Osteoporosis
is the most common disease involving bone degeneration.
Current clinical treatments are not able to offer a satisfying curative
effect, so the development of effective treatments is desired. Gene
silencing through siRNA delivery has gained great attention as a potential
treatment in bone diseases. SOST gene inhibits the Wnt signaling pathway
reducing osteoblast differentiation. Consequently, silencing SOST
genes with a specific siRNA could be a potential option to treat osteoporosis.
Generally, siRNAs have a very short half-life and poor transfection
capacity, so an effective carrier is needed. In particular, mesoporous
silica nanoparticles (MSNs) have attracted great attention for intracellular
delivery of nucleic acids. We took advantage of their high loading
capacity to further load the pores with osteostatin, an osteogenic
peptide. In this study, we developed a system based on MSNs coated
with poly(ethylenimine), which can effectively deliver SOST siRNA
and osteostatin inside cells, with the consequent augmentation of
osteogenic markers with a synergistic effect. This established the
potential utility of MSNs to co-deliver both biomolecules to promote
bone formation, this being a potential alternative to treat osteoporosis.
Nanotechnology changed the concept of treatment for a variety of diseases, producing a huge impact regarding drug and gene delivery. Among the different targeted diseases, osteoporosis has devastating clinical and economic consequences. Since current osteoporosis treatments present several side effects, new treatment approaches are needed. Recently, the application of small interfering RNA (siRNA) has become a promising alternative. Wnt/β‐catenin signaling pathway controls bone development and formation. This pathway is negatively regulated by sclerostin, which knock‐down through siRNA application would potentially promote bone formation. However, the major bottleneck for siRNA‐based treatments is the necessity of a delivery vector, bringing nanotechnology as a potential solution. Among the available nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of siRNAs. The mesoporous structure of MSNs permits the delivery of siRNAs together with another biomolecule, achieving a combination therapy. Here, the effectiveness of a new potential osteoporosis treatment based on MSNs is evaluated. The proposed system is effective in delivering SOST siRNA and osteostatin through systemic injection to bone tissue. The nanoparticle administration produced an increase expression of osteogenic related genes improving the bone microarchitecture. The treated osteoporotic mice recovered values of a healthy situation approaching to osteoporosis remission.
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.
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