期刊
PHARMACEUTICS
卷 14, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14102225
关键词
aptamer; PLGA-b-PEG nanoparticles; active siRNA delivery; PD-L1; endosomal escape; TNBC
资金
- Fondazione AIRC per la Ricerca sul Cancro [IG 23052]
- AIRC Fellowship
This study presents a novel aptamer-based platform for the targeted delivery of siRNA to triple-negative breast cancer cells. By utilizing cell-targeting and internalizing aptamers, this delivery system specifically delivers siRNA to TNBC cells, resulting in efficient suppression of PD-L1 expression.
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.
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