Open AccessIntravaginal poly-(D, L-lactic-co-glycolic acid)-(polyethylene glycol) drug-delivery nanoparticles induce pro-inflammatory responses with Candida albicans infection in a mouse model
Author(s) -
Taslima T. Lina,
Shemedia J. Johnson,
R. Doug Wagner
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0240789
Subject(s) - candida albicans , apoptosis , corpus albicans , dna laddering , oxidative stress , microbiology and biotechnology , biology , chemistry , programmed cell death , biochemistry , dna fragmentation
In a recent study, using an in vitro model to study intravaginal nanoparticle exposure during yeast infections, we demonstrated that C . albicans exposure suppressed apoptotic gene expression and induced oxidative stress and pyroptosis in vaginal epithelial cells. The mucous-penetrating drug delivery nanoparticles made from poly-(D, L-lactic- co -glycolic acid)-(polyethylene glycol) induced cytotoxicity by activating apoptosis, endoplasmic reticulum (ER) stress, oxidative stress, and DNA damage repair responses alone and, in some cases with C . albicans . In the current study we evaluated the effects of fluorescently-labelled nanoparticles in CBA/J mice challenged intravaginally for two hours followed by intravaginal challenge with C . albicans for 18 hours. Nanoparticle treatment increased systemic translocation of C . albicans threefold in the heart. C . albicans also increased systemic distribution of the nanoparticles fivefold in the heart. Flow cytometric assays showed co-localization of the nanoparticles with epithelial cells, macrophages and dendritic cells. Nanoparticle-treated, C . albicans -infected mice exhibited induction of autophagy, ER stress, apoptosis, and inflammatory serum cytokines. C . albicans infection was associated with pyroptosis and suppressed expression of ER stress and apoptosis-related genes. Induction of apoptosis during nanoparticle treatment and in nanoparticle-treated- C . albicans infected mice was observed as DNA damage responses, mitochondrial depolarization and (Poly [ADP-Ribose] Polymerase) cleavage. C . albicans infection was associated with increased mRNA expression of anti-apoptotic genes. Both C . albicans infection and nanoparticle treatment showed enhanced chemoattraction of dendritic cells and polymorphonuclear cells to factors in vaginal washings in a chemotaxis assay. This study shows that both intravaginal treatment of mice with the nanoparticles and infection with C . albicans induce cytotoxic and inflammatory responses. C . albicans also suppressed cell apoptosis. These results clarify our understanding of how nanoparticles modulate host cellular responses during C . albicans infection and will be applicable for future research and development of intravaginal nanomedicines.