Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer.

Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors.

Chemical and photonic interactions in vitro and in vivo between fluorescent tracer and nanoparticle-based scavenger for enhanced molecular imaging.

We hereby present a concept of scavenging excess imaging agent prior to a diagnostic imaging session, consequently allowing for enhanced contrast of signals originating from the tissue area of interest to the signals originating from systemic imaging agent residues. In our study, a prospective silica core-shell nanoparticle-based scavenger was designed and explored for its feasibility to scavenge a specific imaging agent (tracer) in the bloodstream. The developed tracer-scavenger system was first investigated under in vitro conditions to ensure proper binding between tracer and scavenger is taking place, as confirmed by Förster/fluorescence resonance energy transfer studies. In vivo, two-photon imaging was utilized to directly study the interaction of the scavenger particles and the tracer molecules in the vasculature of mice. To our knowledge, a methodological solution for in vivo differentiation between signals, originating from tissue and blood, has not been presented elsewhere.

Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation.

In this study, mesoporous silica nanoparticles (MSPs) of different size and shape were developed, and their surface coatings were utilized to study their differential effects in enhancing antibacterial activity. In brief, MSPs with three different aspect ratios (1, 2 and 4) were prepared, doped with silver ions and finally coated with the polymer chitosan. Both Gram-positive and Gram-negative bacteria were treated with the MSPs. Results indicate that silver ion doped and chitosan coated MSPs with the aspect ratio of 4 (Cht/MSP4:Ag+) have the highest antimicrobial activity among the prepared series. Further studies revealed that Cht/MSP4:Ag+ was most effective against Escherichia coli (E.coli) and least effective against Vibrio cholerae (V. cholerae). To investigate the detailed inhibition mechanism of the MSPs, the interaction of the nanoparticles with E.coli membranes and its intracellular DNA was assessed using various spectroscopic and imaging-based techniques. Furthermore, to increase the efficiency of the MSPs, a combinatorial antibacterial strategy was also explored, where nanoparticles, in combination with kanamycin (antibiotic), were used against Vibrio Cholerae (V. cholerae). Toxicity screening of these on MSPs was conducted on Caco-2 cells, and the results show that the dose used for antibacterial screening is below the limit of the toxicity threshold. Our findings show that both shape and surface engineering contribute positively towards killing bacteria, and the newly developed silver ion-doped and chitosan-coated MSPs have good potential as antimicrobial nanomaterials.