Yi-Jung Sung, Wei-Ting Cai, Yi-Ping Chen, Hardy Wai-Hong Chan, Cong-Kai Lin, Po-Hsiang Wang and Wen-Yih Chen
Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.
{"title":"Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles†","authors":"Yi-Jung Sung, Wei-Ting Cai, Yi-Ping Chen, Hardy Wai-Hong Chan, Cong-Kai Lin, Po-Hsiang Wang and Wen-Yih Chen","doi":"10.1039/D4TB00509K","DOIUrl":"10.1039/D4TB00509K","url":null,"abstract":"<p >Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment <em>via</em> a fine-tuned methylation location.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319384","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}
Jianing Yi, Luyao Liu, Wenjie Gao, Jie Zeng, Yongzhi Chen, E. Pang, Minhuan Lan and Chunzhao Yu
Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has the advantages of spatiotemporal selectivity, non-invasiveness, and negligible drug resistance. Phototherapy has been approved for treating superficial epidermal tumors. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment and the highly expressed heat shock protein. Moreover, poor tissue penetration and focused irradiation laser region in phototherapy make treating deep tissues and metastatic tumors challenging. Combination therapy strategies, which integrate the advantages of each treatment and overcome their disadvantages, can significantly improve the therapeutic efficacy. Recently, many combination therapy strategies have been reported. Our study summarizes the strategies used for combining phototherapy with other cancer treatments such as chemotherapy, immunotherapy, sonodynamic therapy, gas therapy, starvation therapy, and chemodynamic therapy. Some research cases were selected to analyze the combination therapy effect, delivery platform feature, and synergetic anticancer mechanisms. Moreover, additional research cases are summarized in the tables. This review provides strong evidence that phototherapy-based combination strategies can enhance the anticancer effect compared with phototherapy alone. Additionally, the challenges and future perspectives associated with these combinational therapies are discussed.
{"title":"Advances and perspectives in phototherapy-based combination therapy for cancer treatment","authors":"Jianing Yi, Luyao Liu, Wenjie Gao, Jie Zeng, Yongzhi Chen, E. Pang, Minhuan Lan and Chunzhao Yu","doi":"10.1039/D4TB00483C","DOIUrl":"10.1039/D4TB00483C","url":null,"abstract":"<p >Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has the advantages of spatiotemporal selectivity, non-invasiveness, and negligible drug resistance. Phototherapy has been approved for treating superficial epidermal tumors. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment and the highly expressed heat shock protein. Moreover, poor tissue penetration and focused irradiation laser region in phototherapy make treating deep tissues and metastatic tumors challenging. Combination therapy strategies, which integrate the advantages of each treatment and overcome their disadvantages, can significantly improve the therapeutic efficacy. Recently, many combination therapy strategies have been reported. Our study summarizes the strategies used for combining phototherapy with other cancer treatments such as chemotherapy, immunotherapy, sonodynamic therapy, gas therapy, starvation therapy, and chemodynamic therapy. Some research cases were selected to analyze the combination therapy effect, delivery platform feature, and synergetic anticancer mechanisms. Moreover, additional research cases are summarized in the tables. This review provides strong evidence that phototherapy-based combination strategies can enhance the anticancer effect compared with phototherapy alone. Additionally, the challenges and future perspectives associated with these combinational therapies are discussed.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422243","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}
Jia-Hao Bai, Qing-Tao Yu, Yi-Wu Wang, Chun-Fa Chen, Lian-Ju Ma, Yue Yuan, Yong-Jun Gan, Jia-Qi Yang, Shu Zhu, Yu-Hang Ran, Li-Lei Zhang, Hang Qian, Zheng-Huan Zhao and Qian Liu
Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.
自组装 DNA 纳米结构在生物传感、药物传输和纳米医学领域大有可为。然而,DNA 纳米结构在生理条件下的不稳定性和低细胞吸收效率等挑战限制了其实际应用。为了解决这些障碍,本研究提出了一种将阳离子聚合物聚乙烯亚胺(PEI)与 DNA 自组装相结合的新方法。假设带正电荷的线性聚乙烯亚胺能促进 DNA 纳米结构的自组装,保护它们免受恶劣条件的影响,并赋予它们聚乙烯亚胺的细胞渗透特性。实验证明,通过 PEI 介导成功合成了 DNA 纳米管(PNT),与传统的 Mg2+ 组装 DNA 纳米管相比,PNT 的稳定性和细胞吸收效率显著提高。研究进一步发现,在 PEI 和 DNA 的共同作用下,其内吞机制既有凝集素介导的内吞,也有洞穴素介导的内吞。为了展示这种混合纳米结构在生物医学领域的适用性,装载了 KRAS siRNA 的 PNT 被有效地输送到肺腺癌细胞中,在体外产生了良好的抗癌效果。这些研究结果表明,PEI 介导的 DNA 组装可能成为未来生物医学应用的重要工具。
{"title":"Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy†","authors":"Jia-Hao Bai, Qing-Tao Yu, Yi-Wu Wang, Chun-Fa Chen, Lian-Ju Ma, Yue Yuan, Yong-Jun Gan, Jia-Qi Yang, Shu Zhu, Yu-Hang Ran, Li-Lei Zhang, Hang Qian, Zheng-Huan Zhao and Qian Liu","doi":"10.1039/D4TB00791C","DOIUrl":"10.1039/D4TB00791C","url":null,"abstract":"<p >Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg<small><sup>2+</sup></small>-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects <em>in vitro</em>. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302318","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}
Bahareh Haji Ali, Sepideh Khoee, Fariba Mafakheri, Elahe Sadri, Vahid Pirhajati Mahabadi, Mohammad Reza Karimi, Sakine Shirvalilou and Samideh Khoei
Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood–brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA in vivo, shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic Bax gene and a decrease in the anti-apoptotic Bcl-2 gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting.
{"title":"Active targeted delivery of theranostic thermo/pH dual-responsive magnetic Janus nanoparticles functionalized with folic acid/fluorescein ligands for enhanced DOX combination therapy of rat glioblastoma","authors":"Bahareh Haji Ali, Sepideh Khoee, Fariba Mafakheri, Elahe Sadri, Vahid Pirhajati Mahabadi, Mohammad Reza Karimi, Sakine Shirvalilou and Samideh Khoei","doi":"10.1039/D3TB02429F","DOIUrl":"10.1039/D3TB02429F","url":null,"abstract":"<p >Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood–brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA <em>in vivo</em>, shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic <em>Bax</em> gene and a decrease in the anti-apoptotic <em>Bcl-2</em> gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163178","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}
Li Xia, Cheng Ni, Huxiao Sun, Honghua Guo, Haoyu Huang, Xueyan Cao, Jindong Xia, Xiangyang Shi and Rui Guo
The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)–iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo–chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.5 nm, which could accumulate at tumor sites after circulation and be specifically taken up by metastatic 4T1 cells overexpressing CD44 receptors. In the tumor microenvironment, TFP@ATO-HA could release ATO/cisplatin and Fe3+ in a pH-responsive manner, deplete glutathione, and generate reactive oxygen species with endogenous H2O2 for chemodynamic therapy (CDT). Additionally, ATO could enhance chemotherapeutic efficacy by inhibiting mitochondrial respiration, relieving hypoxia, and amplifying the CDT effect by decreasing intracellular pH and elevating Fenton reaction efficiency. In vivo experiments demonstrated that TFP@ATO-HA could effectively inhibit tumor growth and suppress lung metastases without obvious systemic toxicity. Furthermore, TFP@ATO-HA exhibited a r1 relaxivity of 2.6 mM−1 s−1 and targeted MR imaging of 4T1 tumors. Dual drug-loaded metal–phenolic networks can be easily prepared and act as effective theranostic nanoplatforms for targeted MR imaging and synergistic chemo–chemodynamic therapy.
{"title":"Dual drug-loaded metal–phenolic networks for targeted magnetic resonance imaging and synergistic chemo–chemodynamic therapy of breast cancer†","authors":"Li Xia, Cheng Ni, Huxiao Sun, Honghua Guo, Haoyu Huang, Xueyan Cao, Jindong Xia, Xiangyang Shi and Rui Guo","doi":"10.1039/D4TB00462K","DOIUrl":"10.1039/D4TB00462K","url":null,"abstract":"<p >The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)–iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo–chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.5 nm, which could accumulate at tumor sites after circulation and be specifically taken up by metastatic 4T1 cells overexpressing CD44 receptors. In the tumor microenvironment, TFP@ATO-HA could release ATO/cisplatin and Fe<small><sup>3+</sup></small> in a pH-responsive manner, deplete glutathione, and generate reactive oxygen species with endogenous H<small><sub>2</sub></small>O<small><sub>2</sub></small> for chemodynamic therapy (CDT). Additionally, ATO could enhance chemotherapeutic efficacy by inhibiting mitochondrial respiration, relieving hypoxia, and amplifying the CDT effect by decreasing intracellular pH and elevating Fenton reaction efficiency. <em>In vivo</em> experiments demonstrated that TFP@ATO-HA could effectively inhibit tumor growth and suppress lung metastases without obvious systemic toxicity. Furthermore, TFP@ATO-HA exhibited a <em>r</em><small><sub>1</sub></small> relaxivity of 2.6 mM<small><sup>−1</sup></small> s<small><sup>−1</sup></small> and targeted MR imaging of 4T1 tumors. Dual drug-loaded metal–phenolic networks can be easily prepared and act as effective theranostic nanoplatforms for targeted MR imaging and synergistic chemo–chemodynamic therapy.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312545","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}
Yue Li, Rong Chang, Yang-Jia Liu, Feng Chen and Yong-Xiang Chen
The regeneration of demineralized enamel holds great significance in the treatment of dental caries. Amelogenin (Ame), an essential protein for mediating natural enamel growth, is no longer secreted after enamel has fully matured in childhood. Although biomimetic mineralization based on peptides or proteins has made significant progress, easily accessible, low-cost, biocompatible and highly effective Ame mimics are still lacking. Herein, we construct a series of amphiphilic branched polypeptides (CAMPs) by facile coupling of the Ame's C-terminal segment and poly(γ-benzyl-L-glutamate), which serves to simulate the Ame's hydrophobic N-terminal segment. Among them, CAMP15 is the best biomimetic mineralization template with great self-assembly performance to guide the oriented crystallization of hydroxyapatite and is capable of inhibiting the adhesion of Streptococcus mutans and Staphylococcus aureus on the enamel surfaces. This work highlights the potential application of amphiphilic branched polypeptide as Ame mimics in repairing defected enamel, providing a promising strategy for prevention and treatment of dental caries.
脱矿釉质的再生对治疗龋齿具有重要意义。釉质素(Ame)是介导釉质自然生长的一种重要蛋白质,在儿童期釉质完全成熟后就不再分泌。尽管基于多肽或蛋白质的生物仿矿化技术已取得重大进展,但目前仍缺乏易于获得、成本低廉、生物相容性好且高效的釉质素模拟物。在本文中,我们通过将 Ame 的 C 端与聚(γ-苄基-L-谷氨酸)轻松偶联,构建了一系列两亲性支链多肽(CAMPs),后者可模拟 Ame 的疏水性 N 端。其中,CAMP15 是最佳的仿生矿化模板,具有良好的自组装性能,可引导羟基磷灰石定向结晶,并能抑制变异链球菌和金黄色葡萄球菌在釉质表面的粘附。这项工作凸显了两亲性支链多肽作为 Ame 模拟物在修复缺损釉质方面的潜在应用,为龋齿的预防和治疗提供了一种前景广阔的策略。
{"title":"Self-assembled branched polypeptides as amelogenin mimics for enamel repair†","authors":"Yue Li, Rong Chang, Yang-Jia Liu, Feng Chen and Yong-Xiang Chen","doi":"10.1039/D3TB02709K","DOIUrl":"10.1039/D3TB02709K","url":null,"abstract":"<p >The regeneration of demineralized enamel holds great significance in the treatment of dental caries. Amelogenin (Ame), an essential protein for mediating natural enamel growth, is no longer secreted after enamel has fully matured in childhood. Although biomimetic mineralization based on peptides or proteins has made significant progress, easily accessible, low-cost, biocompatible and highly effective Ame mimics are still lacking. Herein, we construct a series of amphiphilic branched polypeptides (CAMPs) by facile coupling of the Ame's C-terminal segment and poly(γ-benzyl-<small>L</small>-glutamate), which serves to simulate the Ame's hydrophobic N-terminal segment. Among them, CAMP<small><sub>15</sub></small> is the best biomimetic mineralization template with great self-assembly performance to guide the oriented crystallization of hydroxyapatite and is capable of inhibiting the adhesion of <em>Streptococcus mutans</em> and <em>Staphylococcus aureus</em> on the enamel surfaces. This work highlights the potential application of amphiphilic branched polypeptide as Ame mimics in repairing defected enamel, providing a promising strategy for prevention and treatment of dental caries.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302320","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}
Periodontitis is an immune-inflammatory disease caused by dental plaque, and deteriorates the periodontal ligament, causes alveolar bone loss, and may lead to tooth loss. To treat periodontitis, antibacterial and anti-inflammation approaches are required to reduce bone loss. Thus, appropriate drug administration methods are significant. Due to their “syringeability”, biocompatibility, and convenience, injectable hydrogels and associated methods have been extensively studied and used for periodontitis therapy. Such hydrogels are made from natural and synthetic polymer materials using physical and/or chemical cross-linking approaches. Interestingly, some injectable hydrogels are stimuli-responsive hydrogels, which respond to the local microenvironment and form hydrogels that release drugs. Therefore, as injectable hydrogels are different and highly varied, we systematically reviewed the periodontal treatment field from three perspectives: raw material sources, cross-linking methods, and stimuli-responsive methods. We then discussed current challenges and opportunities for the translation of hydrogels to clinic, which may guide further injectable hydrogel designs for periodontitis.
{"title":"Recent advances in injectable hydrogel therapies for periodontitis","authors":"Shidian Ran, Linyu Xue, Xiaorui Wei, Jindie Huang, Xingrui Yan, Tong-Chuan He, Zhurong Tang, Hongmei Zhang and Mengqin Gu","doi":"10.1039/D3TB03070A","DOIUrl":"10.1039/D3TB03070A","url":null,"abstract":"<p >Periodontitis is an immune-inflammatory disease caused by dental plaque, and deteriorates the periodontal ligament, causes alveolar bone loss, and may lead to tooth loss. To treat periodontitis, antibacterial and anti-inflammation approaches are required to reduce bone loss. Thus, appropriate drug administration methods are significant. Due to their “syringeability”, biocompatibility, and convenience, injectable hydrogels and associated methods have been extensively studied and used for periodontitis therapy. Such hydrogels are made from natural and synthetic polymer materials using physical and/or chemical cross-linking approaches. Interestingly, some injectable hydrogels are stimuli-responsive hydrogels, which respond to the local microenvironment and form hydrogels that release drugs. Therefore, as injectable hydrogels are different and highly varied, we systematically reviewed the periodontal treatment field from three perspectives: raw material sources, cross-linking methods, and stimuli-responsive methods. We then discussed current challenges and opportunities for the translation of hydrogels to clinic, which may guide further injectable hydrogel designs for periodontitis.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312546","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}
Elisabetta Rosa, Enza Di Gregorio, Giuseppe Ferrauto, Carlo Diaferia, Enrico Gallo, Enzo Terreno and Antonella Accardo
The self-assembly of peptides and peptide analogues may be exploited to develop platforms for different biomedical applications, among which CEST-MRI (chemical exchange saturation transfer magnetic resonance imaging) represents one of the most attractive techniques to be explored as a novel metal-free contrast approach in imaging acquisitions. A lysine-containing peptide sequence (LIVAGK-NH2, named K2) was thus modified by insertion, at the N-terminus, of a peptide nucleic acid (PNA) base, leading to a primary amine suitable for the signal generation. a-K2, c-K2, g-K2 and t-K2 peptides were synthesized and characterized. The c-K2 sequence displayed gelling properties and the Watson and Crick pairing, arising from its combination with g-K2, allowed a significant increase in the mechanical responsivity of the hydrogel. These matrices were able to generate a CEST signal around 2.5 ppm from water and, after assessing their cytocompatibility on GL261 (murine glioma), TS/a (murine breast carcinoma), and 3T3-NIH (murine fibroblasts) cell lines, their capability to work as implants for in vivo detection, was proved by intratumor injection in Balb/c mice inoculated with TS/a murine breast cancer cells.
{"title":"Hybrid PNA-peptide hydrogels as injectable CEST-MRI agents†","authors":"Elisabetta Rosa, Enza Di Gregorio, Giuseppe Ferrauto, Carlo Diaferia, Enrico Gallo, Enzo Terreno and Antonella Accardo","doi":"10.1039/D4TB00358F","DOIUrl":"10.1039/D4TB00358F","url":null,"abstract":"<p >The self-assembly of peptides and peptide analogues may be exploited to develop platforms for different biomedical applications, among which CEST-MRI (chemical exchange saturation transfer magnetic resonance imaging) represents one of the most attractive techniques to be explored as a novel metal-free contrast approach in imaging acquisitions. A lysine-containing peptide sequence (LIVAGK-NH<small><sub>2</sub></small>, named K2) was thus modified by insertion, at the N-terminus, of a peptide nucleic acid (PNA) base, leading to a primary amine suitable for the signal generation. a-K2, c-K2, g-K2 and t-K2 peptides were synthesized and characterized. The c-K2 sequence displayed gelling properties and the Watson and Crick pairing, arising from its combination with g-K2, allowed a significant increase in the mechanical responsivity of the hydrogel. These matrices were able to generate a CEST signal around 2.5 ppm from water and, after assessing their cytocompatibility on GL261 (murine glioma), TS/a (murine breast carcinoma), and 3T3-NIH (murine fibroblasts) cell lines, their capability to work as implants for <em>in vivo</em> detection, was proved by intratumor injection in Balb/c mice inoculated with TS/a murine breast cancer cells.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00358f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino acids show promise as versatile biomolecules for creating a variety of functional biomaterials. Previously, we discovered a novel amino acid reaction, in which a single amino acid can form browning species in a simple solvent mixture comprising DMSO and acetone at room temperature. In the present study, we initially conducted a comprehensive analysis of 190 pairs of binary amino acids (i.e., all the possible pairwise combinations out of 20 amino acids) and identified several surprising combinations that exhibited synergistic browning effects. Particularly, cysteine–lysine and cysteine–arginine pairs exhibited pronounced browning in DMSO/acetone cosolvent solutions. We hypothesize that the coloured species result from the formation of extended, hydrophobic molecules with highly conjugated systems, arising from extensive condensation reactions between amino acids. Subsequently, we aimed at developing a nano-platform based on this newly discovered amino acid reaction. We demonstrate that through a nanoprecipitation process (solvent-shifting), spherical nanoparticles with sizes ranging from 100 to 200 nm can be produced, in the presence of ferric ions added to the water phase. Through systematic optimization and comprehensive characterization, the final product is a zwitterionic, charge-reversible nanoparticle featuring three functional groups on its surface: carboxylates, amines, and thiols. Furthermore, it possesses mild antioxidant activity, making it a new type of nano-antioxidant. Finally, we present preliminary results highlighting the potential of using this new nanomaterial as a delivery system for polynucleotides. In conclusion, the paper introduces a novel class of amino acid-derived nanoparticles with significant promise for future biomedical applications.
{"title":"A nano-platform harnessing synergistic amino acid browning for biomedical applications†","authors":"Teh-Min Hu, Jia-An Liang and Yi-Hua Chiang","doi":"10.1039/D4TB00529E","DOIUrl":"10.1039/D4TB00529E","url":null,"abstract":"<p >Amino acids show promise as versatile biomolecules for creating a variety of functional biomaterials. Previously, we discovered a novel amino acid reaction, in which a single amino acid can form browning species in a simple solvent mixture comprising DMSO and acetone at room temperature. In the present study, we initially conducted a comprehensive analysis of 190 pairs of binary amino acids (<em>i.e.</em>, all the possible pairwise combinations out of 20 amino acids) and identified several surprising combinations that exhibited synergistic browning effects. Particularly, cysteine–lysine and cysteine–arginine pairs exhibited pronounced browning in DMSO/acetone cosolvent solutions. We hypothesize that the coloured species result from the formation of extended, hydrophobic molecules with highly conjugated systems, arising from extensive condensation reactions between amino acids. Subsequently, we aimed at developing a nano-platform based on this newly discovered amino acid reaction. We demonstrate that through a nanoprecipitation process (solvent-shifting), spherical nanoparticles with sizes ranging from 100 to 200 nm can be produced, in the presence of ferric ions added to the water phase. Through systematic optimization and comprehensive characterization, the final product is a zwitterionic, charge-reversible nanoparticle featuring three functional groups on its surface: carboxylates, amines, and thiols. Furthermore, it possesses mild antioxidant activity, making it a new type of nano-antioxidant. Finally, we present preliminary results highlighting the potential of using this new nanomaterial as a delivery system for polynucleotides. In conclusion, the paper introduces a novel class of amino acid-derived nanoparticles with significant promise for future biomedical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297618","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}
Manjeet Singh, Mohd Anees, Aiman Afreen, Dinesh Kalyanasundaram, Naresh Bhatnagar and Harpal Singh
Voice prostheses are known to fail in few weeks to several months of implantation due to the clogging mainly caused by microbial biofilm formation, which is a cause of concern. Iodine is a known broad-spectrum biocide and is reported to easily form complexes with various polymers. For long term device disinfection, strong iodine complexation that offers sustained iodine release for a prolonged period is essential. The present research work deals with the synthesis of a poly(methyl methacrylate-n-butyl acrylate-N-vinyl-2-pyrrolidone) (poly[MMA-BA-NVP]) tercopolymer through free radical polymerization for surface coating thermoplastic polyurethane (TPU) based voice prostheses. The NVP content in the tercopolymer was varied from 20% to 50% to optimise iodine loading and subsequent release. Base TPU coated with the tercopolymer was treated with 4% aqueous iodine solution at room temperature (28 ± 3 °C) for two hours. It was observed that the tercopolymer containing 35% N-vinyl-2-pyrrolidone (NVP), 32.5% methyl methacrylate (MMA) and 32.5% butyl acrylate (nBA) gave a stable coating on TPUs together with sustained iodine release for a prolonged period. Furthermore, the tercopolymer coated and iodine loaded TPUs exhibited excellent antimicrobial activity against Candida albicans, Staphylococcus aureus and Escherichia coli.
{"title":"Development of iodine based sustained release antimicrobial coatings for polyurethane voice prostheses†","authors":"Manjeet Singh, Mohd Anees, Aiman Afreen, Dinesh Kalyanasundaram, Naresh Bhatnagar and Harpal Singh","doi":"10.1039/D4TB00439F","DOIUrl":"10.1039/D4TB00439F","url":null,"abstract":"<p >Voice prostheses are known to fail in few weeks to several months of implantation due to the clogging mainly caused by microbial biofilm formation, which is a cause of concern. Iodine is a known broad-spectrum biocide and is reported to easily form complexes with various polymers. For long term device disinfection, strong iodine complexation that offers sustained iodine release for a prolonged period is essential. The present research work deals with the synthesis of a poly(methyl methacrylate-<em>n</em>-butyl acrylate-<em>N</em>-vinyl-2-pyrrolidone) (poly[MMA-BA-NVP]) tercopolymer through free radical polymerization for surface coating thermoplastic polyurethane (TPU) based voice prostheses. The NVP content in the tercopolymer was varied from 20% to 50% to optimise iodine loading and subsequent release. Base TPU coated with the tercopolymer was treated with 4% aqueous iodine solution at room temperature (28 ± 3 °C) for two hours. It was observed that the tercopolymer containing 35% <em>N</em>-vinyl-2-pyrrolidone (NVP), 32.5% methyl methacrylate (MMA) and 32.5% butyl acrylate (<em>n</em>BA) gave a stable coating on TPUs together with sustained iodine release for a prolonged period. Furthermore, the tercopolymer coated and iodine loaded TPUs exhibited excellent antimicrobial activity against <em>Candida albicans</em>, <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159347","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}