GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells

• Published in: Colloids and surfaces. A, Physicochemical and engineering aspects Vol. 622; p. 126648
• Main Authors: Senturk, Fatih, Cakmak, Soner, Kocum, Ismail Cengiz, Gumusderelioglu, Menemse, Ozturk, Goknur Guler
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-08-2021
• Subjects: Curcumin; Glioblastoma; GRGDS; Magnetic nanoparticles; RF hyperthermia; Curcumin; RF hyperthermia; GRGDS; Glioblastoma; Magnetic nanoparticles
• ISSN: 0927-7757; 1873-4359
• DOI: 10.1016/j.colsurfa.2021.126648

Thermally responsive and ligand-mediated drug delivery systems have the potential to improve the treatment of brain tumors, especially, most lethal one, glioblastoma multiform (GBM). Magnetic nanoparticle-mediated hyperthermia becomes one of the most promising alternative therapy for GBM treatment in cases where localized heating and targeted delivery of a therapeutic drug can be achieved on the tumor site. In this study, it is aimed to increase the therapeutic efficiency of multi-functionalized nanoparticles (NPs) in combination with radiofrequency hyperthermia (RF-HT) on GBM cells. For this purpose, firstly, a low-cost and portable home-built RF-HT system suitable for in vitro/in vivo studies was successfully implemented and tested at 13.56 MHz frequency with power up to approximately 400 W. Subsequently, the highly monodispersed superparamagnetic iron oxide nanoparticles (SPIONs), which could interact with the RF magnetic field, were synthesized with the mean particle size of 5.6 ± 0.9 nm. The obtained SPIONs were coated with poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG). Most of the SPIONs were uniformly distributed in such a well-defined spherical-shaped polymeric NP. Moreover, curcumin (Cur), a potential agent for GBM treatment, was loaded into the magnetic polymeric nanoparticles (m-PNPs) with a loading capacity of 8% (w/w, Cur/NPs) and a mean diameter of Cur-loaded m-PNPs (Cur-m-PNPs) was 142 ± 70 nm. To increase cellular uptake and targeting ability of NPs, glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide was immobilized on the Cur-m-PNPs and the amount of GRGDS was detected as 37 µg/mg NPs. In vitro cytotoxicity studies revealed that the presence of GRGDS on Cur-m-PNPs (GRGDS-Cur-m-PNPs) improved the cytotoxic efficiency of Cur-m-PNPs by 6-fold in GBM cells for all incubation times (24, 48 and 72 h). Furthermore, NPs with RF treatment exhibited higher antitumor activity than that of NPs without RF on GBM cells. This result may be attributed to the thermal (SPIONs) or non-thermal (cellular membrane) effects or both of them on cells. Overall, this study showed that RF-HT in combination with GRGDS-Cur-m-PNPs could provide a feasible approach to improve GBM treatment.
GRGDS-conjugated magnetic polymeric nanoparticles were synthesized as a carrier of curcumin and SPIONs for improving targeting therapeutic efficiency on the glioblastoma cell lines. Also, a novel home-built RF-HT system was implemented and combined with nanoparticles to increase therapeutic efficiency on GBM cells (created by biorender.com except for fluorescence images) (300 dpi) [Display omitted]
•Dual encapsulation of SPIONs and curcumin in polymeric nanoparticles (Cur-m-PNPs).•GRGDS conjugation to Cur-m-PNPs reduced cytotoxic dose of free curcumin by 2.5-fold.•Multifunctional m-PNPs showed effective heating performance under AC magnetic field.•High therapeutic efficacy in T98G cells was achieved via multifunctional m-PNP induced hyperthermia.