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Layer‐by‐layer assembled PLGA nanoparticles carrying miR‐34a cargo inhibit the proliferation and cell cycle progression of triple‐negative breast cancer cells
Author(s) -
Kapadia Chintan H.,
Ioele Stephen A.,
Day Emily S.
Publication year - 2020
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36840
Subject(s) - triple negative breast cancer , cancer research , survivin , microrna , breast cancer , cell growth , cell , chemistry , cancer , medicine , gene , biochemistry
Abstract Triple‐negative breast cancer (TNBC) accounts for 15–25% of diagnosed breast cancers, and its lack of a clinically defined therapeutic target has caused patients to suffer from earlier relapse and higher mortality rates than patients with other breast cancer subtypes. MicroRNAs (miRNAs) are small non‐coding RNAs that regulate the expression of multiple genes through RNA interference to maintain normal tissue function. The tumor suppressor miR‐34a is downregulated in TNBC, and its loss‐of‐expression correlates with worse disease outcomes. Therefore, delivering miR‐34a mimics into TNBC cells is a promising strategy to combat disease progression. To achieve this goal, we synthesized layer‐by‐layer assembled nanoparticles (LbL NPs) comprised of spherical poly(lactic‐co‐glycolic acid) cores surrounded by alternating layers of poly‐L‐lysine (PLL) and miR‐34a. TNBC cells internalized these LbL NPs to a greater extent than polyplexes comprised of PLL and miRNA, and confocal microscopy showed that LbL NPs delivered a substantial fraction of miR‐34a cargo into the cytosol. This yielded robust suppression of the miR‐34a target genes CCND‐1, Notch‐1, Bcl‐2, Survivin, and MDR‐1, which reduced TNBC cell proliferation and induced cell cycle arrest. These data validate that miR‐34a delivery can impair TNBC cell function and support continued investigation of this platform for treatment of TNBC.