A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent
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| Title: | A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent |
|---|---|
| Authors: | Ashokan, Anusha1, Menon, Deepthy1, Nair, Shantikumar1, Koyakutty, Manzoor manzoor_nanomed@yahoo.com |
| Source: | Biomaterials. Mar2010, Vol. 31 Issue 9, p2606-2616. 11p. |
| Subjects: | Targeted drug delivery, Hydroxyapatite, Nanocrystals, Molecular biology, Biomarkers, Fluorescence, Magnetic resonance imaging, Cancer treatment |
| Abstract: | Abstract: Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging. Monodispersed nHAp crystals of average size ∼30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth impurities by a surfactant-free, aqueous wet-chemical method at 100 °C. Doping of nHAp with Eu3+ (3 at%) resulted bright near-infrared fluorescence (700 nm) due to efficient 5 D 0–7 F 4 electronic transition and co-doping with Gd3+ resulted enhanced paramagnetic longitudinal relaxivity (r 1 ∼12 mM−1 s−1) suitable for T 1 weighted MR imaging together with ∼80% X-ray attenuation suitable for X-ray contrast imaging. Capability of MF-nHAp to specifically target and enhance the signature of molecular receptors (folate) in cancer cells was realized by carbodiimide grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp conjugates showed specific aggregation on FR+ve cells while leaving the negative control cells untouched. Nanotoxicity evaluation of this multifunctional nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung cancer cell line (A549) revealed no apparent toxicity even upto relatively higher doses of 500 μg/mL and 48 h of incubation. Flow-cytometry based reactive oxygen species (ROS) analysis also showed no significant levels of ROS generation in the nHAp treated cells. The tri-modal contrast imaging functionality together with molecular receptor targeting capability and biocompatibility makes MF-nHAp a promising biomineral contrast agent for combinatorial molecular imaging. [Copyright &y& Elsevier] |
| Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 48024490 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Ashokan%2C+Anusha%22">Ashokan, Anusha</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Menon%2C+Deepthy%22">Menon, Deepthy</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Nair%2C+Shantikumar%22">Nair, Shantikumar</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Koyakutty%2C+Manzoor%22">Koyakutty, Manzoor</searchLink><i> manzoor_nanomed@yahoo.com</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Mar2010, Vol. 31 Issue 9, p2606-2616. 11p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Targeted+drug+delivery%22">Targeted drug delivery</searchLink><br /><searchLink fieldCode="DE" term="%22Hydroxyapatite%22">Hydroxyapatite</searchLink><br /><searchLink fieldCode="DE" term="%22Nanocrystals%22">Nanocrystals</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+biology%22">Molecular biology</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Fluorescence%22">Fluorescence</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+resonance+imaging%22">Magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+treatment%22">Cancer treatment</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract: Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging. Monodispersed nHAp crystals of average size ∼30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth impurities by a surfactant-free, aqueous wet-chemical method at 100 °C. Doping of nHAp with Eu3+ (3 at%) resulted bright near-infrared fluorescence (700 nm) due to efficient 5 D 0–7 F 4 electronic transition and co-doping with Gd3+ resulted enhanced paramagnetic longitudinal relaxivity (r 1 ∼12 mM−1 s−1) suitable for T 1 weighted MR imaging together with ∼80% X-ray attenuation suitable for X-ray contrast imaging. Capability of MF-nHAp to specifically target and enhance the signature of molecular receptors (folate) in cancer cells was realized by carbodiimide grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp conjugates showed specific aggregation on FR+ve cells while leaving the negative control cells untouched. Nanotoxicity evaluation of this multifunctional nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung cancer cell line (A549) revealed no apparent toxicity even upto relatively higher doses of 500 μg/mL and 48 h of incubation. Flow-cytometry based reactive oxygen species (ROS) analysis also showed no significant levels of ROS generation in the nHAp treated cells. The tri-modal contrast imaging functionality together with molecular receptor targeting capability and biocompatibility makes MF-nHAp a promising biomineral contrast agent for combinatorial molecular imaging. [Copyright &y& Elsevier] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.biomaterials.2009.11.113 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 2606 Subjects: – SubjectFull: Targeted drug delivery Type: general – SubjectFull: Hydroxyapatite Type: general – SubjectFull: Nanocrystals Type: general – SubjectFull: Molecular biology Type: general – SubjectFull: Biomarkers Type: general – SubjectFull: Fluorescence Type: general – SubjectFull: Magnetic resonance imaging Type: general – SubjectFull: Cancer treatment Type: general Titles: – TitleFull: A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Ashokan, Anusha – PersonEntity: Name: NameFull: Menon, Deepthy – PersonEntity: Name: NameFull: Nair, Shantikumar – PersonEntity: Name: NameFull: Koyakutty, Manzoor IsPartOfRelationships: – BibEntity: Dates: – D: 20 M: 03 Text: Mar2010 Type: published Y: 2010 Identifiers: – Type: issn-print Value: 01429612 Numbering: – Type: volume Value: 31 – Type: issue Value: 9 Titles: – TitleFull: Biomaterials Type: main |
| ResultId | 1 |
