Abstract
Pharmacological RelevancePaclitaxel (PTX) is currently the only botanical drug that can control the growth of cancer cells. Paclitaxel is widely used in the treatment of breast cancer, ovarian cancer, uterine cancer, non-small cell lung cancer and other cancers.AimFolate receptor and integrin αvβ3 are highly expressed on the surface of human breast cancer cells MCF-7. Folic acid and arginine-glycine-aspartate (Arg-Gly-Asp, RGD) tripeptide sequence have a high affinity for folate receptor and integrin αvβ3, respectively. To enhance the effect on breast cancer, we constructed the folate acid and RGD peptide dual-targeted (MSNs-NH2-FA-RGD) drug-carrier based on mesoporous silica nanoparticles.MethodsThe structure of mesoporous nanocarriers was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy, laser particle size analyzer, and thermogravimetric analysis. Paclitaxel was chosen as the model drug. The targeting-ability was verified by observing the uptake of mesoporous carriers loaded with rhodamine in MCF-7, MCF-10A, and HeLa cells using a fluorescence microscope. The cytotoxicity of the blank carrier MSNs-NH2-FA-RGD and the efficacy of the drug carrier PTX@MSNs-NH2-FA-RGD were assessed by cell experiments.ResultsThe characterization showed successful construction of a dual-targeted mesoporous silica nanocarrier. Obvious differences were detected in the fluorescence intensity of the three cell lines. The results of the pharmacological tests indicated that the blank nanoparticles do not cause any apparent toxicity on these cells. The IC50 of free PTX and PTX@MSNs-NH2-FA-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX.ConclusionsThe dual-targeted nanocarrier MSNs-NH2-FA-RGD could target breast cancer cells, and sever as a potential candidate in future of drug development.
Highlights
The IC50 of free PTX and PTX@Mesoporous silica nanoparticles (MSNs)-NH2-Folic acid (FA)-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX
transmission electron microscopy (TEM) images showed that the MSNs and MSNs-NH2-FA-RGD nanoparticles were spherical, with smooth surface and even distribution (Figures 2A, B)
Due to the PEG long chains on the targeted group covering the positive charge of MSNs-NH2, the positive potential of MSNs-NH2-FA, and MSNs-NH2-FA-RGD have decreased to 24.4 ± 7.36 mV and 22.9 ± 3.9 mV, respectively (Figure 2D)
Summary
Statistics show that 1.2 million women worldwide suffer from breast cancer each year, and 500,000 women die from breast cancer (Raviv, 2004). The patient population has shown a trend of being younger. Traditional chemotherapy exposes many issues, such as poor specificity by chemotherapeutics, drug resistance caused by repeated and large doses of multi-drugs, and side effects to normal tissues. The treatment has received widespread attention in the medical community. Many researchers have put a lot of effort into targeted treatment field. With in-depth research, nanocarriers are found to play an increasingly important role in targeted therapy. Owing to passive or active targeted delivery of drugs, the nanocarriers have shown great potential in improving drug concentration and bioavailability in tumor sites (Darvishi and Farahmand, 2017)
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