Magnetic nanoparticles as heat-generating nanosources in hyperthermia treatment are still faced with many drawbacks for achieving sufficient clinical potential. In this context, increase in heating ...ability of magnetic nanoparticles in a biologically safe alternating magnetic field and also approach to a precise control on temperature rise are two challenging subjects so that a significant part of researchers’ efforts has been devoted to them. Since a deep understanding of Physics concepts of heat generation by magnetic nanoparticles is essential to develop hyperthermia as a cancer treatment with non-adverse side effects, this review focuses on different mechanisms responsible for heat dissipation in a radio frequency magnetic field. Moreover, particular attention is given to ferrite-based nanoparticles because of their suitability in radio frequency magnetic fields. Also, the key role of Curie temperature in suppressing undesired temperature rise is highlighted.
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•In MHT, the heat generated by MNPs is produced by independent mechanisms.•MHT demands MNPs with high heating efficiency in a safe alternating magnetic field.•Undesired temperature rise can be inhibited through Curie temperature of MNPs.•This review discusses about the Physics concepts involved in the above subjects.
We present a study on the magnetic behavior of dextran-coated magnetite nanoparticles (DM NPs) with sizes between 3 and 19 nm, synthesized by hydrothermal-assisted co-precipitation method. The ...decrease of saturation magnetization (
M
s
) with decreasing particle size has been modeled by assuming the existence of a spin-disordered layer at the particle surface, which is magnetically dead. Based on this core–shell model and taking into account the weight contribution of non-magnetic coating layer (dextran) to the whole magnetization, the dead layer thickness (
t
) and saturation magnetization
M
s
of the magnetic cores in our samples were estimated to be
t
=
6.8 Å and
M
s
=
98.8
emu
/
g
, respectively. The data of
M
s
were analyzed using a law of approach to saturation, indicating an increase in effective magnetic anisotropy (
K
eff
) with decreasing the particle size as expected from the increased surface/volume ratio in small MNPs. The obtained
K
eff
values were successfully modeled by including an extra contribution of dipolar interactions due to the formation of chain-like clusters of MNPs. The surface magnetic anisotropy (
K
s
) was estimated to be about
K
s
=
1.04
×
10
5
J
/
m
3
. Our method provides a simple and accurate way to obtain the
M
s
core values in surface-disordered MNPs, a relevant parameter required for magnetic modeling in many applications.
Graphical abstract
Folate-targeted iron oxide nanoparticles (FA@Fe
O
NPs) were prepared by a one-pot hydrothermal method and then used as cancer theranostic agents by combining magnetic resonance imaging (MRI) and ...magnetic hyperthermia therapy (MHT). Crystal structure, morphology, magnetic properties, surface functional group, and heating efficacy of the synthesized nanoparticles were characterized by XRD, TEM, VSM, FTIR, and hyperthermia analyses. The results indicated that the crystal structure, magnetic properties, and heating efficacy of the magnetite nanoparticles were improved by hydrothermal treatment. Toxicity of the prepared NPs was assessed in vitro and in vivo on the mammary cells and BALB/c mice, respectively. The results of the in vitro toxicity analysis showed that the FA@Fe
O
NPs are relatively safe even at high concentrations of the NPs up to 1000 µg mL
. Also, the targetability of the FA@Fe
O
NPs for the detection of folate over-expressed cancer cells was evaluated in an animal model of breast tumor using MRI analysis. It was observed that T
-weighted magnetic resonance signal intensity was decreased with the three-time injection of the FA@Fe
O
NPs with 24 h interval at a safe dose (50 mg kg
), indicating the accumulation and retention of the NPs within the tumor tissues. Moreover, the therapeutic efficacy of the MHT using the FA@Fe
O
NPs was evaluated in vivo in breast tumor-bearing mice. Hyperthermia treatment was carried out under a safe alternating magnetic field permissible for magnetic hyperthermia treatment (f = 150 kHz, H = 12.5 mT). The therapeutic effects of the MHT were evaluated by monitoring the tumor volume during the treatment period. The results showed that the mice in the control group experienced an almost 3.5-fold increase in the tumor volume during 15 days, while, the mice in the MHT group had a mild increase in the tumor volume (1.8-fold) within the same period (P < 0.05). These outcomes give promise that FA@Fe
O
NPs can be used as theranostic agents for the MRI and MHT applications.
Abstract
Successful cancer treatment using magnetic hyperthermia therapy (MHT) strongly depends on biocompatible magnetic nanoparticles (NPs). They can effectively accumulate in tumor tissues after ...systemic injection and generate heat in the therapeutic temperature range (42–48 °C) by exposure to an AC magnetic field (AMF). For this purpose, folic acid-conjugated dextran-coated Zn
0.6
Mn
0.4
Fe
2
O
4
(FA-Dex-ZMF) NPs were synthesized as smart nano heaters with self-regulating temperatures for MHT of liver tumors. Animal studies on BALB/c mice showed that the prepared NPs did not cause acute toxicity upon administration up to 100 mg kg
−1
. Likewise, no significant changes in hematological and biochemical factors were observed. FA-Dex-ZMF NPs were studied by exposing them to different safe AC magnetic fields (f = 150 kHz, H = 6, 8, and 10 kA m
−1
). Calorimetric experiments revealed that the NPs reached the desired temperature range (42–48 °C), which was suitable for MHT. Moreover, the efficacy of FA-Dex-ZMF NPs in MHT of liver tumors was investigated in vivo in liver-tumor-bearing mice. The obtained results revealed that the average volume of tumors in the control group increased 2.2 times during the study period. In contrast, the tumor volume remained almost constant during treatment in the MHT group. The results indicated that folic acid-conjugated dextran-coated Zn
0.6
Mn
0.4
Fe
2
O
4
NPs with self-regulating temperature could be a promising tool for systemically delivered MHT.
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•A facile one-pot hydrothermal method was presented for preparation of hyaluronic acid-coated Fe3O4 nanoparticles.•Uptake of the Fe3O4@HA NPs by MDA-MB-231 cells was found to be ...4-fold higher than the normal cells.•The ILP value for Fe3O4@HA NPs was about 3.5 nHm2/kg, which is about 25-fold larger than that of obtained for Feridex.
In the present study, a facile one-pot hydrothermal method is introduced for preparation of hyaluronic acid-coated Fe3O4 nanoparticles (Fe3O4@HA NPs) for theranostic applications. In the proposed method, hyaluronic acid acts simultaneously as a biocompatible coating layer and as a targeting ligand for CD44 receptor overexpressed on the surface of breast cancer cells. The obtained product with narrow hydrodynamic size distribution exhibited a high colloidal stability at physiological pH for more than three months. Cytotoxicity measurements indicated a negligible toxicity of the prepared sample against L929 normal cells. Preferential targeting of Fe3O4@HA NPs to CD44-overexpressing cancer cells was studied by comparing the uptake of the prepared nanoparticles by MDA-MB-231 cancer cells (positive CD44 expression) and L929 normal cells (negative CD44 expression). Uptake of the Fe3O4@HA NPs by MDA-MB-231 cells was found to be 4-fold higher than the normal cells. Also, the in vitro analysis showed that, the uptake of Fe3O4@HA NPs by MDA-MB-231 breast cancer cells is significantly enhanced as compared to non-targeted dextran-coated Fe3O4 NPs. Moreover, the heat generation capability of the Fe3O4@HA NPs for magnetic hyperthermia application was studied by exposing the prepared nanoparticles to different safe alternating magnetic fields (f = 120 kHz, H = 8, 10, and 12 kA/m). The intrinsic loss power obtained for Fe3O4@HA NPs was about 3.5 nHm2/kg, which is about 25-fold larger than that of obtained for commercial available Fe3O4 nanoparticles for biomedical applications. Good colloidal stability, biocompatibility, high heating efficacy, and targeting specificity to CD44 receptor‐overexpressing cancer cells could make the Fe3O4@HA NPs as a promising multifunctional platform for diagnosis and therapeutic applications.
Stimuli-responsive polymers have been of great interest in the fabrication of advanced drug delivery systems. In this study, a facile approach was developed to synthesize a dually ...temperature/pH-responsive drug delivery system with a core-shell structure to control the release of doxorubicin (DOX) at the target site. For this purpose, poly(acrylic acid) (PAA) nanospheres were first synthesized using the precipitation polymerization technique and were used as pH-responsive polymeric cores. Then, poly(N-isopropylacrylamide) (PNIPAM) with thermo-responsivity properties was coated on the outer surface of PAA cores via seed emulsion polymerization technique to render monodisperse PNIPAM-coated PAA (PNIPAM@PAA) nanospheres. The optimized PNIPAM@PAA nanospheres with an average particle size of 116.8 nm (PDI= 0.243), had a high negative surface charge (zeta potential= -47.6 mV). Then, DOX was loaded on PNIPAM@PAA nanospheres and the entrapment efficiency (EE) and drug loading (DL) capacity were measured to be 92.7% and 18.5%, respectively. The drug-loaded nanospheres exhibited a low leakage at neutral pH and physiological temperature, but drug release significantly enhanced at acidic pH (pH= 5.5), indicating the tumor-environment responsive drug release behavior of the prepared nanospheres. Also, kinetics studies showed that, the sustained release of DOX from PNIPAM@PAA nanospheres was consistent with the Fickian diffusion mechanism. Moreover, the anticancer efficacy of DOX-loaded nanospheres was evaluated in vitro against MCF-7 breast cancer cells. The obtained results revealed that, the incorporation of DOX into PNIPAM@PAA nanospheres increases its cytotoxicity against cancer cells compared to the free DOX. Our results suggest that, PNIPAM@PAA nanospheres can be considered as a promising vector to release anticancer drugs with dual-stimuli responsivity to pH and temperature.
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Most of the employed methods for preparation of targeted nanoparticles containing hydrophobic herbal drugs have multiple surface modifications with time-consuming steps. The present ...research was aimed to develop a facile method for preparation of hyaluronic acid (HA)-decorated mixed nanomicelles loaded with curcumin (as a hydrophobic drug model) to provide an efficient drug delivery system for targeted therapy of breast cancer cells with high expression of CD44 receptor. To this end, curcumin was first encapsulated in the hydrophobic core of Pluronic F127/didecyldimethylammonium bromide (PD) mixed nanomicelles using thin-film hydration method. Then, negatively charged HA was coated on the positively charged surface of PD mixed nanomicelles via electrostatic interactions. The drug loading and entrapment efficiency of the targeted nanomicelles were 2.8% and 95.1%, respectively. The average hydrodynamic size of the prepared nanomicelles before and after coating with HA were 19.8 and 35.8 nm, respectively. Moreover, in vitro cytotoxicity analyses showed that, HA-coated PD (HA-PD) mixed nanomicelles can enhance the cytotoxicity of curcumin against MDA-MB-231 cancer cells compared to non-targeted ones (PD mixed nanomicelles), and free curcumin. The IC50 concentrations of free curcumin, curcumin-loaded PD mixed nanomicelles, and curcumin-loaded HA-PD mixed nanomicelles were 4.11, 3.20, and 2.83 μg/mL, respectively, after 48 h incubation with MDA-MB-231 cancer cells. Our results suggest that, curcumin-loaded HA-PD mixed nanomicelles may be considered as a promising targeted anticancer drug delivery system for breast cancer therapy and/or delivering other hydrophobic drugs to different kinds of cancer cells with CD44-receptor overexpression.
In the current study, a combination of precipitation polymerization and modified sol-gel methods were developed to prepare the novel hyaluronic acid-decorated pH and redox dual-stimuli responsive ...poly(methacrylic acid)/mesoporous organosilica nanoparticles with a core-shell structure for controlled drug release. The nanocarriers have a proper particle size of <200 nm, high negative zeta potential greater than −30 mV, controllable diameter, and tunable shell thickness. The prepared nanoparticles were able to entrap over 70 % of quercetin with a drug loading of >10 %, due to the mesoporous shell. In vitro drug release profiles indicated that the systems had good stability under normal physiological media, while the cumulative release was significantly accelerated at the simulated tumor tissue condition, which shows pH and redox-dependent drug release. In vitro cell viability and apoptosis assay proved that the obtained nanomaterials possess relatively good biocompatibility, and drug-loaded targeted nanoparticles exhibited greater cytotoxicity on MCF-7 human breast cancer cells than free drug and non-targeted nanocarriers due to the enhanced cellular uptake of nanoparticles via CD44 receptors overexpressed. All these findings demonstrated that proposed nanocarriers might be promising as a smart drug delivery system to improve the antitumor efficacy of chemotherapeutic drugs.
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•HA-MON/PMAA as a pH/redox responsive drug delivery system was developed.•HA-MON/PMAA has a high QUE loading efficiency and exhibited dual-sensitive release.•QUE-loaded HA-MON/PMAA presented high cytotoxicity to MCF-7 breast cancer cells.
The majority of herbal anticancer drugs are insoluble in water or become unstable during their transport to tumor tissues, hence they require a special drug delivery system. The main target of this ...study was to evaluate the therapeutic efficacy of silibinin (SLB)-loaded folic acid (FA)-conjugated Pluronic F127 (SLB-F127-FA) nanomicelles as an active-targeted drug delivery platform for liver cancer treatment. To prepare SLB-F127-FA nanomicelles, folic acid was first conjugated to hydrophilic chains of Pluronic F127 copolymer by the Steglich esterification technique. Then, silibinin was encapsulated in the self-assembled hydrophobic core of FA-conjugated F127 to render SLB-F127-FA nanomicelles. The prepared nano micelles had an almost spherical shape with an average particle size of 17.7 nm. The average hydrodynamic size of non-targeted (SLB-F127) and targeted (SLB-F127-FA) nanomicelles, measured by dynamic light scattering analysis (DLS), was 19.6 and 29.2 nm, respectively. Also, the drug loading content as well as entrapment efficiency of SLB-F127-FA nanomicelles were obtained to be 2.36% and 79.43%, respectively. The in vitro release patterns of SLB from nanomicelles showed a slow and sustained release behavior in comparison to free SLB. Moreover, it was observed that the kinetic release of silibinin from the SLB-F127-FA nanomicelles at 37 °C conforms well to Korsmeyer-Peppas kinetic model (R2 = 0.99, n = 0.22), suggesting a dominate release mechanism of the Fickian diffusion type. Moreover, in vitro cytotoxic study indicated that the viability of human liver cancer cells (HepG2) exposed to SLB-PF127-FA nanomicelles was significantly lower than that of treated with non-targeted nanomicelles (SLB-F127) or free SLB. Our results suggest that SLB-F127-FA nanomicelles can be considered as a promising targeted drug delivery platform for liver cancer therapy and/or delivering other hydrophobic drugs to different types of cancers with folate-receptor overexpression.
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Magnetic nanoparticles with improved heating efficiency are required for an efficient magnetic hyperthermia therapy. In this study, monodisperse CuFe2O4 nanoparticles (NPs) with higher heat ...generation capability compared to Fe3O4 NPs were synthesized by a solvothermal method using triethylene glycol as solvent, reductant, and stabilizer. X-ray diffraction (XRD) analysis confirmed the single phase formation of CuFe2O4 and Fe3O4 NPs under experimental conditions. Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of TREG molecules on the surface of both samples. Nanoparticles with spherical shape were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with an average particle size of 19.9 and 18.5 nm for CuFe2O4 and Fe3O4 NPs, respectively. The room temperature magnetic measurements indicated that both samples are in the vicinity of transition point from superparamagnetic to single-domain ferromagnetic state with a saturation magnetization of 53.1 and 58.8 emu/g for CuFe2O4 and Fe3O4 NPs, respectively. Moreover, CuFe2O4 NPs showed the lower anisotropy energy compared to Fe3O4 NPs, leading to the faster approach to saturation and slightly more rectangular hysteresis loop. The heating efficacy of the CuFe2O4 and Fe3O4 NPs were investigated under different safe alternating magnetic fields permissible for magnetic hyperthermia therapy (f = 120 kHz, H = 13, 16, and 19 kA/m). The maximum specific absorption rate (SAR) obtained for CuFe2O4 and Fe3O4 NPs were 44.9 and 18.5 W/g, respectively, at magnetic field intensity of 19 kA/m and frequency of 120 kHz. The two-fold increase in the SAR value of the CuFe2O4 NPs compared to the Fe3O4 NPs might be attributed to the tuning and better matching of their anisotropy energy with frequency and magnetic field intensity used in magnetic hyperthermia experiments.
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•Monodispersed CuFe2O4 and Fe3O4 nanoparticles were obtained via solvothermal method.•Induction heating studies under safe alternating magnetic fields revealed high SAR value for CuFe2O4 nanoparticles.•The intrinsic loss power (ILP) of CuFe2O4 nanoparticles was about 1.23 nHm2 kg−1 which is proper for hyperthermia therapy.
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