Aptamer-Functionalized Nanoparticles Mediate PD-L1 siRNA Delivery for Effective Gene Silencing in Triple-Negative Breast Cancer Cells

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...

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Bibliographic Details
Published in:Pharmaceutics 2022-10, Vol.14 (10), p.2225
Main 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
Format: Article
Language:English
Subjects:
active siRNA delivery
Analysis
Apoptosis
aptamer
Breast cancer
Cancer cells
Chemotherapy
Drug delivery systems
Drugs
endosomal escape
Genetic engineering
Health aspects
Ligands
Metastasis
Methods
Nanoparticles
PD-L1
PLGA-b-PEG nanoparticles
TNBC
Tumors
Vehicles
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14102225