Mucin-1 conjugated polyamidoamine-based nanoparticles for image-guided delivery of gefitinib to breast cancer.

PAMAM dendrimers (PAMs) are a group of polymeric macromolecules with distinctive physicochemical features, which can make them multifunctional theranostic nanoparticles (NPs). This study was designed to examine the impact of mucin-1 aptamer-conjugated NPs which were engineered using PAM for image-guided delivery of gefitinib (GEF) in the breast cancer cells/tumor. For this, PAMAM was conjugated with diethylenetriaminepentaacetic acid (DTPA) and modified with PEG2000 to prepare a multi-functionalized NPs. Subsequently, GEF was loaded onto the DTPA-PAM-PEG NPs, which were then armed with MUC-1 aptamer to form the DTPA-PAM-PEG/GEF@MUC-1 nanosystem. Finally, aptamer-conjugated NPs were radiolabeled by gallium-67 as an imaging agent to construct image-guided nanoplatforms. The prepared NPs were characterized by different techniques. The kinetic release models of gefitinib from radiolabeled NPs offer the sustained-release mechanism of the encapsulated drug for over 7 days. In vitro evaluation showed higher cytotoxicity and enhanced uptake of the mucin-grafted NPs in MCF-7 cells. Nuclear medicine imaging and in vivo investigations revealed significant accumulation of Ga-DTPA-PAM-PEG/GEF@MUC-1 in the tumor site of the animal models. These data suggest that the engineered NPs are a promising image-guided nanosystem for mucin-expressing breast cells/tumors with the assistance of nuclear medicine.