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

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.

Recent advances in nanoparticle-based drug delivery systems for rheumatoid arthritis treatment

“… 29 Because RGD is an inflammation-targeting moiety, MTX-loaded poly( dl -lactic- co -glycolic acid) (PLGA)-Gold (Au) half-shell nanoparticles (MTX-PLGA-Au) and conjugated arginine-glycine-aspartic acid (RGD) peptides on the surface of the Au half-shell increased the potential of MTX as a RA treatment. 29 Progressively several other nanomedicines were reported as potential candidates for RA therapy like MTX combined with nanoemulsions, 30 siRNA-loaded chitosan nanoparticles, 31 curcumin-loaded carboxy methyl cellulose acetate (CMCAB), 32 exosomes as biomimetic particles, 33 stimuli-responsive liposomes, 34 MTX and siRNA loaded carbon nanotubes, 35 poly(amidoamine) (PAMAM) dendrimers functionalized with chondroitin sulphate and with anti-TNF-α to provide anti-inflammatory properties 36 and mesoporous silica nanoparticles encapsulating dexamethasone 37 to deliver the traditional drugs.…”

Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective

“…Several other studies demonstrated the feasibility of inhibiting Notch signaling by delivering siRNA targeting Notch ligands or receptors in vivo [107][108][109][110]. For example, siNOTCH1loaded nanoparticles significantly inhibit Notch signaling, thereby attenuating rheumatoid arthritis in mouse models [107,110]. Thus, nanoparticle-aided highly effective siRNA showed promising implications in Notch-directed cancer therapy.…”

Design of Double Functionalized Carbon Nanotube for Amphotericin B and Genetic Material Delivery

“…Zhao et al modi ed the surfaces of SWCNT and MWCNT with peptide lipide and sucrose laurate to obtain a siRNA delivery system, which had high temperature-sensitivity and photothermal performance 43 . Kofoed Andersen et al applied two kinds of SWCNT (Hipco-and carboxyl-SWCNT) for methotrexate and a siRNA targeted deliveries 44 . They reported methotrexate e ciencies higher than 70% for both types of SWCNT.…”