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Nanoparticle-Embedded Electrospun Fiber-Covered Stent to Assist Intraluminal Photodynamic Treatment of Oesophageal
Junyuan Xiao1,2, Liang Cheng3, Tonglei Fang1
1Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China.
Abstract:
Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO2 with the endogenous H2 O2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber-covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced-stage oesophageal cancer.
Insights
Drug-eluting stents (DESs) loaded with oxygen-producing nanoparticles effectively treat esophageal cancer. This novel approach alleviates tumor hypoxia, enhancing photodynamic therapy (PDT) and prolonging survival in preclinical models.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Esophageal cancer presents a significant therapeutic challenge, often requiring innovative treatment strategies.
- Photodynamic therapy (PDT) is a promising cancer treatment, but its efficacy is limited by tumor hypoxia.
- Drug-eluting stents (DESs) offer a localized drug delivery platform, but their application in conjunction with PDT for esophageal cancer is underexplored.
Purpose of the Study:
- To develop and evaluate a novel drug-eluting stent (DES) system for enhancing photodynamic therapy (PDT) in esophageal cancer.
- To investigate the potential of oxygen-producing manganese dioxide nanoparticles embedded in electrospun fibers for alleviating tumor hypoxia.
- To assess the therapeutic efficacy and survival benefits of this DES-PDT system in preclinical models of esophageal cancer.
Main Methods:
- Electrospinning technology was employed to embed oxygen-producing manganese dioxide (MnO2) nanoparticles into fibers covering stents.
- The release and diffusion of MnO2 nanoparticles into tumor tissue were characterized.
- The ability of MnO2 to alleviate tumor hypoxia via reaction with endogenous hydrogen peroxide (H2O2) was investigated.
- PDT efficacy was evaluated in subcutaneous mouse tumor models and orthotopic rabbit esophageal cancer models.
Main Results:
- The developed stents successfully delivered MnO2 nanoparticles, which gradually released and diffused into tumor tissues.
- MnO2 nanoparticles effectively alleviated the hypoxic microenvironment within tumors by reacting with H2O2.
- The stent-based PDT demonstrated significant efficacy in both subcutaneous and orthotopic esophageal cancer models.
- Rabbits treated with intraluminal PDT using the fiber-covered stent exhibited greatly prolonged survival.
Conclusions:
- Fiber-covered stents serve as an effective nanoparticle delivery platform for enhancing PDT.
- This approach offers a promising noninvasive treatment strategy for advanced-stage esophageal cancer.
- The combination of DESs and oxygen-producing nanoparticles represents a significant advancement in PDT for solid tumors.
