effectively suppressed tumor invasion and promoted bone regeneration. These results suggest that V(IV/V)-MBG/PLGA scaffolds are a promising strategy for treating tumor-associated bone defects, offering dual tumor inhibition and bone regeneration.
{"title":"Mixed-valence vanadium-doped mesoporous bioactive glass for treatment of tumor-associated bone defects.","authors":"Xin Liu, Peng Zhang, Mengjie Xu, Zihao Zhao, Xing Yin, Ximing Pu, Juan Wang, Xiaoming Liao, Zhongbing Huang, Shunze Cao, Guangfu Yin","doi":"10.1039/d4tb02290d","DOIUrl":"https://doi.org/10.1039/d4tb02290d","url":null,"abstract":"<p><p>Vanadium is a bioactive trace element with variable valence. Its pentavalent form has been confirmed to be capable of predominantly regulating the early and mid-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without tumor inhibition, while its tetravalent form exhibits tumor inhibition but only primarily modulates late osteogenic differentiation and angiogenesis. In this study, a multifunctional bone tissue scaffold consisting of mixed-valence vanadium-doped mesoporous bioactive glass and poly(lactic-<i>co</i>-glycolic acid) (V(IV/V)-MBG/PLGA) was developed to simultaneously inhibit the recurrence of osteosarcoma and promote the regeneration of operative bone defects. The <i>in vitro</i> results showed that the V(IV) and V(V) species could be sustainably released from V(IV/V)-MBG and complementarily enhance the proliferation, osteogenic differentiation, and mineralization of BMSCs by activating multiple signaling pathways throughout the whole osteogenesis process. More importantly, the co-existence of mixed-valent vanadium species was able to continuously stimulate the generation of excessive ROS and the depletion of GSH by synergistically supplying an appropriate ratio of V(IV) and V(V) to thermodynamically and kinetically maintain the stable self-circulation of the valence state alteration, thus inducing UMR-106 cell death. In a rat model, V(IV/V)-MBG/PLGA scaffolds effectively suppressed tumor invasion and promoted bone regeneration. These results suggest that V(IV/V)-MBG/PLGA scaffolds are a promising strategy for treating tumor-associated bone defects, offering dual tumor inhibition and bone regeneration.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}