Studies Of Magnetic Resonance Visualized Theranostics Of Lung Cancer By Multifunctional Liposome

Early accurate diagnosis and realtime, safe and effective tumor detection is crucial in improvement of cure rate and life quality of the patient. The main concern is about the development of high level, precise and advanced diagnosis technologies. Imaging, especially the fast-growing molecular imaging, plays important roles in early tumor detection, active drug selecting, timely therapy evaluation and so forth. MRI (magnetic resonance imaging), one of most wildly used method to diagnose diseases, usually needs molecular imaging probes to improve the signal and image the targeted tumor site.Here, we developed a kind of multifunctional liposomal MRI probes, including T1 contrast agents and anti-cancer drugs. Further peptide modification could target to tumor in vivo. Active targeted drugs and contrast agents delivery could improve their efficiency and decrease the dose and off-target effects. Platinum-based drugs and paclitaxel are two established anticancer drugs. When used together, they constitute an effective strategy for treating advanced non-small-cell lung cancer (NSCLC). To give full play of these drugs, dual drug-loaded liposome functionalized with non-invasive multimodality imaging contrast agents, can provide both good tumor diagnosis and inhibition and monitoring of the disease treatment. Lipid film and hydration method was used to prepare paclitaxel liposome. This nanoparticle overcame the insolubility of paclitaxel, reduced the side effects of FDA-approved formulation of PTX-Cre (Taxol(?)) and improved the drug delivery efficiency to the tumor. Gd-DOTA encapsoluted in the liposome can enhance the MRI signal and give a bright image. Liposome can target to tumor cell by further c(RGDyk) modification, improving the drug and contrast agent efficiency. This targeted liposome greatly enhanced the cytotoxicity of the drug to tumor cells A549 by in vitro MTT studies. The T1 relaxivity in tumor cells treated with the targeted liposome formulation was increased 16-fold when compared with the non-targeted group. In vivo, the tumors in mice were clearly visualized using Ti-weighted imaging after administration of the liposome. Fluorescence images in vitro and ex vivo also showed the targeted effect of this liposome in tumor cells, indicating that this nanovehicle could limit the off-target side effects of anticancer drugs and contrast agents. These findings lay the foundations for the further tumor inhibition studies and application of this delivery vehicle in cancer therapy settings.Based on the foregoing studies, a theranostic dual drug-loaded liposomal drug delivery system was developed, which integrate multimodality targeted imaging and doublet chemotherapy drug delivery. Targeted paclitaxel and carboplatin combinations showed apparent synergic cytotoxicity on non-small-cell lung cancer cells A549 and H1299. The toxicity on normal cell WI-38 was little. The T1-weighted MRI signal of lung cancer tumor was much stronger after administration of the multifunctional liposome when compared to the contrast agent Omniscan(?) at the same dose. The diagnostic and drug therapy time was also greatly prolonged. Furthermore, the tumor therapy could be monitored non-invasively by MRI in realtime, demonstrating the good performance of the doublet chemotherapy drug delivery liposome on tumor growth inhibition. Small volumm tumor (1 mm3) could also be detected by MRI, indicating high effciciency of this nanoparticle. The characters of nanoparticles and the targeted effect of peptide c(RGDyK) can decrease the dose of the drug and contrast agent greatly, realizing the safe application in animal studies. Drugs combinations can aslo decrease the dose and the drug resistance. These results showed the potential and superiority of this liposomal nanoparticle in developing theranostic drug delivery system. By the studies in vitro and in vivo, this targeted drug-loaded liposomal system, have good biocompatibility, can successfully carry both hydrophobic and hydrophilic molecules and be detected by multimodality imaging technologies. Importantly, non-invasive and real-time diagnosis and monitoring of disease development and therapeutic responses by MRI allows for the treatment strategy adjustment, which has great implications for personalized cancer therapy. This delivery sytem can also be used as an excellent theranostic agent and a promising platform for studying and treating other solid tumors.