Pub Date : 2023-07-13DOI: 10.1186/s40824-023-00413-7
Anoop Puthiyoth Dayanandan, Woong Jin Cho, Hyemin Kang, Alvin Bacero Bello, Byoung Ju Kim, Yoshie Arai, Soo-Hong Lee
Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.
{"title":"Emerging nano-scale delivery systems for the treatment of osteoporosis.","authors":"Anoop Puthiyoth Dayanandan, Woong Jin Cho, Hyemin Kang, Alvin Bacero Bello, Byoung Ju Kim, Yoshie Arai, Soo-Hong Lee","doi":"10.1186/s40824-023-00413-7","DOIUrl":"10.1186/s40824-023-00413-7","url":null,"abstract":"<p><p>Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"68"},"PeriodicalIF":11.3,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.1186/s40824-023-00382-x
Sangbae Park, Yonghyun Gwon, Shahidul Ahmed Khan, Kyoung-Je Jang, Jangho Kim
Personalized medicine aims to provide tailored medical treatment that considers the clinical, genetic, and environmental characteristics of patients. iPSCs have attracted considerable attention in the field of personalized medicine; however, the inherent limitations of iPSCs prevent their widespread use in clinical applications. That is, it would be important to develop notable engineering strategies to overcome the current limitations of iPSCs. Such engineering approaches could lead to significant advances in iPSC-based personalized therapy by offering innovative solutions to existing challenges, from iPSC preparation to clinical applications. In this review, we summarize how engineering strategies have been used to advance iPSC-based personalized medicine by categorizing the development process into three distinctive steps: 1) the production of therapeutic iPSCs; 2) engineering of therapeutic iPSCs; and 3) clinical applications of engineered iPSCs. Specifically, we focus on engineering strategies and their implications for each step in the development of iPSC-based personalized medicine.
{"title":"Engineering considerations of iPSC-based personalized medicine.","authors":"Sangbae Park, Yonghyun Gwon, Shahidul Ahmed Khan, Kyoung-Je Jang, Jangho Kim","doi":"10.1186/s40824-023-00382-x","DOIUrl":"https://doi.org/10.1186/s40824-023-00382-x","url":null,"abstract":"<p><p>Personalized medicine aims to provide tailored medical treatment that considers the clinical, genetic, and environmental characteristics of patients. iPSCs have attracted considerable attention in the field of personalized medicine; however, the inherent limitations of iPSCs prevent their widespread use in clinical applications. That is, it would be important to develop notable engineering strategies to overcome the current limitations of iPSCs. Such engineering approaches could lead to significant advances in iPSC-based personalized therapy by offering innovative solutions to existing challenges, from iPSC preparation to clinical applications. In this review, we summarize how engineering strategies have been used to advance iPSC-based personalized medicine by categorizing the development process into three distinctive steps: 1) the production of therapeutic iPSCs; 2) engineering of therapeutic iPSCs; and 3) clinical applications of engineered iPSCs. Specifically, we focus on engineering strategies and their implications for each step in the development of iPSC-based personalized medicine.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"67"},"PeriodicalIF":11.3,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9810912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.
Methods: The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.
Results: The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.
{"title":"Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion.","authors":"Yi-Ju Ho, Hsiang-Lung Cheng, Lun-De Liao, Yu-Chun Lin, Hong-Chieh Tsai, Chih-Kuang Yeh","doi":"10.1186/s40824-023-00400-y","DOIUrl":"https://doi.org/10.1186/s40824-023-00400-y","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.</p><p><strong>Methods: </strong>The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO<sub>2</sub>), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.</p><p><strong>Results: </strong>The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO<sub>2</sub> level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"65"},"PeriodicalIF":11.3,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-06DOI: 10.1186/s40824-023-00409-3
Fan Zheng, Yeshuo Ma, Jipeng Ding, Shuai Huang, Shengwang Zhang, Xueyan Huang, Bin Feng, Hongliang Zeng, Fei Chen, Wenbin Zeng
Background: Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy.
Methods: Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury.
Results: We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event.
Conclusions: In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.
背景:自噬是一种重要的自食途径,参与许多生理和病理过程。功能失调细胞器和入侵微生物的溶酶体降解是自噬机制的核心,也是对抗疾病相关病症的必要条件。因此,监测溶酶体微环境的波动对于跟踪自噬的动态过程至关重要。尽管在设计分别测量溶酶体粘度或pH的探针方面已经付出了很多努力,但仍需要验证这两个元素的同时成像,以增强对自噬动态进展的理解。方法:探针HFI分三步合成,用于可视化溶酶体内粘度和pH的变化,实时跟踪自噬。然后进行光谱测定。接下来,应用探针成像细胞在营养剥夺或外部应激下的自噬。此外,采用HFI监测自噬的性能来评估对乙酰氨基酚诱导的肝损伤。结果:我们构建了一个比例双响应探针,HFI,在200 nm范围内具有大的Stokes位移,双波长发射,小背景干扰。HFI的比值荧光信号(R = I 610/I 460)与黏度和pH值均具有良好的相关性。更重要的是,高黏度和低pH值对HFI的发射强度有协同促进作用,使其能够在不干扰固有微环境的情况下特异性地照亮溶酶体。然后,我们成功地利用HFI实时监测饥饿或药物诱导的细胞内自噬。有趣的是,HFI还使我们能够可视化DILI模型肝组织中自噬的发生,以及肝保护药物对这一事件的可逆作用。结论:在这项研究中,我们开发了第一个比例双响应荧光探针HFI,用于实时显示自噬的细节。它可以在对溶酶体固有pH值进行最小扰动的情况下对溶酶体进行成像,使我们能够跟踪活细胞中溶酶体粘度和pH值的变化。最终,HFI具有很大的潜力,可作为复杂生物样品中粘度和pH自噬变化的有用指标,也可用于评估药物安全性。
{"title":"Ratiometric and discriminative visualization of autophagic processes with a novel dual-responded lysosome-specific fluorescent probe.","authors":"Fan Zheng, Yeshuo Ma, Jipeng Ding, Shuai Huang, Shengwang Zhang, Xueyan Huang, Bin Feng, Hongliang Zeng, Fei Chen, Wenbin Zeng","doi":"10.1186/s40824-023-00409-3","DOIUrl":"https://doi.org/10.1186/s40824-023-00409-3","url":null,"abstract":"<p><strong>Background: </strong>Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy.</p><p><strong>Methods: </strong>Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury.</p><p><strong>Results: </strong>We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I <sub>610</sub>/I <sub>460</sub>) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event.</p><p><strong>Conclusions: </strong>In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"66"},"PeriodicalIF":11.3,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-03DOI: 10.1186/s40824-023-00402-w
Xiaolin Xu, Wencai Guan, Xiaolei Yu, Guoxiong Xu, Chenglong Wang
Background: Protocell refers to the basic unit of life and synthetic molecular assembly with cell structure and function. The protocells have great applications in the field of biomedical technology. Simulating the morphology and function of cells is the key to the preparation of protocells. However, some organic solvents used in the preparation process of protocells would damage the function of the bioactive substance. Perfluorocarbon, which has no toxic effect on bioactive substances, is an ideal solvent for protocell preparation. However, perfluorocarbon cannot be emulsified with water because of its inertia.
Methods: Spheroids can be formed in nature even without emulsification, since liquid can reshape the morphology of the solid phase through the scouring action, even if there is no stable interface between the two phases. Inspired by the formation of natural spheroids such as pebbles, we developed non-interfacial self-assembly (NISA) of microdroplets as a step toward synthetic protocells, in which the inert perfluorocarbon was utilized to reshape the hydrogel through the scouring action.
Results: The synthetic protocells were successfully obtained by using NISA-based protocell techniques, with the morphology very similar to native cells. Then we simulated the cell transcription process in the synthetic protocell and used the protocell as an mRNA carrier to transfect 293T cells. The results showed that protocells delivered mRNAs, and successfully expressed proteins in 293T cells. Further, we used the NISA method to fabricate an artificial cell by extracting and reassembling the membrane, proteins, and genomes of ovarian cancer cells. The results showed that the recombination of tumor cells was successfully achieved with similar morphology as tumor cells. In addition, the synthetic protocell prepared by the NISA method was used to reverse cancer chemoresistance by restoring cellular calcium homeostasis, which verified the application value of the synthetic protocell as a drug carrier.
Conclusion: This synthetic protocell fabricated by the NISA method simulates the occurrence and development process of primitive life, which has great potential application value in mRNA vaccine, cancer immunotherapy, and drug delivery.
{"title":"Non-interfacial self-assembly of synthetic protocells.","authors":"Xiaolin Xu, Wencai Guan, Xiaolei Yu, Guoxiong Xu, Chenglong Wang","doi":"10.1186/s40824-023-00402-w","DOIUrl":"10.1186/s40824-023-00402-w","url":null,"abstract":"<p><strong>Background: </strong>Protocell refers to the basic unit of life and synthetic molecular assembly with cell structure and function. The protocells have great applications in the field of biomedical technology. Simulating the morphology and function of cells is the key to the preparation of protocells. However, some organic solvents used in the preparation process of protocells would damage the function of the bioactive substance. Perfluorocarbon, which has no toxic effect on bioactive substances, is an ideal solvent for protocell preparation. However, perfluorocarbon cannot be emulsified with water because of its inertia.</p><p><strong>Methods: </strong>Spheroids can be formed in nature even without emulsification, since liquid can reshape the morphology of the solid phase through the scouring action, even if there is no stable interface between the two phases. Inspired by the formation of natural spheroids such as pebbles, we developed non-interfacial self-assembly (NISA) of microdroplets as a step toward synthetic protocells, in which the inert perfluorocarbon was utilized to reshape the hydrogel through the scouring action.</p><p><strong>Results: </strong>The synthetic protocells were successfully obtained by using NISA-based protocell techniques, with the morphology very similar to native cells. Then we simulated the cell transcription process in the synthetic protocell and used the protocell as an mRNA carrier to transfect 293T cells. The results showed that protocells delivered mRNAs, and successfully expressed proteins in 293T cells. Further, we used the NISA method to fabricate an artificial cell by extracting and reassembling the membrane, proteins, and genomes of ovarian cancer cells. The results showed that the recombination of tumor cells was successfully achieved with similar morphology as tumor cells. In addition, the synthetic protocell prepared by the NISA method was used to reverse cancer chemoresistance by restoring cellular calcium homeostasis, which verified the application value of the synthetic protocell as a drug carrier.</p><p><strong>Conclusion: </strong>This synthetic protocell fabricated by the NISA method simulates the occurrence and development process of primitive life, which has great potential application value in mRNA vaccine, cancer immunotherapy, and drug delivery.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"64"},"PeriodicalIF":11.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells.
Methods: To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11.
Results: In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone.
Conclusions: The present work provides a promising therapeutic strategy for the targeted treatment of HCC.
{"title":"Fe<sup>3+</sup>-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma.","authors":"Youmei Xiao, Zhanxue Xu, Yuan Cheng, Rufan Huang, Yuan Xie, Hsiang-I Tsai, Hualian Zha, Lifang Xi, Kai Wang, Xiaoli Cheng, Yanfeng Gao, Changhua Zhang, Fang Cheng, Hongbo Chen","doi":"10.1186/s40824-023-00401-x","DOIUrl":"https://doi.org/10.1186/s40824-023-00401-x","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells.</p><p><strong>Methods: </strong>To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe<sup>3+</sup> and encapsulated SOR (SOR@TF-Fe<sup>3+</sup> NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe<sup>3+</sup> and enhanced SOR efficacy by inhibiting the SLC7A11.</p><p><strong>Results: </strong>In vivo and in vitro experiments revealed that SOR@TF-Fe<sup>3+</sup> NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe<sup>3+</sup> NVs accelerated Fe<sup>3+</sup> absorption and transformation in HCC cells. Importantly, SOR@TF-Fe<sup>3+</sup> NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe<sup>3+</sup> NVs alone.</p><p><strong>Conclusions: </strong>The present work provides a promising therapeutic strategy for the targeted treatment of HCC.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"63"},"PeriodicalIF":11.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10120727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-27DOI: 10.1186/s40824-023-00396-5
Yoon-Young Go, Chan-Mi Lee, Sung-Won Chae, Jae-Jun Song
Background: Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs.
Methods: We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs.
Results: TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway.
Conclusion: The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.
{"title":"Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells.","authors":"Yoon-Young Go, Chan-Mi Lee, Sung-Won Chae, Jae-Jun Song","doi":"10.1186/s40824-023-00396-5","DOIUrl":"https://doi.org/10.1186/s40824-023-00396-5","url":null,"abstract":"<p><strong>Background: </strong>Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs.</p><p><strong>Methods: </strong>We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs.</p><p><strong>Results: </strong>TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway.</p><p><strong>Conclusion: </strong>The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"62"},"PeriodicalIF":11.3,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9720461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-27DOI: 10.1186/s40824-023-00407-5
Zhiyong Chen, Yu Chen, Yang Wang, JiaJia Deng, Xin Wang, Qingqing Wang, Yuehua Liu, Jiandong Ding, Lin Yu
Background: Good osseointegration is the key to the long-term stability of bone implants. Thermoplastic polyetheretherketone (PEEK) has been widely used in orthopedics; however, its inherent biological inertia causes fibrous tissue to wrap its surface, which leads to poor osseointegration and thus greatly limits its clinical applications.
Methods: Herein, we developed a facile yet effective surface modification strategy. A commonly used sulfonation coupled with "cold pressing" treatment in the presence of porogenic agent formed a three-dimensional hierarchical porous structure on PEEK surface. Subsequently, the effects of porous surface on the in vitro adhesion, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) were evaluated. Finally, the osteoinduction and osseointegration of surface-porous PEEK implant were examined in the rat distal femoral defect model.
Results: In vitro results showed that the surface modification did not significantly affect the mechanical performance and cytocompatibility of PEEK substance, and the porous structure on the modified PEEK substrate provided space for cellular ingrowth and enhanced osteogenic differentiation and mineralization of BMSCs. In vivo tests demonstrated that the surface-porous PEEK implant could effectively promote new bone formation and had higher bone-implant contact rate, thereby achieving good bone integration with the surrounding host bone. In addition, this modification technique was also successfully demonstrated on a medical PEEK interbody fusion cage.
Conclusion: The present study indicates that topological morphology plays a pivotal role in determining implant osseointegration and this facile and effective modification strategy developed by us is expected to achieve practical applications quickly.
{"title":"Polyetheretherketone implants with hierarchical porous structure for boosted osseointegration.","authors":"Zhiyong Chen, Yu Chen, Yang Wang, JiaJia Deng, Xin Wang, Qingqing Wang, Yuehua Liu, Jiandong Ding, Lin Yu","doi":"10.1186/s40824-023-00407-5","DOIUrl":"https://doi.org/10.1186/s40824-023-00407-5","url":null,"abstract":"<p><strong>Background: </strong>Good osseointegration is the key to the long-term stability of bone implants. Thermoplastic polyetheretherketone (PEEK) has been widely used in orthopedics; however, its inherent biological inertia causes fibrous tissue to wrap its surface, which leads to poor osseointegration and thus greatly limits its clinical applications.</p><p><strong>Methods: </strong>Herein, we developed a facile yet effective surface modification strategy. A commonly used sulfonation coupled with \"cold pressing\" treatment in the presence of porogenic agent formed a three-dimensional hierarchical porous structure on PEEK surface. Subsequently, the effects of porous surface on the in vitro adhesion, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) were evaluated. Finally, the osteoinduction and osseointegration of surface-porous PEEK implant were examined in the rat distal femoral defect model.</p><p><strong>Results: </strong>In vitro results showed that the surface modification did not significantly affect the mechanical performance and cytocompatibility of PEEK substance, and the porous structure on the modified PEEK substrate provided space for cellular ingrowth and enhanced osteogenic differentiation and mineralization of BMSCs. In vivo tests demonstrated that the surface-porous PEEK implant could effectively promote new bone formation and had higher bone-implant contact rate, thereby achieving good bone integration with the surrounding host bone. In addition, this modification technique was also successfully demonstrated on a medical PEEK interbody fusion cage.</p><p><strong>Conclusion: </strong>The present study indicates that topological morphology plays a pivotal role in determining implant osseointegration and this facile and effective modification strategy developed by us is expected to achieve practical applications quickly.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"61"},"PeriodicalIF":11.3,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-22DOI: 10.1186/s40824-023-00403-9
Dahong Kim, Seona Jo, Dongjin Lee, Seok-Min Kim, Ji Min Seok, Seon Ju Yeo, Jun Hee Lee, Jae Jong Lee, Kangwon Lee, Tae-Don Kim, Su A Park
Background: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results.
Method: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels.
Results: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model.
Conclusion: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.
{"title":"NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy.","authors":"Dahong Kim, Seona Jo, Dongjin Lee, Seok-Min Kim, Ji Min Seok, Seon Ju Yeo, Jun Hee Lee, Jae Jong Lee, Kangwon Lee, Tae-Don Kim, Su A Park","doi":"10.1186/s40824-023-00403-9","DOIUrl":"https://doi.org/10.1186/s40824-023-00403-9","url":null,"abstract":"<p><strong>Background: </strong>Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results.</p><p><strong>Method: </strong>To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels.</p><p><strong>Results: </strong>It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model.</p><p><strong>Conclusion: </strong>We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"60"},"PeriodicalIF":11.3,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10089089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-21DOI: 10.1186/s40824-023-00404-8
Ashok Kumar Jangid, Sungjun Kim, Kyobum Kim
Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell-cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell-surface modulation, a few cell recognition moieties, and how their interplay in cell-cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications.
{"title":"Polymeric biomaterial-inspired cell surface modulation for the development of novel anticancer therapeutics.","authors":"Ashok Kumar Jangid, Sungjun Kim, Kyobum Kim","doi":"10.1186/s40824-023-00404-8","DOIUrl":"https://doi.org/10.1186/s40824-023-00404-8","url":null,"abstract":"<p><p>Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell-cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell-surface modulation, a few cell recognition moieties, and how their interplay in cell-cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"59"},"PeriodicalIF":11.3,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10068403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}