Fig. 1.

Complex cancer targeted drug delivery system. A, Schema of the delivery system containing poly(propylenimine) (PPI) dendrimer as a carrier; paclitaxel (TAX) as an anticancer drug, conjugated to the dendrimer via succinic acid (SA) spacer; luteinizing-hormone-releasing hormone (LHRH) as a cancer cell targeting moiety, conjugated to the dendrimer via poly(ethylene glycol) (PEG) spacer; siRNA targeted to CD44 mRNA and caged by Dimethyl 3,3′-dithio-bis(propionimidate) dihydrochloride (DTBP). B, Representative image of matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry analysis of PPI-TAX conjugate. The most abundant peak [M+Na] was observed at mass M=8,122 indicating that paclitaxel was conjugated with the PPI dendrimer (M=7162). C, Representative gel electrophoresis image of siRNA complexated with PPI dendrimer at different nitrogen to phosphate (N/P). The complexes were synthesized with 0.4 μM siRNA and 126 μM ethidium bromide. The concentration of PPI dendrimer was increased in order to obtain N/P ratios from 0 (no PPI dendrimer) to 3. The nanoparticles with N/P ratio equal to 2.4 were used in all studies. D, Atomic force microscope (AFM) images of nanoparticles resulted from the complex formation between the carrier and siRNA and quantitative analysis of the stability of naked siRNA and siRNA-PPI complexes in plasma.