Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia and dual stimuli-responsive drug delivery

Abstract

The synthesis of hydrophilic graphene-based yolk-shell magnetic nanoparticles functionalized with copolymer pluronic F-127 (GYSMNP@PF127) is herein reported to achieve an efficient multifunctional biomedical system for mild hyperthermia and stimuli-responsive drug delivery. In vitro tests revealed the extraordinary ability of GYSMNP@PF127 to act as smart stimuli-responsive multifunctional nanomedicine platform for cancer therapy, exhibiting (i) an outstanding loading capacity of 91% (w/w, representing 910 μg mg −1) of the chemotherapeutic drug doxorubicin, (ii) a high heating efficiency under an alternating (AC) magnetic field (intrinsic power loss ranging from 2.1-2.7 nHm 2 kg −1), and (iii) a dual pH and thermal stimuli-responsive drug controlled release (46% at acidic tumour pH vs 7% at physiological pH) under AC magnetic field, in just 30 min. Additionally, GYSMNP@PF127 presents optimal hydrodynamic diameter (D H = 180 nm) with negative surface charge, high haemocompatibility for blood stream applications and tumour cellular uptake of drug nanocarriers. Due to its physicochemical, magnetic and biocompatibility properties, the developed graphene-based magnetic nanocarrier shows high promise as dual exogenous (AC field)/endogenous (pH) stimuli-responsive actuators for targeted thermo-chemotherapy, combining magnetic hyperthermia and controlled drug release triggered by the abnormal tumour environment. The presented strategy and findings can represent a new way to design and develop highly stable added-value graphene-based nanostructures for the combined treatment of cancer.

Graphenic Materials for Biomedical Applications

“…In addition, HeLa cells were 13% more sensitive to DOX in this system than normal cells, confirming the selective role of concanavalin A [167]. The in vitro screening of multifunctional hydrophilic magnetic NPs based on egg yolk-functionalized Pluronic™ F-127 (GYSMNP@PF127), with a particle size of 180 nm, a negative surface charge, and high hemocompatibility, showed a high capacity of 91% w/w for DOX, with a high heating effect with an alternating (AC) magnetic field (internal energy loss in the range of 2.1 to 2.7 nHm 2 /kg), a controlled release of the pH responsive drug, and thermal stimulus (46% at the acidic pH of the tumor and 7% at the physiological pH) when in an alternating magnetic field (MF) [168]. The multifunctional NPs, with a diameter of 71.8 nm and zeta potential of −333.07 ± 0.07 mV, prepared from GO coated with superparamagnetic iron oxide nanoparticles (SPIONs) and poly(lactic-co-glycolic acid) (PLGA), was able to load 3.04 ± 0.46% radiosensitizing 5-iodine-2-deoxyuridine (IUdR) and provided targeted delivery to gliomas.…”

Carbon-Based Magnetic Nanocarrier for Controlled Drug Release: A Green Synthesis Approach

“…The result of the Zeta potential measurement showed the magnitude −22.1 ± 4.1 mV for CMNPs-plur sample (Figure 8b). The negative charge observed in the material can be explained by two main factors: the incorporation of carboxylic acid groups (via acid treatment) and the previously reported associated negative charge of materials functionalized with Pluronic [28,34,35], resulting in a consequent increase of the colloidal stability. In addition, the negative surface charge is attributed to the increased circulation of nanoparticles.…”

“…Finally, having done the last washing with ethanol absolute, the MNPs were dried at 60 • C in the drying oven. The resultant NPs were denoted Fe 3 O 4 @polymer [19,28].…”

“…The carbonization occurred up to 600 • C at a heating rate of 1 • C·min −1 and the temperature was maintained at 600 • C for 3 h. The resultant NPs were etched under stirring with sodium hydroxide solution (10 mol·L −1 for 24 h at room temperature) and the product was washed by centrifugation with distilled water several times, until reaching pH 7. In the last step, the sample was washed with ethanol and dried at 60 • C in a drying oven [19,28] (CMNPs).…”

“…In addition, the negative surface charge is attributed to the increased circulation of nanoparticles. This fact would be positive in future in vitro cellular applications, since it may avoid the phenomenon of opsonization (a process by which the plasma immunoproteins bind to the surface of the particle leading to elimination of nanoparticles by macrophages) [28,36]. Moreover, the negative charge of the studied nanoparticles, which is advantage for the combination of this material with the cationic drug Doxorubicin (which has NH3 + group).…”