Title : Theranostic anti-glioma intelligent nanoplatform, CA and radiation sensitizer

Glioblastoma multiforme (GBM) treatment poses significant challenges due to factors such as the blood-brain barrier (BBB), poor diagnostic capabilities at the cellular level, resistance to conventional therapies, and the invasive nature of the tumors. In this study, we present an anti-glioblastoma theranostic nanoplatform decorated with PEG-RVG15 to enhance BBB penetration and target GBM selectively. This nanoplatform is loaded with Apoptin within an acid-sensitive ZIF-8, allowing for selective apoptosis of GBM cells while preserving normal cells in the tumor’s acidic microenvironment.

Additionally, the core of the platform contains iron oxide nanoparticles (IONPs) coated with citrate, which serve as an imaging contrast agent and produce reactive oxygen species (ROS) under 1 Gy X-ray radiation. We also employed a 350 kHz radio frequency (RF) to incorporate hyperthermic therapy and diagnosis, heating the IONPs inside GBM cells to 43°C for further treatment and infrared imaging.

According to the MTT test results, this smart anti-GBM theranostic method, utilizing the intravascularly administered synthesized nanoplatform (IONP-Citrate-Apoptin@ZIF-8-PEG-RVG15) along with X-ray (1 Gy) and RF (350 kHz), effectively killed 100% of GBM cells while damaging only 6% of normal brain cells. Overall, we report an effective method for GBM theranostics.

Zeta potential test confirmed the positive charge of the nanoplatform, which is essential in crossing the BBB and targeting GBM cells. DLS and TEM results confirm the nanoplatform's mean size to be 150 nm, which is the optimum size for natural and positively charged nanoparticles for tumor treatment in the brain. FTIR confirmed each agent attachment on the surface of the nanoplatform.

Briefly, IONPs were synthesized with the co-participation method and coated with citric acid at 65 °C for 25 min. Apoptin was loaded inside ZIF-8 by mixing Apoptin and 2-methylimidazole (2-Mim), followed by the addition of Zn²⁺ ions. RVG15-PEG₂₀₀₀-COOH was synthesized by conjugating the cysteine residue of RVG15-Cys to COOH-PEG₂₀₀₀-Mal; and was attached to the ZIF-8 surface via electrostatic interactions.

Mohammad-Nabil Savari holds a BS in Biology from Shahid Beheshti University, as well as an MS and a Ph.D. in Medical Nanotechnology (Nano Medicine) from the Tehran Medical Branch of Islamic Azad University in Tehran, Iran. He is the author of the book titled “Theranostic Iron-Oxide Based Nanoplatforms in Oncology: Synthesis, Metabolism, and Toxicity for Simultaneous Imaging and Therapy,” published by Springer Nature. Additionally, he served as a peer reviewer for "Cancer Reports" (Wiley) and "ACS Applied Nano Materials." His research papers and interests focus on the development of anti-glioma smart theranostic nanoplatforms and their integration with medical physics devices such as MRI, radiotherapy, radio frequency hyperthermia, and phototherapy.