Cell-Penetrating Peptidic GRP78 Ligand-Conjugated Iron Oxide Magnetic Nanoparticles for Tumor-Targeted Doxorubicin Delivery and Imaging

Although chemotherapy is regarded as an essential option in cancer treatment, it is still far from being perfect. Inadequate tumor drug concentration and systemic toxicity along with broad biodistribution have diminished the utility of chemotherapy. Tumor-targeting peptide-conjugated multifunctional nanoplatforms have emerged as an effective strategy for site-directed tumor tissues in cancer treatment and imaging. Herein, Pep42-targeted iron oxide magnetic nanoparticles (IONPs) functionalized with β-cyclodextrin (ßCD) containing doxorubicin (DOX) (Fe 3 O 4 -ßCD-Pep42-DOX) were successfully developed. The physical effects of the prepared NPs were characterized by employing various techniques. Transmission electron microscopy (TEM) images disclosed that the developed Fe 3 O 4 -ßCD-Pep42-DOX nanoplatforms had a spherical morphology and a core–shell structure with a size of nearly 17 nm. Fourier transform infrared (FT-IR) spectroscopy showed that β-cyclodextrin, DOX, and Pep42 molecules were successfully loaded on the IONPs. In vitro cytotoxicity analysis revealed that the fabricated multifunctional Fe 3 O 4 -ßCD-Pep42 nanoplatforms possessed excellent biosafety toward BT-474, MDA-MB468 (cancerous cells), and MCF10A normal cells, while Fe 3 O 4 -ßCD-Pep42-DOX exhibited great cancer cell killing ability. The high cellular uptake along with intracellular trafficking of Fe 3 O 4 -ßCD-Pep42-DOX highlights the usefulness of the Pep42-targeting peptide. In vivo results strongly supported the in vitro results, i.e., significant tumor size reduction was observed by single-dose injection of Fe 3 O 4 -ßCD-Pep42-DOX into tumor-bearing mice. Interestingly, in vivo MR imaging (MRI) of Fe 3 O 4 -ßCD-Pep42-DOX revealed T 2 contrast improvement in the tumor cells and therapeutic ability in cancer theranostics. Taken together, these findings provided strong evidence for the potential capability of Fe 3 O 4 -ßCD-Pep42-DOX as a multifunctional nanoplatform in cancer therapy and imaging and opens up a new avenue of research in this area.