Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Cancer Treatment and Fertility

Abstract

Throughout the female menstrual cycle, physiological changes occur that affect the biodistribution of nanoparticles within the reproductive system. We demonstrate a 2-fold increase in nanoparticle accumulation in murine ovaries and uterus during ovulation, compared to the nonovulatory stage, following intravenous administration. This biodistribution pattern had positive or negative effects when drug-loaded nanoparticles, sized 100 nm or smaller, were used to treat different cancers. For example, treating ovarian cancer with nanomedicines during mouse ovulation resulted in higher drug accumulation in the ovaries, improving therapeutic efficacy. Conversely, treating breast cancer during ovulation, led to reduced therapeutic efficacy, due to enhanced nanoparticle accumulation in the reproductive system rather than at the tumor site. Moreover, chemotherapeutic nanoparticles administered during ovulation increased ovarian toxicity and decreased fertility compared to the free drug. The menstrual cycle should be accounted for when designing and implementing nanomedicines for females.

The Fate of Intranasally Instilled Silver Nanoarchitectures

“…57 This is relevant when considering gender-specific toxicity, treatment performances, and effects on the reproductive system. 58 The content of silver found in the testes 24 h from IN administration was 0.007%ID with a decreasing trend over time (Figure 2e). Hence, the possibility of reproductive toxicity after AgNAs IN exposure may be negligible.…”

“…Remarkably, silver biodistribution may be gender related . This is relevant when considering gender-specific toxicity, treatment performances, and effects on the reproductive system . The content of silver found in the testes 24 h from IN administration was 0.007%ID with a decreasing trend over time (Figure e).…”

Sex‐Based Differences in the Biodistribution of Nanoparticles and Their Effect on Hormonal, Immune, and Metabolic Function

“…This resulted in a twofold increase in nanoparticles' accumulation in mice ovaries and a 2.5-fold increase in the uterus. [16] For males, changes in the hormonal profile such as lowered testosterone levels during later life may lead to erectile dysfunction and infertility. [107] Males that suffer from this condition are treated with hormonal therapies or medications, such as sildenafil, [108] which may affect nanoparticle distribution; [109] however, this aspect has not been studied yet.…”

The Impact of Metal Nanoparticles on Female Reproductive System: Risks and Opportunities

“…Both male and female reproductive organs are vulnerable, but in females the presence of NPs may compromise fertility and eventual fetal development more dramatically due to the fixed and not renewable number of oocytes present at birth in the mammalian ovaries. Furthermore, NP accumulation seems to be strongly conditioned by menstrual cycle, as demonstrated by the 2- fold increase in ovarian and uterine NP content occurring during mouse ovulation in comparison with the other stages of estrus cycle [ 60 ]. In this review we will discuss not only of the toxic effects of selected NPs on female reproductive organs but also of their importance for fertility preservation.…”