Abstract
Nanoparticles have revolutionized medical research over the last decade. One notable emerging area of nanomedicine is research developments in the reproductive sciences. Since increasing evidence indicates links between abnormal gene expression and previously unexplained states of infertility, there is a strong impetus to develop tools, such as nanoparticle platforms, to elucidate the pathophysiological mechanisms underlying such states. Mesoporous silica nanoparticles (MSNPs) represent a powerful and safe delivery tool for molecular and genetic investigations. Nevertheless, ongoing progress is restricted by low efficiency and unpredictable control of cargo delivery. Here, we describe for the first time, the development of a laser-activated MSNP system with heat-responsive cargo. Data derived from human embryonic kidney cells (HEK293T) indicate that when driven by a heat-shock promoter, MSNP cargo exhibits a significantly increased expression following infrared laser stimulus to stimulate a heat-shock response, without adverse cytotoxic effects. This delivery platform, with increased efficiency and the ability to impart spatial and temporal control, is highly useful for molecular and genetic investigations. We envision that this straightforward stimuli-responsive system could play a significant role in developing efficient nanodevices for research applications, for example in reproductive medicine.
Highlights
Nanoparticles represent an efficient and inexpensive delivery platform for molecular research and medicine, which can directly target physiological pathways in a noninvasive manner to mark, augment, or suppress endogenous functional activity
A thermo-controlled plasmid was successfully created to act as a nanoparticle cargo by fusing the human HSP70 promoter to the green fluorescent protein (GFP) reporter gene (HSP:GFP) (Fig. 1)
The large variance in intensity measurements indicated that not all cells internalized the same amount of mesoporous silica nanoparticles (MSNPs) and that different-sized nanoparticle agglomerates were being formed
Summary
Nanoparticles represent an efficient and inexpensive delivery platform for molecular research and medicine, which can directly target physiological pathways in a noninvasive manner to mark, augment, or suppress endogenous functional activity. Mesoporous silica nanoparticles (MSNPs) are universally recognized as a powerful biomedical nanomaterial distinguished for low cytotoxicity across a variety of cell types.[1] MSNPs are synthetically modified colloidal silica with highly ordered meso-sized pores (2 to 50 nm)[2] and exhibit a suite of favorable characteristics for use as a targeted delivery vector for reproductive biology These characteristics include high surface-area-to-volume ratio, high loading capacity, both mechanical and thermal stability, and resistance to fluctuations in pH.[3] Their small size, similar to that of biomolecules, allows for simple integration into physiological cellular processes, such as internalization via endocytosis or selective targeting of endogenous functional pathways.[4,5] Notably, by manipulating numerous physical and chemical properties such as size, surface charge, polarity, and functional group/ligand attachments, they can be tailored to facilitate cargo loading and target tissue specificity.[6,7]
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