Pub Date : 2024-11-16DOI: 10.1016/j.nano.2024.102795
Minzhi Yu, Saatvik Vaishnav, Kristen Hong Dorsey, May Thazin Phoo, Antonela Rodriguez, Anna Schwendeman
Apolipoprotein-based, synthetic high-density lipoprotein (sHDL) nanodiscs have been extensively studied as a potential therapeutic agent for cardiovascular disease due to their ability to promote reverse cholesterol transport. Recently, polymer-based nanodiscs have been made possible with the development of novel polymeric materials such as styrene-maleic anhydride copolymer (SMA). While the polymer-based nanodiscs resemble the discoidal structure of sHDLs, their functional similarity with sHDL has not been investigated. In the present study, we compared the SMA-based and peptide-based sHDL nanodiscs focusing on their cholesterol mobilization effects. Results showed that SMA-based nanoparticles presented similar particle size and in vitro cholesterol efflux effect to those of sHDL nanodiscs. However, SMA nanodiscs induced less cholesterol mobilization in vivo, possibly due to insufficient cholesterol esterification by lecithin:cholesterol acyltransferase.
以载脂蛋白为基础的合成高密度脂蛋白（sHDL）纳米盘因其促进胆固醇逆向运输的能力，已作为心血管疾病的潜在治疗药物被广泛研究。最近，随着苯乙烯-马来酸酐共聚物（SMA）等新型聚合物材料的开发，以聚合物为基础的纳米盘成为可能。虽然聚合物基纳米盘与 sHDL 的盘状结构相似，但它们与 sHDL 的功能相似性尚未得到研究。在本研究中，我们比较了基于 SMA 和基于肽的 sHDL 纳米盘，重点研究了它们的胆固醇动员效应。结果表明，基于 SMA 的纳米颗粒与基于 sHDL 的纳米微粒具有相似的粒径和体外胆固醇外排效果。然而，SMA 纳米微粒在体内诱导的胆固醇迁移率较低，这可能是由于卵磷脂：胆固醇酰基转移酶对胆固醇的酯化作用不足。
{"title":"Comparison of cholesterol transport capacity of peptide- and polymer-based lipid Nanodiscs.","authors":"Minzhi Yu, Saatvik Vaishnav, Kristen Hong Dorsey, May Thazin Phoo, Antonela Rodriguez, Anna Schwendeman","doi":"10.1016/j.nano.2024.102795","DOIUrl":"10.1016/j.nano.2024.102795","url":null,"abstract":"<p><p>Apolipoprotein-based, synthetic high-density lipoprotein (sHDL) nanodiscs have been extensively studied as a potential therapeutic agent for cardiovascular disease due to their ability to promote reverse cholesterol transport. Recently, polymer-based nanodiscs have been made possible with the development of novel polymeric materials such as styrene-maleic anhydride copolymer (SMA). While the polymer-based nanodiscs resemble the discoidal structure of sHDLs, their functional similarity with sHDL has not been investigated. In the present study, we compared the SMA-based and peptide-based sHDL nanodiscs focusing on their cholesterol mobilization effects. Results showed that SMA-based nanoparticles presented similar particle size and in vitro cholesterol efflux effect to those of sHDL nanodiscs. However, SMA nanodiscs induced less cholesterol mobilization in vivo, possibly due to insufficient cholesterol esterification by lecithin:cholesterol acyltransferase.</p>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":" ","pages":"102795"},"PeriodicalIF":4.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Orthopaedic medicine often treats intervertebral disc degeneration (IVDD), which is caused by nucleus pulposus (NP) tissue damage and mechanical stress. Bioactive glasses (BGs), widely used for bone regeneration, can incorporate therapeutic ions into their network. Manganese (Mn) activates human osteoblast integrins, proliferation, and spreading. The CMnBGNPs-NPMSCs are carboxymethyl cellulose hydrogels functionalized with MnBGsNPs and NP-derived mesenchymal stem cells to treat IVDD. To ensure stability and biocompatibility of CMnBGNPs-NPMSCs were characterized for rheological properties like gelation time and swelling ratio. Gene expression analysis of PAX1, FOXF1, CA12, HBB, and OVOS2 via qRT-PCR further assessed the hydrogel's characteristics. Rat models with induced IVDD had hydrogel-MSC composite injected into their intervertebral discs for in vivo studies. Histological examination, immunohistochemical staining for inflammation and disc regeneration markers, and disc height assessments assessed therapeutic efficacy. CMnBGNPs-NPMSCs show promising results for IVDD treatment, offering a novel therapeutic strategy with clinical implications for degenerative disc diseases.
{"title":"Facile fabrication of nano-bioactive glass functionalized blended hydrogel with nucleus pulposus-derived MSCs to improve regeneration potential in treatment of disc degeneration by in vivo rat model.","authors":"Chong Bian, Guangnan Chen, Xiangyang Cheng, Huijie Gu, Zhongyue Huang, Kaifeng Zhou","doi":"10.1016/j.nano.2024.102790","DOIUrl":"10.1016/j.nano.2024.102790","url":null,"abstract":"<p><p>Orthopaedic medicine often treats intervertebral disc degeneration (IVDD), which is caused by nucleus pulposus (NP) tissue damage and mechanical stress. Bioactive glasses (BGs), widely used for bone regeneration, can incorporate therapeutic ions into their network. Manganese (Mn) activates human osteoblast integrins, proliferation, and spreading. The CMnBGNPs-NPMSCs are carboxymethyl cellulose hydrogels functionalized with MnBGsNPs and NP-derived mesenchymal stem cells to treat IVDD. To ensure stability and biocompatibility of CMnBGNPs-NPMSCs were characterized for rheological properties like gelation time and swelling ratio. Gene expression analysis of PAX1, FOXF1, CA12, HBB, and OVOS2 via qRT-PCR further assessed the hydrogel's characteristics. Rat models with induced IVDD had hydrogel-MSC composite injected into their intervertebral discs for in vivo studies. Histological examination, immunohistochemical staining for inflammation and disc regeneration markers, and disc height assessments assessed therapeutic efficacy. CMnBGNPs-NPMSCs show promising results for IVDD treatment, offering a novel therapeutic strategy with clinical implications for degenerative disc diseases.</p>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":" ","pages":"102790"},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.nano.2024.102789
Jing Wang PhD, MD , Bing Chen MSc , Jiezhen Yang MSc , Qin Tang MSc , Yan Zhong MSc , Jiyu Du MSc , Sheng Wang MSc , Qiang Wu PhD, MD , Yang Lu PhD , Yonghong Song PhD
Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.
{"title":"Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a","authors":"Jing Wang PhD, MD , Bing Chen MSc , Jiezhen Yang MSc , Qin Tang MSc , Yan Zhong MSc , Jiyu Du MSc , Sheng Wang MSc , Qiang Wu PhD, MD , Yang Lu PhD , Yonghong Song PhD","doi":"10.1016/j.nano.2024.102789","DOIUrl":"10.1016/j.nano.2024.102789","url":null,"abstract":"<div><div>Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC<sub>50</sub> values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKT<sup>Thr308</sup> site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102789"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.nano.2024.102787
Shamil Akhmedov PhD, MD , Ivan Stepanov MD , Sergey Afanasyev PhD, MD , Sergei Tverdokhlebov PhD , Victor Filimonov PhD , Nikolay Kamenshchikov MD , Anatoly Yermakov PhD , Suowen Xu PhD , Natalia Afanasyeva MD , Boris Kozlov PhD, MD
The use of chemically modified nanocomposites for atherosclerotic plaques can open up new opportunities for studying their effect on changing the structure of the plaque itself. It was shown on the model of the greater omentum of two groups of experimental animals (rats n = 30), which were implanted with Fe@C NPs nanocomposites of 10–30 Nm size into the omentum area. Group 1 (n = 15) consisted of animals that were implanted with chemically modified Fe@C NPs nanocomposites and control group 2 (n = 15) was with non-modified Fe@C NPs nanocomposites. After 1, 2 and 3 weeks we conducted the morphological study of changes in the structure of the omentum using two dyes (Nile Blue and Sudan III), which are specific for adipose tissue. Chemically modified nanocomposites have demonstrated, in contrast to non-modified nanoparticles, to cause morphological changes in the structure of the greater omentum accompanied by the probable release of a similar antiatherogenic factor.
{"title":"Conceptual rationale for the use of chemically modified nanocomposites for active influence on atherosclerosis using the greater omentum model of experimental animals","authors":"Shamil Akhmedov PhD, MD , Ivan Stepanov MD , Sergey Afanasyev PhD, MD , Sergei Tverdokhlebov PhD , Victor Filimonov PhD , Nikolay Kamenshchikov MD , Anatoly Yermakov PhD , Suowen Xu PhD , Natalia Afanasyeva MD , Boris Kozlov PhD, MD","doi":"10.1016/j.nano.2024.102787","DOIUrl":"10.1016/j.nano.2024.102787","url":null,"abstract":"<div><div>The use of chemically modified nanocomposites for atherosclerotic plaques can open up new opportunities for studying their effect on changing the structure of the plaque itself. It was shown on the model of the greater omentum of two groups of experimental animals (rats n = 30), which were implanted with Fe@C NPs nanocomposites of 10–30 Nm size into the omentum area. Group 1 (n = 15) consisted of animals that were implanted with chemically modified Fe@C NPs nanocomposites and control group 2 (n = 15) was with non-modified Fe@C NPs nanocomposites. After 1, 2 and 3 weeks we conducted the morphological study of changes in the structure of the omentum using two dyes (Nile Blue and Sudan III), which are specific for adipose tissue. Chemically modified nanocomposites have demonstrated, in contrast to non-modified nanoparticles, to cause morphological changes in the structure of the greater omentum accompanied by the probable release of a similar antiatherogenic factor.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102787"},"PeriodicalIF":4.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).
{"title":"Preparation of cubic liquid crystal nanoparticles of puerarin and its protective effect on ischemic stroke","authors":"Jingbao Chen MD , Yuhang Xu MD , Yue Liu MD , Yun Meng MD , Long Wu MD , Wenxuan Cao MD , Dayuan Jiang MD , Xiaoqin Chu PhD","doi":"10.1016/j.nano.2024.102786","DOIUrl":"10.1016/j.nano.2024.102786","url":null,"abstract":"<div><div>The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102786"},"PeriodicalIF":4.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.nano.2024.102788
Jan Jakub Kęsik PhD , Wiesław Paja PhD , Pawel Jakubczyk Prof. , Maryna Khalavka PhD , Piotr Terlecki Prof. , Marek Iłżecki PhD. , Wioletta Rzad MSc , Joanna Depciuch PhD
Atherosclerotic carotid stenosis (ACS) is a recognized risk factor for ischemic stroke. Currently, the gold diagnostic standard is Doppler ultrasound, the results of which do not provide certainty whether a given person should be qualified for surgery or not, because in some patients, carotid artery stenosis, for example at the level of 70 %, does not cause ischemic stroke in others yes. Therefore, there is a need for new methods that will clearly indicate the marker qualifying the patient for surgery. In this article we used Fourier Transform InfraRed Attenuated Total Reflectance (FTIR-ATR) spectra of serum collected from healthy and patients suffering from ACS, which had surgery were analyzed by machine learning and Principal Component Analysis (PCA) to determine chemical differences and spectroscopy marker of ACS. PCA demonstrated clearly differentiation between serum collected from healthy and non-healthy patients. Obtained results showed that in serum collected from ACS patients, higher absorbances of PO2− stretching symmetric, CH2 and CH3 symmetric and asymmetric and amide I vibrations were noticed than in control group. Moreover, lack of peak at 1106 cm−1 was observed in spectrum of serum from non-control group. As a result of spectral shifts analysis was found that the most important role in distinguishing between healthy and unhealthy patients is played by FTIR ranges caused by vibrations of PO2− phospholipids, amides III, II and CO lipid vibrations. Continuing, peaks at 1636 cm−1 and 2963 cm−1 were proposed as a potential spectroscopy markers of ACS. Finally, accuracy of obtained results higher than 90 % suggested, that FTIR-ATR can be used as an additional diagnostic tool in ACS qualifying for surgery.
{"title":"Determination of spectroscopy marker of atherosclerotic carotid stenosis using FTIR-ATR combined with machine learning and chemometrics analyses","authors":"Jan Jakub Kęsik PhD , Wiesław Paja PhD , Pawel Jakubczyk Prof. , Maryna Khalavka PhD , Piotr Terlecki Prof. , Marek Iłżecki PhD. , Wioletta Rzad MSc , Joanna Depciuch PhD","doi":"10.1016/j.nano.2024.102788","DOIUrl":"10.1016/j.nano.2024.102788","url":null,"abstract":"<div><div>Atherosclerotic carotid stenosis (ACS) is a recognized risk factor for ischemic stroke. Currently, the gold diagnostic standard is Doppler ultrasound, the results of which do not provide certainty whether a given person should be qualified for surgery or not, because in some patients, carotid artery stenosis, for example at the level of 70 %, does not cause ischemic stroke in others yes. Therefore, there is a need for new methods that will clearly indicate the marker qualifying the patient for surgery. In this article we used Fourier Transform InfraRed Attenuated Total Reflectance (FTIR-ATR) spectra of serum collected from healthy and patients suffering from ACS, which had surgery were analyzed by machine learning and Principal Component Analysis (PCA) to determine chemical differences and spectroscopy marker of ACS. PCA demonstrated clearly differentiation between serum collected from healthy and non-healthy patients. Obtained results showed that in serum collected from ACS patients, higher absorbances of PO<sup>2−</sup> stretching symmetric, CH<sub>2</sub> and CH<sub>3</sub> symmetric and asymmetric and amide I vibrations were noticed than in control group. Moreover, lack of peak at 1106 cm<sup>−1</sup> was observed in spectrum of serum from non-control group. As a result of spectral shifts analysis was found that the most important role in distinguishing between healthy and unhealthy patients is played by FTIR ranges caused by vibrations of PO<sup>2−</sup> phospholipids, amides III, II and C<img>O lipid vibrations. Continuing, peaks at 1636 cm<sup>−1</sup> and 2963 cm<sup>−1</sup> were proposed as a potential spectroscopy markers of ACS. Finally, accuracy of obtained results higher than 90 % suggested, that FTIR-ATR can be used as an additional diagnostic tool in ACS qualifying for surgery.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102788"},"PeriodicalIF":4.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20DOI: 10.1016/j.nano.2024.102785
Iaroslav Gnilitskyi PhD , Leonid Dolgov PhD , Aile Tamm PhD , Ana Maria Ferraria PhD , Kateryna Diedkova PhD , Sergei Kopanchuk PhD , Yaroslav Tsekhmister PhD , Santa Veiksina PhD , Vincent Polewczyk PhD , Maksym Pogorielov PhD
Dental and orthopedic implants have become routine medical technologies for tooth replacement and bone fixation. Despite significant progress in implantology, achieving sufficient osseointegration remains a challenge, often leading to implant failure over the long term. Nanotechnology offers the potential to mimic the natural patterns of living tissues, providing a promising platform for tissue engineering and implant surface design. Among the various methods for developing nanostructures, High-Regular Laser-Induced Periodic Surface Structures (HR-LIPSS) techniques stand out for their ability to fabricate highly ordered nanostructures with excellent long-range repeatability and production efficiency. In this study, we utilized an innovative technical approach to generate traditional laser-induced superficial LIPSS nanostructures, followed by detailed surface analysis using classical microscopy and physicochemical methods. Our findings demonstrate for the first time that nanostructured LIPSS surfaces can significantly enhance cell adhesion and proliferation while providing an optimal environment for cell metabolism. Given the high reproducibility, low cost, and potential of HR-LIPSS techniques to support cell growth and differentiation, this novel technology has the potential to impact both the industrial development of new implants and clinical outcomes after implantation.
{"title":"Enhanced osteointegration and osteogenesis of osteoblast cells by laser-induced surface modification of Ti implants","authors":"Iaroslav Gnilitskyi PhD , Leonid Dolgov PhD , Aile Tamm PhD , Ana Maria Ferraria PhD , Kateryna Diedkova PhD , Sergei Kopanchuk PhD , Yaroslav Tsekhmister PhD , Santa Veiksina PhD , Vincent Polewczyk PhD , Maksym Pogorielov PhD","doi":"10.1016/j.nano.2024.102785","DOIUrl":"10.1016/j.nano.2024.102785","url":null,"abstract":"<div><div>Dental and orthopedic implants have become routine medical technologies for tooth replacement and bone fixation. Despite significant progress in implantology, achieving sufficient osseointegration remains a challenge, often leading to implant failure over the long term. Nanotechnology offers the potential to mimic the natural patterns of living tissues, providing a promising platform for tissue engineering and implant surface design. Among the various methods for developing nanostructures, High-Regular Laser-Induced Periodic Surface Structures (HR-LIPSS) techniques stand out for their ability to fabricate highly ordered nanostructures with excellent long-range repeatability and production efficiency. In this study, we utilized an innovative technical approach to generate traditional laser-induced superficial LIPSS nanostructures, followed by detailed surface analysis using classical microscopy and physicochemical methods. Our findings demonstrate for the first time that nanostructured LIPSS surfaces can significantly enhance cell adhesion and proliferation while providing an optimal environment for cell metabolism. Given the high reproducibility, low cost, and potential of HR-LIPSS techniques to support cell growth and differentiation, this novel technology has the potential to impact both the industrial development of new implants and clinical outcomes after implantation.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102785"},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1016/j.nano.2024.102784
Elisa Schiavon MSc , Sara Rezzola PhD , Erica Filippi MSc , Marta Turati PhD , Sofia Parrasia PhD , Simone Bernardotto MSc , Martina Stocco MSc , Ildikò Szabò PhD , Andrea Mattarei PhD , Roberto Ronca PhD , Margherita Morpurgo PhD
In targeted cancer therapy, antibody-drug-conjugates using mertansine (DM1)-based cytotoxic compounds rely on covalent bonds for drug conjugation. Consequently, the cytotoxic DM1 derivative released upon their proteolytic digestion is up to 1000-fold less potent than DM1 and lacks a bystander effect. To overcome these limitations, we developed a DM1 derivative (keto-DM1) suitable for bioconjugation through an acid-reversible hydrazone bond. Its acid-reversible hydrazone conjugate with biotin (B-Hz-DM1) was generated and tested for efficacy using the cetuximab-targeted Avidin-Nucleic-Acid-NanoASsembly (ANANAS) nanoparticle (NP) platform.
NP-tethered B-Hz-DM1 is stable at neutral pH and releases its active moiety only in endosome/lysosome mimicking acidic pH. In vitro, the NP/Cetux/B-Hz-DM1 assembly showed high potency on MDA-MB231 breast cancer cells. In vivo both B-Hz-DM1 and NP/Cetux/B-Hz-DM1 reduced tumor growth. A significantly major effect was exerted by the nanoformulation, associated with an increased in situ tumor cell death. Keto-DM1 is a promising acid-reversible mertansine derivative for targeted delivery in cancer therapy.
{"title":"A novel mertansine conjugate for acid-reversible targeted drug delivery validated through the Avidin-Nucleic-Acid-NanoASsembly platform","authors":"Elisa Schiavon MSc , Sara Rezzola PhD , Erica Filippi MSc , Marta Turati PhD , Sofia Parrasia PhD , Simone Bernardotto MSc , Martina Stocco MSc , Ildikò Szabò PhD , Andrea Mattarei PhD , Roberto Ronca PhD , Margherita Morpurgo PhD","doi":"10.1016/j.nano.2024.102784","DOIUrl":"10.1016/j.nano.2024.102784","url":null,"abstract":"<div><p>In targeted cancer therapy, antibody-drug-conjugates using mertansine (DM1)-based cytotoxic compounds rely on covalent bonds for drug conjugation. Consequently, the cytotoxic DM1 derivative released upon their proteolytic digestion is up to 1000-fold less potent than DM1 and lacks a bystander effect. To overcome these limitations, we developed a DM1 derivative (keto-DM1) suitable for bioconjugation through an acid-reversible hydrazone bond. Its acid-reversible hydrazone conjugate with biotin (B-Hz-DM1) was generated and tested for efficacy using the cetuximab-targeted Avidin-Nucleic-Acid-NanoASsembly (ANANAS) nanoparticle (NP) platform.</p><p>NP-tethered B-Hz-DM1 is stable at neutral pH and releases its active moiety only in endosome/lysosome mimicking acidic pH. <em>In vitro</em>, the NP/Cetux/B-Hz-DM1 assembly showed high potency on MDA-MB231 breast cancer cells. <em>In vivo</em> both B-Hz-DM1 and NP/Cetux/B-Hz-DM1 reduced tumor growth. A significantly major effect was exerted by the nanoformulation, associated with an increased <em>in situ</em> tumor cell death. Keto-DM1 is a promising acid-reversible mertansine derivative for targeted delivery in cancer therapy.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102784"},"PeriodicalIF":4.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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