Blood‐Brain Barrier Permeable Gold Nanoparticles: An Efficient Delivery Platform for Enhanced Malignant Glioma Therapy and Imaging

Abstract

The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, we demonstrate that a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd3+ contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, we demonstrate that TAT-Au NPs are capable of delivering Gd3+ chelates for enhanced brain tumor imaging with a prolonged retention time of Gd3+ when compared to the free Gd3+ chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.

Coadministration of Vascular Disrupting Agents and Nanomedicines to Eradicate Tumors from Peripheral and Central Regions

“…H&E Staining : Balb/C nude mice bearing an MDA-MB-435 tumor (300-400 mm 3 ) were injected with CDDP-NPs (4 mg CDDP equivalent kg ). The mice were sacrifi ced at 72 h. After the mice were sacrifi ced, tumors were collected, embedded with paraffi n, and stained with H&E. The histological alterations were observed by microscopy (Nikon TI-S/L100).…”

Hair follicles as a target structure for nanoparticles

“…[1][2][3][4] These research activities were stimulated by experiments which showed that nanoparticles penetrated e±ciently through the blood-brain barrier. 5 However, a commercial product for nanoparticle-assisted delivery of drugs through the cutaneous barrier is still lacking. The¯rst investigations showing that nanoparticles can penetrate into the hair follicles were performed using sunscreens that contained not only chemical UV¯lters but also physical¯lters in the form of TiO 2 nanoparticles.…”

Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

“…Cell mediated strategy that can effectively circumvent the biological barriers has aroused extensive attention in the treatment of many kinds of tumors [25,26]. Among them, macrophages are attractive due to their innate phagocytotic capability.…”