In Vitro Evaluation of Hyperthermia Magnetic Technique Indicating the Best Strategy for Internalization of Magnetic Nanoparticles Applied in Glioblastoma Tumor Cells

Javier B Mamani,Fernando A Oliveira,Luciana Marti,Taylla K F Souza,Mariana P Nucci,Arielly H Alves,Lionel F Gamarra,Leopoldo P Nucci,Gabriel N A Rego

doi:10.3390/pharmaceutics13081219

Abstract

This in vitro study aims to evaluate the magnetic hyperthermia (MHT) technique and the best strategy for internalization of magnetic nanoparticles coated with aminosilane (SPIONAmine) in glioblastoma tumor cells. SPIONAmine of 50 and 100 nm were used for specific absorption rate (SAR) analysis, performing the MHT with intensities of 50, 150, and 300 Gauss and frequencies varying between 305 and 557 kHz. The internalization strategy was performed using 100, 200, and 300 µgFe/mL of SPIONAmine, with or without Poly-L-Lysine (PLL) and filter, and with or without static or dynamic magnet field. The cell viability was evaluated after determination of MHT best condition of SPIONAmine internalization. The maximum SAR values of SPIONAmine (50 nm) and SPIONAmine (100 nm) identified were 184.41 W/g and 337.83 W/g, respectively, using a frequency of 557 kHz and intensity of 300 Gauss (≈23.93 kA/m). The best internalization strategy was 100 µgFe/mL of SPIONAmine (100 nm) using PLL with filter and dynamic magnet field, submitted to MHT for 40 min at 44 °C. This condition displayed 70.0% decreased in cell viability by flow cytometry and 68.1% by BLI. We can conclude that our study is promising as an antitumor treatment, based on intra- and extracellular MHT effects. The optimization of the nanoparticles internalization process associated with their magnetic characteristics potentiates the extracellular acute and late intracellular effect of MHT achieving greater efficiency in the therapeutic process.

Highlights

The treatment of cancer remains considered as one of the most challenging health issue
Process determination of the superparamagnetic iron were performed in a third phase, which consisted of magnetic hyperthermia (MHT) in vitro assays (Figure 1E), oxide nanoparticles coated with aminosilane (SPIONAmine —Figure 1A) using two superparamagnetic iron oxide nanoparticles (SPION)
The SPIONAmine (50 and 100 nm) displayed heating curves generated by MHT application combining the intensities and frequencies of magnetic fields parameters over time with fast increase of temperature at 150 and 300 Gauss compared to 50 Gauss, independently of the frequencies 305 and 557 kHz (Figure 2B,C)

Summary

Introduction

The treatment of cancer remains considered as one of the most challenging health issue. Intensive, and rapid advances in new technologies, drugs, and therapies against cancer during the last decades, the glioblastoma multiforme (GBM) is still the most prevalent (14.5% of all tumors and 48.6% of malignant tumors) and the most refractory of the gliomas in adults [1,2]. GMB represents 76% of all gliomas [3], with a high rate of patients deaths (15,000/year in the United States), and less than 10%. The main therapeutics approaches for GBM tumors include radiation therapy, chemotherapy, thermal therapy, and surgeries focusing on the best technique of tumor resection; these therapies can be used isolated or combined [6,7]. Pharmaceutics 2021, 13, 1219 further studies to improve and/or innovate the therapeutic approach for GBM are required. The treatments focusing on thermal heating are of great value, as tumor cells have lower tolerance to thermal variance effect compared to healthy cells [6]

Methods

Results

Conclusion