Novel water-soluble and pH-responsive anticancer drug nanocarriers: Doxorubicin–PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs)

PH-responsive drug release system based on the conjugates of PAMAM dendrimers–doxorubicin (PAMAM–DOX) and superparamagnetic iron oxide (Fe3O4) nanoparticles (IONPs) has been constructed and characterized. The IONPs were stabilized by mPEG-G2.5 PAMAM dendrimers. The anticancer drug DOX was conjugated to the dendrimer segments of amino-stabilized IONPs using hydrazine as the linker via hydrazone bonds, which is acid cleavable and can be used as an ideal pH-responsive drug release system. The drug release profiles of DOX–PAMAM dendrimer conjugates were studied at pH 5.0 and 7.4. The results showed that the hydrolytic release profile can be obtained only at the condition of lysosomal pH (pH = 5.0), and IONPs participated in carrying DOX to the tumor by the Enhanced Permeability and Retention (EPR) effect. These novel DOX-conjugated IONPs have the potential to enhance the effect of MRI contrast and cancer therapy in the course of delivering anticancer drugs to their target sites. Although the dendrimer–DOX-coated IONPs do not have any targeting ligands attached on their surface, they are potentially useful for cancer diagnosis in vivo.

Schematic diagram showing direct exchange reactions between the monovalent capping ligand ODA and the mPEG-G2.5-DOX ligand and the conjugates injected to the tumor-bearing mice..Figure optionsDownload high-quality image (34 K)Download as PowerPoint slideHighlights
► The novel strategies to prepare PAMAM-Dox-conjugated Iron oxide NPs.
► Conjugates were dual functional nanoparticles for tumor imaging and tumor therapy via the EPR effect.
► It was a pH-controlled release system, which can only release at low pH environment.
► Conjugates contained IONPs which could be used as magnetic resonance imaging contrast agent.