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.
Despite the promising
results from the placement of covered or
uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic
option for the malignant gastric outlet obstruction (GOO), the long
patency of the stent is still limited because of stent-induced tissue
hyperplasia. Here, a local heat treatment using a nanofunctionalized
SEMS is proposed for suppressing stent-induced tissue hyperplasia
during GOO treatment. Highly efficient photothermal gold nanoparticle
(GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local
heat treatment in rat gastric outlet. The in vivo heating temperature
in rat gastric outlet model was evaluated and compared with in vitro
heating temperature. Three groups of our developed 45 rat gastric
outlet models were used: group A, noncoated SEMS only; group B, GNP-SEMS
plus local heating; and group C, GNP-SEMS only to investigate in vivo
efficacy of GNP-SEMS mediated local heating. Ten rats per group were
sacrificed for 4 weeks, and five rats per group were sacrificed immediately
after local heat treatment. The in vivo heating temperature was found
to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs
were successfully placed through a percutaneous approach into the
rat gastric outlet (n = 45). The therapeutic effects
of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin,
Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence
(Ki67), and the results showed significant prevention of tissue hyperplasia
following stent placement without adjacent gastrointestinal tissue
damage. GNP-SEMS-mediated local heating could be an alternative therapeutic
option for the suppression of tissue hyperplasia following stent placement
in benign and malignant GOOs.
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