Ciarán M. Maguire, Michelle Lavin, Mairead Doyle, Mary Byrne, Adriele Prina-Mello, James S. O'Donnell, Yuri Volkov
The size-dependent optical properties of quantum dots (QDs) are frequently exploited for use in medical imaging and labelling applications. Similarly, presented here, they also elicit profound size-dependent anticoagulant properties. Cadmium telluride quantum dot (QDs) (3.2 nm) were shown to have a dramatic anticoagulant effect centred on around the intrinsic coagulation pathway, compared to their 3.6 nm counterparts. Several clinically relevant diagnostic tests were carried out over a concentration range of the QDs and demonstrated that the 3.2 nm QDs elicited their response on the intrinsic pathway as a whole, yet the activity of the individual intrinsic coagulation factors was not affected. The mechanism appears also to be strongly influenced by the concentration of calcium ions and not cadmium ions leached from the QDs. Static and shear-based primary haemostasis assays were also carried out, demonstrating a profound anticoagulant effect which was independent of platelets and phospholipids. The data presented here suggest that the physical–chemical properties of the QDs may have a role in the modulation of haemostasis and the coagulation cascade, in a yet not fully understood mechanism. This study has implications for the use of similar QDs as diagnostic or therapeutic tools in vivo, and for the occupational health and safety of those working with such materials.
{"title":"The anticoagulant properties of cadmium telluride quantum dots","authors":"Ciarán M. Maguire, Michelle Lavin, Mairead Doyle, Mary Byrne, Adriele Prina-Mello, James S. O'Donnell, Yuri Volkov","doi":"10.1002/jin2.35","DOIUrl":"10.1002/jin2.35","url":null,"abstract":"<p>The size-dependent optical properties of quantum dots (QDs) are frequently exploited for use in medical imaging and labelling applications. Similarly, presented here, they also elicit profound size-dependent anticoagulant properties. Cadmium telluride quantum dot (QDs) (3.2 nm) were shown to have a dramatic anticoagulant effect centred on around the intrinsic coagulation pathway, compared to their 3.6 nm counterparts. Several clinically relevant diagnostic tests were carried out over a concentration range of the QDs and demonstrated that the 3.2 nm QDs elicited their response on the intrinsic pathway as a whole, yet the activity of the individual intrinsic coagulation factors was not affected. The mechanism appears also to be strongly influenced by the concentration of calcium ions and not cadmium ions leached from the QDs. Static and shear-based primary haemostasis assays were also carried out, demonstrating a profound anticoagulant effect which was independent of platelets and phospholipids. The data presented here suggest that the physical–chemical properties of the QDs may have a role in the modulation of haemostasis and the coagulation cascade, in a yet not fully understood mechanism. This study has implications for the use of similar QDs as diagnostic or therapeutic tools in vivo<i>,</i> and for the occupational health and safety of those working with such materials.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 1","pages":"16-28"},"PeriodicalIF":0.0,"publicationDate":"2018-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.35","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36253677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susanne Bremer-Hoffmann, Blanka Halamoda-Kenzaoui, Sven Even Borgos
The application of nanotechnology in health care is widely accepted as a potential driver of biomedical innovation. By exploiting their unique physicochemical properties, nanomedicines can monitor, repair, and control biological systems in order to address diseases for which currently no or only insufficient diagnostic and therapeutic tools are available. Nevertheless, the opportunities of nanotechnologies in the health sector are accompanied by challenges in the regulation of these products. Sufficient knowledge on their quality, safety, and efficacy must be gained and standardised methods must be made available to support the regulatory decision making and allow a smooth translation towards clinical applications. We have conducted a survey among regulatory authorities with the aim to obtain a general overview on the status and regulatory needs of nanomedicines and to indicate some trends on future requirements. The outcome has demonstrated strong regional differences in the regulation of nanomedicines and confirmed the need for the harmonisation of information requirements on nano-specific properties. In addition, a number of critical physicochemical properties that have already been proposed in the scientific literature were verified in the survey as relevant for regulatory decision making. Finally, the survey has demonstrated an interest of regulatory agencies in an independent nanomedicine characterisation facility that can support regulators in the evaluation of these systems and at the same time assess the performance of existing and new test methods for their application to the field of nanomedicine.
{"title":"Identification of regulatory needs for nanomedicines","authors":"Susanne Bremer-Hoffmann, Blanka Halamoda-Kenzaoui, Sven Even Borgos","doi":"10.1002/jin2.34","DOIUrl":"10.1002/jin2.34","url":null,"abstract":"<p>The application of nanotechnology in health care is widely accepted as a potential driver of biomedical innovation. By exploiting their unique physicochemical properties, nanomedicines can monitor, repair, and control biological systems in order to address diseases for which currently no or only insufficient diagnostic and therapeutic tools are available. Nevertheless, the opportunities of nanotechnologies in the health sector are accompanied by challenges in the regulation of these products. Sufficient knowledge on their quality, safety, and efficacy must be gained and standardised methods must be made available to support the regulatory decision making and allow a smooth translation towards clinical applications. We have conducted a survey among regulatory authorities with the aim to obtain a general overview on the status and regulatory needs of nanomedicines and to indicate some trends on future requirements. The outcome has demonstrated strong regional differences in the regulation of nanomedicines and confirmed the need for the harmonisation of information requirements on nano-specific properties. In addition, a number of critical physicochemical properties that have already been proposed in the scientific literature were verified in the survey as relevant for regulatory decision making. Finally, the survey has demonstrated an interest of regulatory agencies in an independent nanomedicine characterisation facility that can support regulators in the evaluation of these systems and at the same time assess the performance of existing and new test methods for their application to the field of nanomedicine.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 1","pages":"4-15"},"PeriodicalIF":0.0,"publicationDate":"2018-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42656709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily J. Simpson, Pierangelo Gobbo, Fernanda C. Bononi, Emily Murrell, Mark S. Workentin, Leonard G. Luyt
Cancer targeting can be used for both tumor diagnosis and therapy. Recently, gold nanoparticles (AuNPs) have found utility in this field as they are very small in size, and thus display an enhanced permeability and retention effect, allowing them to be taken up by tumor cells through “passive targeting.” However, this accumulation is non-specific. Conversely, AuNPs functionalized with targeting entities such as peptides, antibodies, or small molecules can specifically target tumors through interaction with cancer-specific protein receptors. In this study, targeted AuNPs were developed using an azide-modified peptide that was able to react with alkyne-functionalized AuNPs through an interfacial strain-promoted azide-alkyne cycloaddition. Small (3 nm) AuNPs were made water-soluble through PEGylation and functionalized with dibenzocyclooctyne to add the alkyne functionality. For the targeting entity, a pan-bombesin peptide ([D-Phe6,β-Ala11,Phe13,Nle14]bombesin(6–14)) was chosen as it binds to all four receptor subtypes of the gastrin releasing peptide receptor, which is highly expressed in prostate cancer. Prostate cancer (PC-3) cells were incubated with the targeted AuNPs and studied via transmission electron microscopy. AuNPs conjugated with bombesin showed higher accumulation in PC-3 cells than either the blocking or control studies. These results suggest that these small, water-soluble, bombesin-functionalized AuNPs have potential applications in targeting prostate cancer as diagnostic or therapeutic entities.
{"title":"Bombesin-functionalized water-soluble gold nanoparticles for targeting prostate cancer","authors":"Emily J. Simpson, Pierangelo Gobbo, Fernanda C. Bononi, Emily Murrell, Mark S. Workentin, Leonard G. Luyt","doi":"10.1002/jin2.33","DOIUrl":"10.1002/jin2.33","url":null,"abstract":"<p>Cancer targeting can be used for both tumor diagnosis and therapy. Recently, gold nanoparticles (AuNPs) have found utility in this field as they are very small in size, and thus display an enhanced permeability and retention effect, allowing them to be taken up by tumor cells through “passive targeting.” However, this accumulation is non-specific. Conversely, AuNPs functionalized with targeting entities such as peptides, antibodies, or small molecules can specifically target tumors through interaction with cancer-specific protein receptors. In this study, targeted AuNPs were developed using an azide-modified peptide that was able to react with alkyne-functionalized AuNPs through an interfacial strain-promoted azide-alkyne cycloaddition. Small (3 nm) AuNPs were made water-soluble through PEGylation and functionalized with dibenzocyclooctyne to add the alkyne functionality. For the targeting entity, a pan-bombesin peptide ([D-Phe<sup>6</sup>,β-Ala<sup>11</sup>,Phe<sup>13</sup>,Nle<sup>14</sup>]bombesin(6–14)) was chosen as it binds to all four receptor subtypes of the gastrin releasing peptide receptor, which is highly expressed in prostate cancer. Prostate cancer (PC-3) cells were incubated with the targeted AuNPs and studied via transmission electron microscopy. AuNPs conjugated with bombesin showed higher accumulation in PC-3 cells than either the blocking or control studies. These results suggest that these small, water-soluble, bombesin-functionalized AuNPs have potential applications in targeting prostate cancer as diagnostic or therapeutic entities.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"2 4","pages":"174-187"},"PeriodicalIF":0.0,"publicationDate":"2017-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43639154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Donnellan, Vicki Stone, Helinor Johnston, Marco Giardiello, Andrew Owen, Steve Rannard, Ghaith Aljayyoussi, Benjamin Swift, Lang Tran, Craig Watkins, Karen Stevenson