Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

Abstract

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

Nanoparticles for Brain-Specific Drug and Genetic Material delivery, Imaging and Diagnosis

“…Several strategies have been used to improve the CNS crossing abilities of AuNPs, such as an MRI-guided focused ultrasound technique that enhances the BBB permeability and brain delivery of AuNPs [99]. However, most of them explore a strategy based on incorporating several targeting peptides into the AuNPs, including: the peptide THRPPM-WSPVWP, which binds to the transferrin receptor and increases the permeability of AuNPs in brain [100]; the incorporation of the transactivator of transcription (TAT) peptide to AUNPs to increase BBB crossing and deliver doxorubicin and gadolinium to brain tumor tissues [101]; the combination of the OX26 antibody with pegylated cationic solid lipid AuNPs, leading to the increased delivery of AUNPs to the brain [102] and by Angiopep-2 functionalization of pegylated AuNPs loaded with doxorubicin, which allowed in vivo distribution of nanoparticles into glioma brain xenografts and prolonged mice survival rate [103].…”

Tumor-targeted and pH-controlled delivery of doxorubicin using gold nanorods for lung cancer therapy

“…11,12 TfR-targeted drug delivery to tumor cells can be achieved by conjugation of its natural ligand, transferrin (Tf), or monoclonal antibodies against TfR to nanoparticles (NPs) of various formulations. 13,14 Gold-based NPs are promising candidates as drug carriers because they are inert, biocompatible, their surface can easily be modified, and they exhibit adequate cell penetration. 15 Among the gold-based NPs, gold nanorods (GNR) have been extensively studied, due to their prolonged stability, ability to function as contrast agents, and capability of delivering drugs, DNA, small interfering ribonucleic acid, and proteins.…”

Imaging Fast Cellular Uptake of Polymer Dots via Receptor-Mediated Endocytosis

“…To our best knowledge, the common nanoparticle systems, including liposomes [19,20], metallic nanoparticles [21,22], magnetic nanoparticles [23,24] and quantum dots [25][26][27][28][29], have been employed for the investigations. Among the family of fluorescent probes, organic semiconductor polymer dots (Pdots) have been receiving considerable attention in the past decades because of many fascinating physical properties.…”