Abstract
In this paper, to achieve the targeted ability of anti-tumor drug doxorubicin (DOX), enhance the treatment effect and reduce the side effect, a novel pH-sensitive and charge-convertible prodrug nanogel was prepared. Firstly, cis-aconitic anhydride-doxorubicin prodrug (CAD) and Pluronic F127-chitosan-CAD (F127-CS-CAD) conjugates were synthesized. Then the DOX loaded polyion complex micelles (F127-CS-CAD/CAD) were prepared by self-assembling, thus CAD was incorporated into micelles via electrostatic interactions between electronegative CAD and positively charged F127-CS-CAD and hydrophobic interactions. Finally a pH-responsive charge-convertible copolymer, folic acid modified gelatin (Gel-FA) was shielded on the surface of micelles and the Gel-FA/F127-CS-CAD/CAD nanogel was formed, the charge-convertible capability was evaluated through changes of the morphology and Zeta potential under different pH value environment by transmission electron microscopy (TEM) and Zeta potential analyzer. And in vitro pH-dependent and two-phase drug release from nanogel was also evaluated. In vitro anti-tumor activity of Gel-FA/F127-CS-CAD/CAD nanogel was performed on HeLa cells and HepG2 cells to prove the strong cell toxicity of nanogels. Finally, the in vivo safety experiments showed that the nanogel achieved the reducing the toxic side effects of DOX significantly.
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