phytochlorin and stearic-acid

Currently, the development of polysaccharide, especially chitosan (CS), based drug delivery system to afford magnetic resonance imaging (MRI) guided theranostic cancer therapy remains largely unexplored. Herein, we successfully developed a CS derived polymer (Gd-CS-OA) through chemical conjugation of CS, octadecanoic acid (OA) and gadopentetic acid (GA). After self-assemble into glycolipid nanoparticles to loaded chlorin e6 (Ce6), the resulted Gd-CS-OA/Ce6 was able to realize MRI guided photodynamic therapy (PDT) of cancer. Our results revealed that Gd-CS-OA was able to increase the MRI sensitivity as compared to Gd-DTPA with decent residence time and preferable excretion behavior in vivo. Moreover, the Gd-CS-OA/Ce6 showed negligible hemolysis, satisfactory ROS generation and stability in physiological environments with preferable cellular uptake and enhanced in vitro cytotoxicity (through elevated ROS generation) on 4T1 cells. Most importantly, Gd-CS-OA/Ce6 demonstrated promising in vivo tumor targetability (enhanced penetration and retention effect) and powerful MRI guided tumor ablation through PDT on in situ 4T1 tumor model.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Chitosan; Chlorophyllides; Disease Models, Animal; Drug Delivery Systems; Female; Gadolinium DTPA; Glycolipids; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Nanoparticles; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents; Stearic Acids; Tumor Burden

Chlorines are attractive compounds for photodynamic therapy because of their high absorption in the red wavelength region. The stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles have been presented as potential candidates for intracellular drug delivery carrier because of their special structure. In this study, CSO-SA micelles were prepared to encapsulate chlorine e6 (Ce6). The physicochemical properties of synthesized CSO-SA micelles were characterized. The critical micelle concentration (CMC) of CSO-SA with 4.96% amino substituted degree (SD %) was about 36.27 +/- 1.51 microg/mL. The Ce6-loaded CSO-SA micelles were then prepared by a dialysis method, and the properties and drug release profiles of Ce6- loaded CSO-SA micelles (CSO-SA/Ce6) were investigated. The loading of Ce6 in the CSO-SA micelles could reach higher drug encapsulation efficiency (%), which was approximately 100%. The size of CSO-SA/Ce6 decreased after the loading of Ce6. The zeta potential of CSO-SA/Ce6 and the drug release rate decreased with the loading content of drug. After the Ce6 molecules were encapsulated into the micelles of CSO-SA, the cellular uptake percentage of Ce6 was much more than that of the free drug. And the cellular uptake percentage of CSO-SA/Ce6 micelles was increased with the incubation time in a short period.

Topics: Cells, Cultured; Chitosan; Chlorophyllides; Drug Delivery Systems; Humans; Micelles; Microscopy, Electron, Transmission; Oligosaccharides; Porphyrins; Solubility; Stearic Acids