Polyacrylic-conjugated polyamidoamine G4.0 dendrimer as a potential nanocarrier for effective delivery of cisplatin

Abstract

Platinum complexes have paid much attention to develop new drugs for cancer therapy due to its inhibitory activity against cancerous cell growth. In the study, the strategically programming cationic PAMAM G4.0 with carboxylate motifs was introduced as a delivery platform for cisplatin. Partial amino groups on the surface of PAMAM G4.0 had coupled with active carboxylate groups on polyacrylic acid (PAA) in order to reduce the remaining problem of cationic dendrimer and improve delivery effectiveness of aquated cisplatin. Our results show that the full cationic PAMAM G4.0 was toxic against both breast cancer (MCF7) and human dermal fibroblast (HuDF) cell lines at 100 ppm concentration. In the contract, the PAA-conjugated PAMAM G4.0 significantly improved their cytocompatibility of the cationic dendrimer. In addition, the modified PAMAM dendrimers G4.0 showed high affinity with the aquated cisplatin due to the presence of abundant carboxylic groups. Notably, the aquated cisplatin-complexed PAA-G4.0 showed 2.94-folded reduction in the toxicity against NCI H460 in comparison to free cisplatin drugs. Hence, the G4.0-PAA/aquated cisplatin nano-complex may become a promising versatile strategy for improving antitumour efficacy and reducing the side effects of platinum-based drugs.