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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Published inPharmaceutics Vol. 13; no. 4; p. 453
Main Authors Kofoed Andersen, Camilla, Khatri, Sangita, Hansen, Jonas, Slott, Sofie, Pavan Parvathaneni, Rohith, Mendes, Ana C., Chronakis, Ioannis S., Hung, Shu-Chen, Rajasekaran, Narendiran, Ma, Zhuoran, Zhu, Shoujun, Dai, Hongjie, Mellins, Elizabeth D., Astakhova, Kira
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 27.03.2021
MDPI
Subjects
Carbon
carbon nanotubes
Cartilage
Efficiency
Gene therapy
Nanomaterials
Polyethylene glycol
Reagents
Rheumatoid arthritis
siRNA
Tumor necrosis factor-TNF
United States > US
Germany
carbon nanotubes
rheumatoid arthritis
siRNA
Online AccessGet full text
ISSN1999-4923
1999-4923
DOI10.3390/pharmaceutics13040453

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Abstract 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.
AbstractList 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.
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.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.
Author Hansen, Jonas
Hung, Shu-Chen
Chronakis, Ioannis S.
Zhu, Shoujun
Kofoed Andersen, Camilla
Mendes, Ana C.
Pavan Parvathaneni, Rohith
Dai, Hongjie
Slott, Sofie
Rajasekaran, Narendiran
Khatri, Sangita
Ma, Zhuoran
Astakhova, Kira
Mellins, Elizabeth D.
AuthorAffiliation 4 Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86004, USA; Naren.raj@nau.edu
5 Department of Chemistry, Stanford University, Stanford, CA 94305, USA; zma2@stanford.edu (Z.M.); sjzhu@jlu.edu.cn (S.Z.); hdai1@stanford.edu (H.D.)
2 DTU-Food, Technical University of Denmark, Kemitorvet 202, 2800 Kongens Lyngby, Denmark; anac@food.dtu.dk (A.C.M.); ioach@food.dtu.dk (I.S.C.)
1 Department of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, Denmark; millaa@live.dk (C.K.A.); khatrisangita2049@gmail.com (S.K.); jonhan@kemi.dtu.dk (J.H.); sofslo@kemi.dtu.dk (S.S.); s181353@student.dtu.dk (R.P.P.)
3 Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; shung01@amgen.com (S.-C.H.); mellins@stanford.edu (E.D.M.)
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– name: 2 DTU-Food, Technical University of Denmark, Kemitorvet 202, 2800 Kongens Lyngby, Denmark; anac@food.dtu.dk (A.C.M.); ioach@food.dtu.dk (I.S.C.)
– name: 5 Department of Chemistry, Stanford University, Stanford, CA 94305, USA; zma2@stanford.edu (Z.M.); sjzhu@jlu.edu.cn (S.Z.); hdai1@stanford.edu (H.D.)
– name: 1 Department of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, Denmark; millaa@live.dk (C.K.A.); khatrisangita2049@gmail.com (S.K.); jonhan@kemi.dtu.dk (J.H.); sofslo@kemi.dtu.dk (S.S.); s181353@student.dtu.dk (R.P.P.)
– name: 3 Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; shung01@amgen.com (S.-C.H.); mellins@stanford.edu (E.D.M.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33801590$$D View this record in MEDLINE/PubMed
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Snippet Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug...
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StartPage 453
SubjectTerms Carbon
carbon nanotubes
Cartilage
Efficiency
Gene therapy
Nanomaterials
Polyethylene glycol
Reagents
Rheumatoid arthritis
siRNA
Tumor necrosis factor-TNF
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Title Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis
URI https://www.ncbi.nlm.nih.gov/pubmed/33801590
https://www.proquest.com/docview/2530141912
https://www.proquest.com/docview/2508559755
https://pubmed.ncbi.nlm.nih.gov/PMC8066293
https://doaj.org/article/745be840b5eb4af9bd57bb5d20ab58de
Volume 13
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