Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis

Camilla Kofoed Andersen,Shoujun Zhu,Jonas Hansen,Sofie Slott,Narendiran Rajasekaran,Ioannis S Chronakis,Elizabeth D Mellins,Hongjie Dai,Rohith Pavan Parvathaneni,Kira Astakhova,Zhuoran Ma,Ana C Mendes,Shu-Chen Hung,Sangita Khatri

doi:10.3390/pharmaceutics13040453

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.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects 0.5–1% of the adult population worldwide, predominantly affecting women and the elderly [1]
We studied solubilized HiPco-single wall carbon nanotubes (SWCNTs) and HiPco-SWCNTs by scanning electron microscopy (SEM; Figure 6)
12 different nanotube products were synthesized composed of HiPcoSWCNTs or carboxyl-SWCNTs in combination with a NOTCH1 small interfering RNA (siRNA) and/or MTX

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects 0.5–1% of the adult population worldwide, predominantly affecting women and the elderly [1]. RA is primarily characterized by joint swelling that reflects inflammation of synovial membrane, where leukocytes, such as neutrophils, monocytes, T cells, and B cells, are recruited to trigger onset of RA and lead to destruction of cartilage and bone [1,3]. The most commonly used therapies for managing RA are disease-modifying antirheumatic drugs (DMARDs) [4]. These drugs slow disease progression and can potentially save joints and tissues from permanent damage.

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