Mesoporous silica coated SPIONs containing curcumin and silymarin intended for breast cancer therapy.

INTRODUCTION: Super-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2@SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7. METHODS: Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy. RESULTS: The MTT results showed that the IC50 of CUR + SIL loaded mSiO2@SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis. CONCLUSION: In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.

Pegylated magnetic mesoporous silica nanoparticles decorated with AS1411 Aptamer as a targeting delivery system for cytotoxic agents.

Fulfilling the purpose of developing a NP with theragnostic capabilities, the current study describes the synthesis of an aptamer-functionalized PEG-coated SPION/mesoporous silica core-shell nanoparticle for concurrent cancer targeted therapy and magnetic resonance imaging. SPIONs were synthesized according to a thermal decomposition method and served as cores for SPION/mesoporous silica core/shell nanoparticles (MMSNs). Doxorubicin was then successfully loaded in MMSNs which were then coated with di-carboxylic acid functionalized polyethylene glycol (PEG-MMSNs). AS1411 aptamers were at the end covalently attached to NPs (APT-PEG-MMSNs). The mean diameter of synthesized NPs was about 89 nm and doxorubicin encapsulation efficacy was ≈67.47%. Results of MTT based cell cytotoxicity assay demonstrated a significantly higher toxicity profile for APT-PEG-MMSNs against MCF7 cells compared to non-decorated MMSNs, while no significant differences were spotted against NIH-3T3 cells. Meanwhile, formation of protein corona around APT-PEG-MMSNs in biological medium significantly attenuated observed cytotoxicity against MCF7 cell line. Examining NPs uptake by MCF7 cells using confocal laser scanning microscopy also confirmed superiority of APT-PEG-MMSNs over PEG-MMSNs. Finally, APT decorated NPs induced highest signal intensity reduction in T2-weighted images during in vitro MRI assay. In conclusion, developed NPs may serve as promising multifunctional vehicles for simultaneous cancer targeted therapy and MRI imaging.

Protein corona change the drug release profile of nanocarriers: the "overlooked" factor at the nanobio interface.

The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane®, albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo.

Exocytosis of nanoparticles from cells: role in cellular retention and toxicity.

Over the past decade, nanoparticles (NPs) have been increasingly developed in various biomedical applications such as cell tracking, biosensing, contrast imaging, targeted drug delivery, and tissue engineering. Their versatility in design and function has made them an attractive, alternative choice in many biological and biomedical applications. Cellular responses to NPs, their uptake, and adverse biological effects caused by NPs are rapidly-growing research niches. However, NP excretion and its underlying mechanisms and cell signaling pathways are yet elusive. In this review, we present an overview of how NPs are handled intracellularly and how they are excreted from cells following the uptake. We also discuss how exocytosis of nanomaterials impacts both the therapeutic delivery of nanoscale objects and their nanotoxicology.

Effect of Erythropoietin on Serum Brain-derived Biomarkers after Carbon Monoxide Poisoning in Rats.

OBJECTIVES: Erythropoietin has been shown to exert neuroprotective effects in a variety of CNS injury models. Elevation of serum S100ß, as a glial damage marker and myelin basic protein (MBP) has been reported to occur in acute carbon monoxide (CO) poisoning. The aim of this study was to evaluate the effect of erythropoietin (EPO) on serum S100ß and MBP levels after CO poisoning in rats. MATERIALS AND METHODS: Rats were poisoned with a mixture of 3000 PPM CO in air for 65 min. After exposure, half of the rats received 5000 u/kg EPO and the rest received normal saline. At 3, 6, 12, 24, 48, 72, 144, and 336 hr after exposure samples were taken. Additionally, EPO was administered at three lower doses (625, 1250 and 2500 u/kg). The serum S100ß and MBP levels were measured using immunoenzymatic colorimetric assay. Hemoglobin level was alsomeasured. RESULTS: Serum S100ß levels in CO poisoned rats were significantly higher compared to the control group [6 hr (P< 0.01), 12 hr (P< 0. 001), 24 hr (P< 0.001), 48 hr (P< 0.008) and 72 hr (P< 0.008)]. EPO administration could significantly prevent serum S100ß elevations after 12 hr (P< 0.008) and 24 hr (P< 0.008) of CO poisoning. Serum MBP levels in CO poisoned rats were not significantly increased in comparison with the control group (P> 0.05). EPO significantly increased the hemoglobin levels. CONCLUSION: EPO could partially prevent neuronal damage. More studies are required to elucidate other aspects of these effects.

Polyanionic carbohydrate doxorubicin-dextran nanocomplex as a delivery system for anticancer drugs: in vitro analysis and evaluations.

This study deals with the preparation and investigation of a nanoscale delivery system for the anticancer drug doxorubicin (DOX) using its complexation with polyanionic carbohydrate dextran sulfate (DS). Dynamic light scattering, SEM, and zeta potential determination were used to characterize nanocomplexes. DOX-DS complexation was studied in the presence of ethanol as a hydrogen-bond disrupting agent, NaCl as an electrostatic shielding agent, and chitosan as a positively charged polymer. Thermodynamics of DOX-DS interaction was studied using isothermal titration calorimetry (ITC). A dialysis method was applied to investigate the release profile of DOX from DOX-DS nanocomplexes. Spherical and smooth-surfaced DOX-DS nanocomplexes (250-500 nm) with negative zeta potential were formed at a DS/DOX (w/w) ratio of 0.4-0.6, with over 90% drug encapsulation efficiency. DOX when complexed with DS showed lower fluorescence emission and 480 nm absorbance plus a 15 nm bathometric shift in its visible absorbance spectrum. Electrostatic hydrogen bonding and π-π stacking interactions are the main contributing interactions in DOX-DS complexation. Thermal analysis of DOX-DS complexation by ITC revealed that each DOX molecule binds with 3 DS glycosyl monomers. Drug release profile of nanocomplexes showed a fast DOX release followed by a slow sustained release, leading to release of 32% of entrapped DOX within 15 days. DOX-DS nanocomplexes may serve as a drug delivery system with efficient drug encapsulation and also may be taken into consideration in designing DOX controlled-release systems.