lactoferrin and Carcinoma--Ehrlich-Tumor

Quinacrine is an antimalarial drug that was repositioned for treatment of cancer. This is the first work to enhance quinacrine activity and minimize its associated hepatotoxicity via loading into bio-degradable, bio-renewable lignosulfonate nanoparticles. Particles were appraised for treatment of pancreatic cancer, one of the most life-threatening tumors with a five-year survival estimate. Optimum nanocomposites prepared by polyelectrolyte interaction exhibited a particle size of 138 nm, a negative surface charge (-28 mV) and a pH dependent release of the drug in an acidic environment. Ligands used for active targeting (lactoferrin and hyaluronic acid) were added to nanoparticles' surface via layer by layer coating technique. The highest anticancer activity on PANC-1 cells was demonstrated with dual active targeted particles (3-fold decrease in IC

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Movement; Cell Survival; Delayed-Action Preparations; Drug Liberation; Erythrocytes; Humans; Hyaluronic Acid; Lactoferrin; Lignin; Male; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Pancreatic Neoplasms; Quinacrine; Rabbits

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Cross-Linking Reagents; Drug Carriers; Female; Flavanones; Glutaral; Humans; Hydrophobic and Hydrophilic Interactions; Lactoferrin; MCF-7 Cells; Micelles; Nanoparticles; Scutellaria; Sirolimus; Zein

A comparative study of carrier-free 67Ga-citrate uptake by Ehrlich ascites tumor cells in the presence of lactoferrin, transferrin and ferritin has demonstrated that lactoferrin considerably increases the uptake of 67Ga, and that this increase seems to be determined by its iron-load. The other iron-binding proteins assayed have a null or negative effect. Their behavior in the presence of sodium citrate supports the concept of lactoferrin-binding by the cells as responsible for the uptake. The different behavior of 67Ga-citrate iron-binding protein complexes appears to support this hypothesis.

Topics: Animals; Carcinoma, Ehrlich Tumor; Citrates; Citric Acid; Ferritins; Gallium Radioisotopes; In Vitro Techniques; Lactoferrin; Lactoglobulins; Radionuclide Imaging; Transferrin

Tumor cells incubated with 67Ga-citrate plus lactoferrin showed a lactoferrin concentration-dependent increase of 67Ga uptake while for transferrin the effect was an inhibition. A correlation was observed between the binding of 131I-labelled lactoferrin or 131I-labelled transferrin and the uptake of 67Ga by the cells. Saturation with iron did not change significantly the effects of the iron-binding proteins. Preincubation with lactoferrin, transferrin or ferric citrate increased 67Ga uptake. The formation of a ternary complex in which 67Ga mimics iron is discussed.

Topics: Animals; Carcinoma, Ehrlich Tumor; Citrates; Citric Acid; Depression, Chemical; In Vitro Techniques; Lactoferrin; Lactoglobulins; Neoplasms, Experimental; Sarcoma, Experimental; Stimulation, Chemical; Transferrin