Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis
Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/453 |
| _version_ | 1797539822261239808 |
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| author | Camilla Kofoed Andersen Sangita Khatri Jonas Hansen Sofie Slott Rohith Pavan Parvathaneni Ana C. Mendes Ioannis S. Chronakis Shu-Chen Hung Narendiran Rajasekaran Zhuoran Ma Shoujun Zhu Hongjie Dai Elizabeth D. Mellins Kira Astakhova |
| author_facet | Camilla Kofoed Andersen Sangita Khatri Jonas Hansen Sofie Slott Rohith Pavan Parvathaneni Ana C. Mendes Ioannis S. Chronakis Shu-Chen Hung Narendiran Rajasekaran Zhuoran Ma Shoujun Zhu Hongjie Dai Elizabeth D. Mellins Kira Astakhova |
| author_sort | Camilla Kofoed Andersen |
| collection | DOAJ |
| description | Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded with MTX. The coupling efficiency (CE%) of MTX is 77–79% for HiPco-SWCNT and 71–83% for carboxyl-SWCNT. siRNA is noncovalently attached to the nanotubes with efficiency of 90–97% for HiPco-SWCNT and 87–98% for carboxyl-SWCNT. Through whole body imaging in the second near-infrared window (NIR-II window, 1000–1700 nm), SWCNTs were found to be selectively accumulated in inflamed joints in a serum transfer mouse model. We further investigated the interactions of the siRNA/MTX loaded nanotubes with human blood and mice bone marrow cells. In human blood, both types of unloaded SWCNTs were associated with B cells, monocytes and neutrophils. Interestingly, loading with MTX suppressed SWCNTs targeting specificity to immune cells, especially B cells; in contrast, loading siRNA alone enhanced the targeting specificity. Loading both MTX and siRNA to carboxyl-SWCNT enhanced targeting specificity to neutrophils and monocytes but not B cells. The targeting specificity of SWCNTs can potentially be adjusted by altering the ratio of MTX and siRNA loaded. The combined results show that carbon nanotubes have the potential for delivery of cargo drugs specifically to immune cells involved in rheumatoid arthritis. |
| first_indexed | 2024-03-10T12:51:19Z |
| format | Article |
| id | doaj.art-745be840b5eb4af9bd57bb5d20ab58de |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:51:19Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-745be840b5eb4af9bd57bb5d20ab58de2023-11-21T13:02:34ZengMDPI AGPharmaceutics1999-49232021-03-0113445310.3390/pharmaceutics13040453Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid ArthritisCamilla Kofoed Andersen0Sangita Khatri1Jonas Hansen2Sofie Slott3Rohith Pavan Parvathaneni4Ana C. Mendes5Ioannis S. Chronakis6Shu-Chen Hung7Narendiran Rajasekaran8Zhuoran Ma9Shoujun Zhu10Hongjie Dai11Elizabeth D. Mellins12Kira Astakhova13Department of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkDepartment of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkDepartment of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkDepartment of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkDepartment of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkDTU-Food, Technical University of Denmark, Kemitorvet 202, 2800 Kongens Lyngby, DenmarkDTU-Food, Technical University of Denmark, Kemitorvet 202, 2800 Kongens Lyngby, DenmarkDepartment of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86004, USADepartment of Chemistry, Stanford University, Stanford, CA 94305, USADepartment of Chemistry, Stanford University, Stanford, CA 94305, USADepartment of Chemistry, Stanford University, Stanford, CA 94305, USADepartment of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, DenmarkTwo types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded with MTX. The coupling efficiency (CE%) of MTX is 77–79% for HiPco-SWCNT and 71–83% for carboxyl-SWCNT. siRNA is noncovalently attached to the nanotubes with efficiency of 90–97% for HiPco-SWCNT and 87–98% for carboxyl-SWCNT. Through whole body imaging in the second near-infrared window (NIR-II window, 1000–1700 nm), SWCNTs were found to be selectively accumulated in inflamed joints in a serum transfer mouse model. We further investigated the interactions of the siRNA/MTX loaded nanotubes with human blood and mice bone marrow cells. In human blood, both types of unloaded SWCNTs were associated with B cells, monocytes and neutrophils. Interestingly, loading with MTX suppressed SWCNTs targeting specificity to immune cells, especially B cells; in contrast, loading siRNA alone enhanced the targeting specificity. Loading both MTX and siRNA to carboxyl-SWCNT enhanced targeting specificity to neutrophils and monocytes but not B cells. The targeting specificity of SWCNTs can potentially be adjusted by altering the ratio of MTX and siRNA loaded. The combined results show that carbon nanotubes have the potential for delivery of cargo drugs specifically to immune cells involved in rheumatoid arthritis.https://www.mdpi.com/1999-4923/13/4/453carbon nanotubesrheumatoid arthritissiRNA |
| spellingShingle | Camilla Kofoed Andersen Sangita Khatri Jonas Hansen Sofie Slott Rohith Pavan Parvathaneni Ana C. Mendes Ioannis S. Chronakis Shu-Chen Hung Narendiran Rajasekaran Zhuoran Ma Shoujun Zhu Hongjie Dai Elizabeth D. Mellins Kira Astakhova Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis Pharmaceutics carbon nanotubes rheumatoid arthritis siRNA |
| title | Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis |
| title_full | Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis |
| title_fullStr | Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis |
| title_full_unstemmed | Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis |
| title_short | Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis |
| title_sort | carbon nanotubes potent carriers for targeted drug delivery in rheumatoid arthritis |
| topic | carbon nanotubes rheumatoid arthritis siRNA |
| url | https://www.mdpi.com/1999-4923/13/4/453 |
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