Alexandra Machado, Miguel Gama, José Alberto Martins
In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.
{"title":"Development of a dextrin-vitamin D3 micelle nanocarrier for the antimicrobial peptide LLKKK18 as a potential therapeutic agent for bone infections.","authors":"Alexandra Machado, Miguel Gama, José Alberto Martins","doi":"10.1039/d4tb00903g","DOIUrl":"10.1039/d4tb00903g","url":null,"abstract":"<p><p>In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against <i>S. aureus</i>, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402513","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}
Erdem Şahin, Roberta Ruggiero, Marco Tatullo, Francesco Paduano, Meltem Alp, Ahmed Şeref
Background: Magnesium alloys degrade rapidly in salt solutions, which limits their use without passivating treatments. AZ31 alloy is particularly promising for implant applications owing to its biodegradability and mechanical properties, necessitating effective corrosion-resistant coatings. Aim: In this study, a self-passivating reactive coating was designed and evaluated for AZ31 magnesium alloy plates using β-tricalcium phosphate (TCP) to enhance corrosion resistance and biocompatibility. Methods: Solutions of TCP, trisodium citrate, magnesium nitrate, hydroxyethyl cellulose (HEC), and sodium chloride were used to dip-coat AZ31 plates. The coated samples were immersed in 3.5 wt% NaCl solution. Phase evolution was analysed using gravimetry, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). The biological response of the coated samples was evaluated through MTT and resazurin assays. Results: The coating formed a stable TCP/HEC layer that gradually dissolved over two weeks, converting the surface to magnesium hydroxide, magnesium oxychloride, and magnesium phosphate phases. The formation of brucite, responsible for passivation in the long term, was observed. The coating effectively prevented excessive magnesium oxychloride formation and stabilised magnesium hydroxide after one week. Biological characterization indicated that the coating on AZ31 is safe on the Saos-2 and L929 cell lines. Conclusion: The TCP-based coating enhances the corrosion resistance of AZ31 alloy in salt solutions, promoting passivating phases and limiting corrosive products, thereby ameliorating biocompatibility issues. This coating demonstrates substantial potential for extending the longevity and functionality of magnesium alloy implants.
{"title":"Design and characterization of β-tricalcium phosphate-based self-passivating coatings on magnesium alloys.","authors":"Erdem Şahin, Roberta Ruggiero, Marco Tatullo, Francesco Paduano, Meltem Alp, Ahmed Şeref","doi":"10.1039/d4tb01214c","DOIUrl":"10.1039/d4tb01214c","url":null,"abstract":"<p><p><i>Background</i>: Magnesium alloys degrade rapidly in salt solutions, which limits their use without passivating treatments. AZ31 alloy is particularly promising for implant applications owing to its biodegradability and mechanical properties, necessitating effective corrosion-resistant coatings. <i>Aim</i>: In this study, a self-passivating reactive coating was designed and evaluated for AZ31 magnesium alloy plates using β-tricalcium phosphate (TCP) to enhance corrosion resistance and biocompatibility. <i>Methods</i>: Solutions of TCP, trisodium citrate, magnesium nitrate, hydroxyethyl cellulose (HEC), and sodium chloride were used to dip-coat AZ31 plates. The coated samples were immersed in 3.5 wt% NaCl solution. Phase evolution was analysed using gravimetry, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). The biological response of the coated samples was evaluated through MTT and resazurin assays. <i>Results</i>: The coating formed a stable TCP/HEC layer that gradually dissolved over two weeks, converting the surface to magnesium hydroxide, magnesium oxychloride, and magnesium phosphate phases. The formation of brucite, responsible for passivation in the long term, was observed. The coating effectively prevented excessive magnesium oxychloride formation and stabilised magnesium hydroxide after one week. Biological characterization indicated that the coating on AZ31 is safe on the Saos-2 and L929 cell lines. <i>Conclusion</i>: The TCP-based coating enhances the corrosion resistance of AZ31 alloy in salt solutions, promoting passivating phases and limiting corrosive products, thereby ameliorating biocompatibility issues. This coating demonstrates substantial potential for extending the longevity and functionality of magnesium alloy implants.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484341","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}
The ionic environment has a strong influence on the bioelectricity of skin, which is also present in the wound healing process. Inspired by this, we proposed a mechanism for hydrogel-based dressings to respond to endogenous electric fields through exudate absorption and conducted a verification study using a typical hydrogel, namely, polyacrylamide and sodium alginate (PAM-SA) hydrogels, as an example. Theoretical calculations showed that the PAM-SA hydrogels could absorb and orient the various electrolytes of exudate in the hydrogel at the wound site, contributing to the reconstruction of the electric field at the wound site. During the treatment process, this effect significantly accelerated the healing process of the rat epidermis, which exceeded the conventional dressing in terms of healing speed and efficacy, and the wounds on the complete layer of rat skin (wound area: 1.13 cm2) could be rapidly repaired within 10 days. Revealing the electrophysiological behavior of PAM-SA dressings during wound healing can help further improve the design model, the optimization concept, and development paths for the bioelectrical structures of modern dressings and bioelectrical stimulation in wound healing.
{"title":"Reconfiguring the endogenous electric field of a wound through a conductive hydrogel for effective exudate management to enhance skin wound healing.","authors":"Yukun Yan, Yuanyuan Chen, Hanqing Dai, Wanlu Zhang, Ruiqian Guo","doi":"10.1039/d4tb01349b","DOIUrl":"10.1039/d4tb01349b","url":null,"abstract":"<p><p>The ionic environment has a strong influence on the bioelectricity of skin, which is also present in the wound healing process. Inspired by this, we proposed a mechanism for hydrogel-based dressings to respond to endogenous electric fields through exudate absorption and conducted a verification study using a typical hydrogel, namely, polyacrylamide and sodium alginate (PAM-SA) hydrogels, as an example. Theoretical calculations showed that the PAM-SA hydrogels could absorb and orient the various electrolytes of exudate in the hydrogel at the wound site, contributing to the reconstruction of the electric field at the wound site. During the treatment process, this effect significantly accelerated the healing process of the rat epidermis, which exceeded the conventional dressing in terms of healing speed and efficacy, and the wounds on the complete layer of rat skin (wound area: 1.13 cm<sup>2</sup>) could be rapidly repaired within 10 days. Revealing the electrophysiological behavior of PAM-SA dressings during wound healing can help further improve the design model, the optimization concept, and development paths for the bioelectrical structures of modern dressings and bioelectrical stimulation in wound healing.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583720","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}
Tianjing Bao, Jian Ren, Yiyuan Wu, Yang Cao, Haobo Pan, Chunlin Deng
The repair of bone defects caused by osteosarcoma is still a significant clinical issue, and new scaffolds need to be developed to solve this problem. The ocean is a treasure trove for developing new biomedical materials, and coral is widely thought to be suitable as a scaffold for bone implant materials due to its porous structure and mechanical properties. Selenium is known for its antioxidant and antitumor effects, inducing tumor cell cycle arrest. In this study, we hydrothermally transformed corals to grow a hydroxyapatite layer on the scaffold surface (CHAp) and combined it with selenium to obtain selenium-doped scaffolds (Se-CHAp) without affecting the porous structure of the coral. The research successfully validates their biocompatibility and the antitumor efficacy against 143B osteosarcoma cells. The results indicate that the Se-CHAp scaffolds yielded an obvious inhibitory effect on the proliferation of osteosarcoma cells, highlighting that they have huge prospects for application in biomedical technology.
{"title":"Study on porous coral scaffolds containing a hydroxyapatite layer doped with selenium and their properties.","authors":"Tianjing Bao, Jian Ren, Yiyuan Wu, Yang Cao, Haobo Pan, Chunlin Deng","doi":"10.1039/d4tb01112k","DOIUrl":"10.1039/d4tb01112k","url":null,"abstract":"<p><p>The repair of bone defects caused by osteosarcoma is still a significant clinical issue, and new scaffolds need to be developed to solve this problem. The ocean is a treasure trove for developing new biomedical materials, and coral is widely thought to be suitable as a scaffold for bone implant materials due to its porous structure and mechanical properties. Selenium is known for its antioxidant and antitumor effects, inducing tumor cell cycle arrest. In this study, we hydrothermally transformed corals to grow a hydroxyapatite layer on the scaffold surface (CHAp) and combined it with selenium to obtain selenium-doped scaffolds (Se-CHAp) without affecting the porous structure of the coral. The research successfully validates their biocompatibility and the antitumor efficacy against 143B osteosarcoma cells. The results indicate that the Se-CHAp scaffolds yielded an obvious inhibitory effect on the proliferation of osteosarcoma cells, highlighting that they have huge prospects for application in biomedical technology.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484362","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}
The aggregation of amyloid β peptide (Aβ) in the presence of elevated levels of transition-metal ions, e.g., Fe3+, Cu2+, Zn2+, is accountable for enhanced cellular toxicity in Alzheimer's disease. Many strategies are reported to inhibit either Cu2+, Zn2+, or Fe3+-induced Aβ fibrillation, focused on one metal. Herein, a taurine-containing adaptable metal sequestering peptide (AMSP) has been developed as the modulator of any of the cited metal-induced Aβ-aggregation in vitro. We designed the peptide conjugate comprising VFFA as a recognition motif and a taurine moiety coupled with a pendant chain of glutamic acid such that the -SO3H groups of taurine lie nearby 13His and 14His of Aβ, and sequester such metal ions that construct the salt bridge preponderantly via13His-metal-14His composition as well as bridges with 6His of Aβ. We checked the modulation of fibrillar aggregates of Aβ in the presence of metal ions by monitoring the fibril accumulation using several biophysical methods. The results established that non-aggregating AMSP sequesters Zn2+ preferably, along with Fe3+ and Cu2+ ions from the metal-Aβ complex at the physiological condition, efficiently inhibiting Aβ aggregation. While such adaptable metal binders that can chelate various metals are new, AMSP inhibits aggregation through selective recognition and metal scavenging.
{"title":"A smart adaptable metal sequestering peptide conjugate to modulate Aβ fibrillar aggregation.","authors":"Tanmay Mondal, Sujan Kalita, Rinku Dutta, Bhubaneswar Mandal","doi":"10.1039/d4tb01093k","DOIUrl":"10.1039/d4tb01093k","url":null,"abstract":"<p><p>The aggregation of amyloid β peptide (Aβ) in the presence of elevated levels of transition-metal ions, <i>e.g.</i>, Fe<sup>3+</sup>, Cu<sup>2+</sup>, Zn<sup>2+</sup>, is accountable for enhanced cellular toxicity in Alzheimer's disease. Many strategies are reported to inhibit either Cu<sup>2+</sup>, Zn<sup>2+</sup>, or Fe<sup>3+</sup>-induced Aβ fibrillation, focused on one metal. Herein, a taurine-containing adaptable metal sequestering peptide (AMSP) has been developed as the modulator of any of the cited metal-induced Aβ-aggregation <i>in vitro</i>. We designed the peptide conjugate comprising VFFA as a recognition motif and a taurine moiety coupled with a pendant chain of glutamic acid such that the -SO<sub>3</sub>H groups of taurine lie nearby <sup>13</sup>His and <sup>14</sup>His of Aβ, and sequester such metal ions that construct the salt bridge preponderantly <i>via</i><sup>13</sup>His-metal-<sup>14</sup>His composition as well as bridges with <sup>6</sup>His of Aβ. We checked the modulation of fibrillar aggregates of Aβ in the presence of metal ions by monitoring the fibril accumulation using several biophysical methods. The results established that non-aggregating AMSP sequesters Zn<sup>2+</sup> preferably, along with Fe<sup>3+</sup> and Cu<sup>2+</sup> ions from the metal-Aβ complex at the physiological condition, efficiently inhibiting Aβ aggregation. While such adaptable metal binders that can chelate various metals are new, AMSP inhibits aggregation through selective recognition and metal scavenging.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396354","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}
Aleksey A Gagarin, Artem S Minin, Vadim A Shevyrin, Enrico Benassi, Nataliya P Belskaya
A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids-MPTA and peptides-MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure.
{"title":"Photocaging of amino acids and short peptides by arylidenethiazoles: mechanism, photochemical characteristics and biological behaviour.","authors":"Aleksey A Gagarin, Artem S Minin, Vadim A Shevyrin, Enrico Benassi, Nataliya P Belskaya","doi":"10.1039/d4tb01441c","DOIUrl":"10.1039/d4tb01441c","url":null,"abstract":"<p><p>A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids-MPTA and peptides-MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396373","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}
Lei Bai, Wenhui Yi, Taiyang Sun, Yilong Tian, Ping Zhang, Jinhai Si, Xun Hou, Jin Hou
Expression of concern for 'Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer' by Lei Bai et al., J. Mater. Chem. B, 2020, 8, 6402-6417, https://doi.org/10.1039/D0TB01084G.
对 Lei Bai 等人的 "Surface Modification Engineering of Two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer"(《二维碳化钛的表面修饰工程用于乳腺癌的高效协同多疗法》)表示关注,J. Mater.Chem.B,2020,8,6402-6417,https://doi.org/10.1039/D0TB01084G。
{"title":"Expression of concern: Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer.","authors":"Lei Bai, Wenhui Yi, Taiyang Sun, Yilong Tian, Ping Zhang, Jinhai Si, Xun Hou, Jin Hou","doi":"10.1039/d4tb90175d","DOIUrl":"10.1039/d4tb90175d","url":null,"abstract":"<p><p>Expression of concern for 'Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer' by Lei Bai <i>et al.</i>, <i>J. Mater. Chem. B</i>, 2020, <b>8</b>, 6402-6417, https://doi.org/10.1039/D0TB01084G.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549780","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}
Wei-Qun Deng, Jun-Tao Chen, Si-Si Chen, Zhi-Qing Wang, Guo-Jiang Mao, Liufang Hu, Juan Ouyang, Chun-Yan Li
Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.
{"title":"ATP-responsive copper(II)-doped ZIF-nanoparticles for synergistic cancer therapy: combining cuproptosis and chemo/chemodynamic therapy.","authors":"Wei-Qun Deng, Jun-Tao Chen, Si-Si Chen, Zhi-Qing Wang, Guo-Jiang Mao, Liufang Hu, Juan Ouyang, Chun-Yan Li","doi":"10.1039/d4tb01574f","DOIUrl":"10.1039/d4tb01574f","url":null,"abstract":"<p><p>Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu<sup>2+</sup>-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu<sup>2+</sup>-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H<sub>2</sub>O<sub>2</sub> to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. <i>In vivo</i> experimental findings demonstrate that Cu<sup>2+</sup>-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396356","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}
Jiabao Zhuang, Quan Pan, Chunli Zhou, Ziying Cai, Nan Li, Na Zhao
In this work, a series of cationic luminogens (designated as PSMP isomers) were developed based on the cyano positional isomerism strategy. The isomerism of the cyano substituent on the molecular skeleton can finely regulate the optical behaviour, the type of photoinduced reactive oxygen species (ROS), and mitochondria-targeted capability of isomers. Interestingly, PSMP-4, with the cyano group installed at an appropriate location, exhibits a special aggregation-induced emission effect and potent O2˙- generation efficacy through the type I photochemistry pathway. Notably, PSMP-4 can accumulate in mitochondria with high specificity. Taking advantage of its excellent photostability, PSMP-4 realizes in situ mitochondria imaging in a washing-free manner and sensitive response to the change of mitochondrial membrane potential. The integration of comprehensive photophysical properties and mitochondrial specificity enable PSMP-4 to successfully trigger the death of cancer cells through an efficient type I photodynamic therapy process both in vitro and in multicellular tumor spheroid models.
这项研究基于氰基位置异构策略开发了一系列阳离子发光剂(命名为 PSMP 异构体)。分子骨架上氰基取代基的异构可以精细调节异构体的光学行为、光诱导活性氧(ROS)的类型以及线粒体靶向能力。有趣的是,在适当位置加入氰基的 PSMP-4 通过 I 型光化学途径表现出特殊的聚集诱导发射效应和强效的 O2˙-生成功效。值得注意的是,PSMP-4 能以高度特异性积聚在线粒体中。利用其优异的光稳定性,PSMP-4 可以免清洗的方式实现线粒体原位成像,并对线粒体膜电位的变化做出灵敏反应。综合的光物理特性和线粒体特异性使 PSMP-4 能够在体外和多细胞肿瘤球体模型中通过高效的 I 型光动力疗法过程成功引发癌细胞死亡。
{"title":"The cyano positional isomerism strategy for constructing mitochondria-targeted AIEgens with type I reactive oxygen species generation capability.","authors":"Jiabao Zhuang, Quan Pan, Chunli Zhou, Ziying Cai, Nan Li, Na Zhao","doi":"10.1039/d4tb01847h","DOIUrl":"10.1039/d4tb01847h","url":null,"abstract":"<p><p>In this work, a series of cationic luminogens (designated as PSMP isomers) were developed based on the cyano positional isomerism strategy. The isomerism of the cyano substituent on the molecular skeleton can finely regulate the optical behaviour, the type of photoinduced reactive oxygen species (ROS), and mitochondria-targeted capability of isomers. Interestingly, PSMP-4, with the cyano group installed at an appropriate location, exhibits a special aggregation-induced emission effect and potent O<sub>2</sub>˙<sup>-</sup> generation efficacy through the type I photochemistry pathway. Notably, PSMP-4 can accumulate in mitochondria with high specificity. Taking advantage of its excellent photostability, PSMP-4 realizes <i>in situ</i> mitochondria imaging in a washing-free manner and sensitive response to the change of mitochondrial membrane potential. The integration of comprehensive photophysical properties and mitochondrial specificity enable PSMP-4 to successfully trigger the death of cancer cells through an efficient type I photodynamic therapy process both <i>in vitro</i> and in multicellular tumor spheroid models.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484366","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}
Radhakrishnan Sreena, Gurusamy Raman, Geetha Manivasagam, A Joseph Nathanael
Most natural and synthetic polymers are promising materials for biomedical applications because of their biocompatibility, abundant availability, and biodegradability. Their properties can be tailored according to the intended application by fabricating composites with other polymers or ceramics. The incorporation of ceramic nanoparticles such as bioactive glass (BG) and hydroxyapatite aids in the improvement of mechanical and biological characteristics and alters the degradation kinetics of polymers. BG can be used in the form of nanoparticles, nanofibers, scaffolds, pastes, hydrogels, or coatings and is significantly employed in different applications. This biomaterial is highly preferred because of its excellent biocompatibility, bone-stimulating activity, and favourable mechanical and degradation characteristics. Different compositions of nano BG are incorporated into the polymer system and studied for positive results such as enhanced bioactivity, better cell adherence, and proliferation rate. This review summarizes the fabrication and the progress of natural/synthetic polymer-nano BG systems for biomedical applications such as drug delivery, wound healing, and tissue engineering. The challenges and the future perspectives of the composite system are also addressed.
{"title":"Bioactive glass-polymer nanocomposites: a comprehensive review on unveiling their biomedical applications.","authors":"Radhakrishnan Sreena, Gurusamy Raman, Geetha Manivasagam, A Joseph Nathanael","doi":"10.1039/d4tb01525h","DOIUrl":"10.1039/d4tb01525h","url":null,"abstract":"<p><p>Most natural and synthetic polymers are promising materials for biomedical applications because of their biocompatibility, abundant availability, and biodegradability. Their properties can be tailored according to the intended application by fabricating composites with other polymers or ceramics. The incorporation of ceramic nanoparticles such as bioactive glass (BG) and hydroxyapatite aids in the improvement of mechanical and biological characteristics and alters the degradation kinetics of polymers. BG can be used in the form of nanoparticles, nanofibers, scaffolds, pastes, hydrogels, or coatings and is significantly employed in different applications. This biomaterial is highly preferred because of its excellent biocompatibility, bone-stimulating activity, and favourable mechanical and degradation characteristics. Different compositions of nano BG are incorporated into the polymer system and studied for positive results such as enhanced bioactivity, better cell adherence, and proliferation rate. This review summarizes the fabrication and the progress of natural/synthetic polymer-nano BG systems for biomedical applications such as drug delivery, wound healing, and tissue engineering. The challenges and the future perspectives of the composite system are also addressed.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402512","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}