Construction of multifunctional targeted nano-prodrugs based on PAMAM dendrimers for tumor therapy

Abstract

Nanomaterial-based drug delivery systems have demonstrated powerful applications in tumor therapy. PAMAM dendrimers by virtue of multivalent modification and biocompatible components were widely used to construction multifunctional targeted chemotherapeutics. In this report, we present a PAMAM dendrimer-based nano-prodrug delivery system for targeted tumor therapy. The RGDyC-PEG-PAMAM-PBA-Res (RPPPR) nano-prodrug was characterized by 1H NMR, zetasizer, and TEM, the drug loading and pH-sensitive drug release behaviors were investigated. In vitro cell viability assay revealed that the group treated with the nano-prodrug exhibited lower cell viability compared to the control group as concentration increased, confirming the nano-prodrug’s effectiveness in treating tumors. In vitro studies on cellular uptake of the nano-prodrug demonstrated that RPPPR had a high targeting ability, primarily attributed to the RGD-mediated target effect. Relevant data from our hemolysis assay indicated that the nano-prodrug maintained good blood compatibility within the concentration range of 0.1 to 0.3 mg/mL. In vivo experiments focusing on tumor therapy showed that RPPPR suppressed tumor growth and promoted tumor apoptosis. H&E staining, TUNEL assay, and immunohistochemistry results further validated the enhanced therapeutic effect. Importantly, no toxicity was observed in the vital organs such as the heart, liver, lung, kidneys, or spleen. These results suggest the superior antitumor efficacy of RPPPR compared to Resveratrol alone, and thus may be useful for tumor therapy. It is expected to explore new directions to establish a general strategy with dendritic prodrugs for synergistic tumor targeting therapy.