Nanofunctionalized Stent-Mediated Local Heat Treatment for the Suppression of Stent-Induced Tissue Hyperplasia

Abstract

Current therapeutic strategies are insufficient for suppressing stent-induced restenosis. Here, branched gold nanoparticles (BGNP)-coated self-expandable metallic stents (SEMSs) were developed for a local heat-induced suppression of stent-related tissue hyperplasia. Our polydopamine (PDA) coating on SEMS allowed BGNP crystal growth on the surface of SEMSs. The prepared BGNP-coated SEMS showed effective local heating under near-infrared laser irradiation. The effectiveness of BGNP-coated SEMSs for suppressing stent-related tissue hyperplasia was demonstrated in a rat esophageal model ( n = 52). BGNP-coated SEMS placement under fluoroscopic guidance was technically successful in all rats. The placed BGNP-coated SEMS in rat esophagus achieved three different local heat dose ranges (50, 65, and 80 °C) under fluoroscopic image-guided local irradiation. Follow-up endoscopic examination readily monitored the local heating and observed significantly decreased tissue hyperplasia at 4 weeks of local heat treatments (50 and 65 °C). Finally, Western blot, histology, immunohistochemistry (HSP70, αSMA, and TUNEL), and immunofluorescence (Ki67 and BrdU) analyses along with the statistical analysis confirmed that optimized BGNP-coated SEMS-mediated local heat treatments inducing the expression of anti-inflammatory HSP70 effectively suppresses tissue hyperplasia after stent placement in the esophagus. Our local heating with nanofunctionalized stents represents a promising new approach for suppressing stent-related tissue hyperplasia.

Metallic Stent Mesh Coated with Silver Nanoparticles Suppresses Stent-Induced Tissue Hyperplasia and Biliary Sludge in the Rabbit Extrahepatic Bile Duct

“…AgNP-coated SEMSs were prepared using a bio-inspired surface modification process ( Scheme 1 ) [ 20 ]. The PDA layer was first coated onto the SEMS surface, and then AgNPs were grown on the PDA surface.…”

“…The stents were 4 mm in diameter and 10 mm in length and had radiopaque markers at both ends. The AgNP coating was added to the surface of nitinol SEMSs using polydopamine (PDA) chemistry ( Table S1, Supplementary Materials ) [ 20 ]. Dopamine hydrochloride (1 mg/mL) was dissolved in 15 mL of 5 mM Tris buffer (pH 8.5).…”

“…The degree of inflammatory cell infiltration was subjectively determined according to the distribution and density of the inflammatory cells (1, mild; 2, mild to moderate; 3, moderate; 4, moderate to severe; and 5, severe). The average values of the thickness of submucosal fibrosis and the degree of inflammatory cell infiltration represented the average value of eight points around the circumference [ 5 , 20 ]. The degree of collagen deposition was determined using MT-stained sections.…”

Photothermal Therapy via a Gold Nanoparticle-Coated Stent for Treating Stent-Induced Granulation Tissue Formation in the Rat Esophagus

“…Histological evaluation using H&E was based on the degree of submucosal in ammatory cell in ltration, the number of epithelial layers, the thickness of the submucosal brosis, and the tissue-hyperplasia-related percentage of the esophageal cross-sectional area of stenosis calculated as 100 × (1 − [stenotic stented area/original stented area]). 6,11 The degree of in ammatory cell in ltration was subjectively determined according to the distribution and density of the in ammatory cells, i.e. graded as 1, mild when there was occasional visible in ltration of single leukocytes; 2, mild-to-moderate when there was patchy in ltration of leukocytes; 3, moderate when coalescing leukocytes made individual loci indistinguishable; 4, moderate-to-severe when there was diffuse in ltration of leukocytes throughout the submucosal layer; and 5, severe when there was diffuse in ltration with multiple necrotic foci.…”

“…[13][14][15][16][17][18] Recently, AuNPbased functionalized stents were introduced to locally treat cancer cells or tissue hyperplasia adjacent to stented non-vascular luminal organs. 11,12,19,20 Park et al have reported in rat models that locally applied temperature increases (50°C to 65°C) successfully suppressed tissue hyperplasia after esophageal and gastroduodenal stent placement. 11,20 We hypothesized that AuNP-coated SEMS could be used for localized PTT under NIR laser irradiation.…”