Construction of aptamer-siRNA chimera and glutamine modified carboxymethyl-β-cyclodextrin nanoparticles for the combination therapy against lung squamous cell carcinoma - 27/04/24
Abstract |
Combination therapy has become the most important treatment for advanced non-small cell lung cancer (NSCLC), which can significantly improve the prognosis of patients. However, poor targeting and adverse reactions limited its clinical application. Here, we constructed an AS1411 aptamer-programmed cell death ligand-1 (PD-L1) siRNA chimera/polyethylenimine/glutamine/β-cyclodextrin/doxorubicin (Chimera/ PEI/Gln/β-CD/DOX) nanoparticle for the combination therapy (chemotherapy combined with immunotherapy). Scanning electron microscopy showed that PEI/Gln/β-CD/DOX nanoparticle was conical, with a diameter of about 250–500 nm. AS1411 aptamer-PD-L1 siRNA chimera can effectively bind NSCLC cells and inhibit PD-L1 expression, further activating T cells and CD8+T cells. Glutamine modification effectively promoted the doxorubicin uptake by cancer cells and induced their apoptosis. Animal experiments showed that our nanoparticles effectively treated the transplanted tumor, and the adverse reactions were reduced. Compared with the Aptamer/β-CD/DOX group, the volume and ki-67 index of transplanted tumors in the Chimera/β-CD/DOX group were significantly decreased, while the apoptosis ratio was increased. Immunohistochemical results showed that Compared with the Aptamer/β-CD/DOX group, the number of T cells and CD8+T cells in the Chimera/β-CD/DOX group was increased by 1.34 and 1.41 times. Glutamine modification enhanced the chemotherapeutic efficacy and anti-tumor immune response in vivo. Our study provided a new method for the combination therapy of lung squamous cell carcinoma.
El texto completo de este artículo está disponible en PDF.Graphical Abstract |
Highlights |
• | Aptamer-siRNA chimera achieves specific binding and target gene silencing. |
• | Glutamine modification enhances the phagocytosis of nanoparticles. |
• | Chimera/PEI/Gln/β-CD/DOX nanoparticles can be used for the comprehensive treatment of lung squamous cell carcinoma. |
Abbreviations : PD-L1, PEI, Gln, β-CD, DOX, NSCLC, CRS, EDC, NHS, DMSO, FAM, PBS, MTT, TUNEL
Keywords : lung squamous cell carcinoma, aptamer, glutamine, chemotherapy, immunotherapy
Esquema
Vol 174
Artículo 116506- mai 2024 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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