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- Title
Aptamer-Functionalized Nanoparticles Mediate PD-L1 siRNA Delivery for Effective Gene Silencing in Triple-Negative Breast Cancer Cells.
- Authors
Camorani, Simona; Tortorella, Silvia; Agnello, Lisa; Spanu, Chiara; d'Argenio, Annachiara; Nilo, Roberto; Zannetti, Antonella; Locatelli, Erica; Fedele, Monica; Comes Franchini, Mauro; Cerchia, Laura
- Abstract
Small interfering RNA (siRNA) therapies require effective delivery vehicles capable of carrying the siRNA cargo into target cells. To achieve tumor-targeting, a drug delivery system would have to incorporate ligands that specifically bind to receptors expressed on cancer cells to function as portals via receptor-mediated endocytosis. Cell-targeting and internalizing aptamers are the most suitable ligands for functionalization of drug-loaded nanocarriers. Here, we designed a novel aptamer-based platform for the active delivery of siRNA targeting programmed cell death-ligand 1 (PD-L1) to triple-negative breast cancer (TNBC) cells. The generated nanovectors consist of PLGA-based polymeric nanoparticles, which were loaded with PD-L1 siRNA and conjugated on their surface with a new RNA aptamer, specific for TNBC and resistant to nucleases. In vitro results demonstrated that these aptamer-conjugated nanoparticles promote siRNA uptake specifically into TNBC MDA-MB-231 and BT-549 target cells, along with its endosomal release, without recognizing non-TNBC BT-474 breast cancer cells. Their efficiency resulted in an almost complete suppression of PD-L1 expression as early as 90 min of cell treatment. This research provides a rational strategy for optimizing siRNA delivery systems for TNBC treatments.
- Subjects
APTAMERS; TRIPLE-negative breast cancer; GENE silencing; SMALL interfering RNA; PROGRAMMED death-ligand 1; DRUG delivery systems; CANCER cells; PROGRAMMED cell death 1 receptors
- Publication
Pharmaceutics, 2022, Vol 14, Issue 10, pN.PAG
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics14102225