Polyamidoamine dendrimers enable dual delivery of doxorubicin and zidovudine for enhanced breast cancer therapy

Poly(amidoamine) (PAMAM) dendrimers have gained significant attention as nanocarriers due to their highly branched architecture, monodispersity, and ease of functional modification. In this study, a dual-drug delivery system based on Generation 4 PAMAM dendrimers was developed to co-deliver doxorubicin (DOX) and zidovudine (AZT) for enhanced breast cancer therapy. Both drugs were physically encapsulated within the dendrimer matrix, and their interaction with PAMAM was confirmed through Fourier-transform infrared spectroscopy (FTIR) and high-resolution transmission electron microscopy (HRTEM). Drug loading produced a measurable increase in particle size and characteristic spectral shifts, confirming successful encapsulation. In vitro cytotoxicity studies using MCF-7 breast cancer cells demonstrated dose-dependent antiproliferative activity, with an IC₅₀ value of 211.6 µg/mL for the PAMAM–DOX–AZT formulation. The nanocarrier exhibited sustained drug release and reduced cell viability by ~ 58% at the highest tested concentration. The ability of PAMAM dendrimers to simultaneously deliver a conventional chemotherapeutic (DOX) and a telomerase-inhibiting nucleoside analog (AZT) highlights their potential to overcome drug-resistance mechanisms and improve therapeutic outcomes. Overall, the findings support PAMAM dendrimers as a versatile and efficient platform for combination chemotherapy in cancer treatment.