Carbon Nanotubes-Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis.
Camilla Kofoed AndersenSangita KhatriJonas HansenSofie SlottRohith Pavan ParvathaneniAna C MendesIoannis S ChronakisShu-Chen HungNarendiran RajasekaranZhuoran MaShoujun ZhuHongjie DaiElizabeth D MellinsKira AstakhovaPublished in: Pharmaceutics (2021)
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.
Keyphrases
- cancer therapy
- drug delivery
- carbon nanotubes
- rheumatoid arthritis
- bone marrow
- endothelial cells
- drug release
- mouse model
- anti inflammatory
- dendritic cells
- magnetic resonance
- type diabetes
- computed tomography
- induced apoptosis
- emergency department
- mass spectrometry
- high dose
- disease activity
- cell proliferation
- genome wide
- ankylosing spondylitis
- low dose
- walled carbon nanotubes
- systemic sclerosis
- interstitial lung disease
- structural basis
- adipose tissue
- immune response
- induced pluripotent stem cells
- signaling pathway
- atomic force microscopy
- mesenchymal stem cells
- high fat diet induced
- systemic lupus erythematosus
- pi k akt