Theragnostic Drug Delivery System Design of Radiolabeled Docetaxel Loaded Magnetic Lipid Nanoparticles and In Vivo Tumor Imaging

Project no. 20402 · Status: Kapanmış (Yayın bekleniyor) · 2019

Summary

Theranostics approaches have an important place, advanced treatment and diagnostic techniques, in the development and personalized medicine. Nanoparticle systems perform the cancer theranostics by carrying a wide variety of chemotherapeutic and diagnostic agents to tumor cells. Last two decade’s nanoparticle delivery systems has attracted great attention in order to overcome the low therapeutic effect of conventional anticancer drugs. The selected drug delivery system has great importance in this approach. In recent years with this aim liposomes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and other molecules such as polymers, have been developed as drug delivery systems and investigated in vivo / in vitro. In numerous preclinical studies, focuses on the development of formulations to be carried taxanes, clinically the most commonly used and which is one of the most important anticancer drugs, effectively. When considering the hydrophobicity of taxanes lipid-based nanoparticles have suitable properties as an alternative carrier system.In this study, a radiolabeled solid lipid nanoparticle system was developed by loading superparamagnetic iron oxide nanoparticles (SLMNP) with docetaxel (DTX), an anticancer drug from the taxane family, as a drug delivery system that will function both in cancer treatment and diagnosis.For this purpose, firstly, SLMNP was synthesized by hot homogenization method and the surface of the particles was modified with a folate derivative to transport them to tissues with folate receptors.Structural characteristics of these nanoparticles were determined by Dynamic Light Scattering (DLS) method, Zeta Potential Analysis, Scanning Electron Microscope (SEM) and transmission electron microscope (TEM) images. The synthesized magnetic solid lipid nanoparticles were loaded with DTX and then radiolabeling was carried out with technetium-99m.The zeta potential surface charge of the synthesized SLMNP was -34.4 mV, and the DTX-SLMNP of the drug-loaded particles was -20.8 mV. The DLS results of MNP, SLMNP and DTX-SLMNP were measured at 189.1nm, 328.6nm and 317.3nm, respectively. SEM images of MNPs are in the range of 40-70 nm and have a round morphology. According to TEM images of MNP, SLN and SLMNP nanoparticles, MNPs were observed between 25-35 nm, SLNs between 400-500 nm and SLMNPs between 350-450 nm. The drug entrapment efficiency of SLMNPs loaded with DTX was found to be 19% and drug release was found to be 12% in pH 7 phosphate buffer medium for 6 hours.For DTX-SLMNP radiolabelled with 99mTc, the percentage efficiency of radiolabeling was found as 98.0±2.0 %.The biological behavior of this radiolabeled system was investigated in vitro and in vivo.Folate receptor positive SKOV-3 and folate receptor negative A549 cancer cell lines were studied to investigate the cellular level activities of 99mTc-labeled DTX-loaded folate receptor-targeted solid lipid magnetic nanoparticles (99mTc-DTX-SLMNP). The IC50 values of DTX-SLMNP in SKOV-3 and A549 cells at 24 hours were 126.2 µM and 232.23 µM, respectively, and 50.21 µM and 172.27 µM at 48 hours, respectively.99mTc-DTX-SLMNP and 99mTc-MA-DTX-SLMNP had the highest binding efficiency in both cell lines at the 240th minute, but the binding efficiency in the cell was higher when external magnetic field was applied.The biological behaviors of 99mTc-DTX-SLMNP and magnetically applied 99mTc-DTX-SLMNP compounds were determined in vivo from gamma camera imaging studies on SKOV3 and A549 cells and tumor-formed CD-1 Nude mice.It was understood that the uptake in the tumor region formed by SKOV-3 cell lines was higher than the uptake in the tumor region formed by A549 cell lines.It is thought that the optimized drug delivery system we prepared in this project can be evaluated for preclinical studies of new drug carrier formulations of taxane class of anticancer drugs.Key Words: theranostic; radiolabelled nanoparticles; molecular imaging; taxane

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