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.

SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against metastatic colon cancer cells.

Combination of chemotherapy and photothermal therapy has been proposed for better treatment of metastatic colon cancer. In this study SN38, a highly potent cytotoxic agent, was conjugated to negatively charged hyaluronic acid (HA), which was deposited on the surface of the positively charged gold nanoparticles via electrostatic interaction. The drug conjugation and its interaction with gold nanoparticles were verified by 1H NMR and UV-vis spectroscopies, respectively. The prepared SN38-HA gold NPs are negatively charged spherical nanoparticles with an average size of 75±10nm. In vitro release study revealed that drug release in acidic conditions (pH 5.2) was faster than that in physiological pH. Red light emitting diode (LED, 630nm, 30mW) was used as a light source for photothermal experiments. The drug release in acidic conditions was increased up to 30% using red LED illumination (6min) in comparison with experiment carried out indark. The cytotoxicity study on MUC1 positive HT29, SW480 colon cancer cells and MUC1 negative CHO cells, showed higher toxicity of the nanoparticles on HT29 and SW480 cell lines compared to CHO cells. Confocal microscopy images along with flow cytometry analysis confirm the cytotoxicity results. The incubation time for reaching IC50 decreases from 48h to 24h by LED illumination after nanoparticle treatment. Migratory potential of the HT29 and SW480 cell lines was reduced by co-application of SN38-HA gold NPs and LED radiation. Also anti-proliferative study indicates that LED radiation has increased the cytotoxicity of the nanoparticles and this effect is remained up to 8days.

Protein corona hampers targeting potential of MUC1 aptamer functionalized SN-38 core-shell nanoparticles.

Nanoparticles have been considered to improve delivery and physicochemical characteristics of bioactive agents in recent years. In this study, a core-shell chitosan nanoparticulate system was prepared for the targeted delivery of SN-38. SN-38, an active metabolite of camptothecin, conjugated to hyaluronic acid (HA) was used as the shell of chitosan nanoparticles decorated with MUC1 aptamer. The conjugation was confirmed by UV and (1)H NMR techniques. Targeting efficiency was evaluated by confocal microscopy and flow cytometry. It was shown that MUC1 decoration increased the uptake of nanoparticles by HT29 cells, MUC1 positive cell line, while CHO as MUC1 negative cell line showed no enhanced uptake of decorated nanoparticles. Compared to non-targeted nanoparticles, flow cytometric annexin V/PI analyses showed that the nanoparticles exert cytotoxicity through apoptosis. It was, however, shown that protein corona adsorption at the surface of nanoparticles hampered the cytotoxicity of nanoparticles, as there was no difference between the cytotoxicity of targeted and non-targeted nanoparticles, when treated with bovine serum albumin prior to cytotoxicity study.

Chitosan-Pluronic nanoparticles as oral delivery of anticancer gemcitabine: preparation and in vitro study.

Nanoparticles have proven to be an effective delivery system with few side effects for anticancer drugs. In this study, gemcitabine-loaded nanoparticles have been prepared by an ionic gelation method using chitosan and Pluronic(®) F-127 as a carrier. Prepared nanoparticles were characterized using dynamic light scattering, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy, and transmission electron microscopy. Different parameters such as concentration of sodium tripolyphosphate, chitosan, Pluronic, and drug on the properties of the prepared nanoparticles were evaluated. In vitro drug release was studied in phosphate-buffered saline (PBS; pH = 7.4). The cytotoxicity of the nanoparticles was assayed in the HT-29 colon cancer cell line. The mucoadhesion behavior of the nanoparticles was also studied by mucus glycoprotein assay. The prepared nanoparticles had a spherical shape with positive charge and a mean diameter ranging between 80 to 170 nm. FT-IR and DSC studies found that the drug was dispersed in its amorphous form due to its potent interaction with nanoparticle matrix. Maximum drug encapsulation efficiency was achieved at 0.4 mg/mL gemcitabine while maximum drug loading was 6% obtained from 0.6 mg/mL gemcitabine. An in vitro drug release study at 37°C in PBS (pH = 7.4) exhibited a controlled release profile for chitosan-Pluronic(®) F-127 nanoparticles. A cytotoxicity assay of gemcitabine-loaded nanoparticles showed an increase in the cytotoxicity of gemcitabine embedded in the nanoparticles in comparison with drug alone. The mucoadhesion study results suggest that nanoparticles could be considered as an efficient oral formulation for colon cancer treatment.