In this work, we aim to synthesize water soluble and surface functionalized superparamagnetic iron oxide nanoparticles (SPIONs) using novel surfactants such as terephthalic acid (TA), 2-aminoterephthalic acid (ATA), trimesic acid (TMA) and pyromellitic acid (PMA) through one-step facile chemical co-precipitation and thermal decomposition methods. The as-synthesized SPIONs are characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS) measurements, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM). The as-synthesized SPIONs showed very good water solubility and a high magnetization value (Ms = 55-73 emu g-1). Furthermore, the as-synthesized ATA-coated SPIONs are conjugated with a fluorophore (Alexa Fluor 488) to demonstrate their ability for further chemical/biological conjugation without any additional surface modifications. Moreover, above 90\% cell viability in MCF-7 cancer cells has been observed, thus confirming good cytocompatibility of the SPIONs. Therefore, these hydrophilic and carboxyl-amine functionalized SPIONs are very promising candidates to be used for biomedical applications. © 2016 Royal Society of Chemistry.

Anindita Chakrabarty

Life Sciences

(SoNS) School of Natural Sciences

Kandasamy G.

Surendran S.

Kale S.N.

Maity D.

Fulltext

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Shiv Nadar University

RSC Advances

Background: Artesunate the most potent antimalarial is widely used for the treatment of multidrug-resistant malaria. The antimalarial cytotoxicity of artesunate has been mainly attributed to its selective, irreversible and iron- radical-mediated damage of parasite biomolecules. In the present research, iron oxide nanoparticle fortified artesunate was tested in P. falciparum and in an experimental malaria mouse model for enhancement in the selectivity and toxicity of artesunate towards parasite. Artesunate was fortified with nontoxic biocompatible surface modified iron oxide nanoparticle which is specially designed and synthesized for the sustained pH-dependent release of Fe2+ within the parasitic food vacuole for enhanced ROS spurt. Methods: Antimalarial efficacy of Iron oxide nanoparticle fortified artesunate was evaluated in wild type and artemisinin-resistant Plasmodium falciparum (R539T) grown in O + ve human blood and in Plasmodium berghei ANKA infected swiss albino mice. Internalization of nanoparticles, the pH-dependent release of Fe2+, production of reactive oxygen species and parasite biomolecule damage by iron oxide nanoparticle fortified artesunate was studied using various biochemical, biophysical, ultra-structural and fluorescence microscopy. For determining the efficacy of ATA-IONP+ART on resistant parasite ring survival assay was performed. Results: The nanoparticle fortified artesunate was highly efficient in the 1/8th concentration of artesunate IC50 and led to retarded growth of P. falciparum with significant damage to macromolecules mediated via enhanced ROS production. Similarly, preclinical In vivo studies also signified a radical reduction in parasitemia with ~8–10-fold reduced dosage of artesunate when fortified with iron oxide nanoparticles. Importantly, the ATA-IONP combination was efficacious against artemisinin-resistant parasites. Interpretation: Surface coated iron-oxide nanoparticle fortified artesunate can be developed into a potent therapeutic agent towards multidrug-resistant and artemisinin-resistant malaria in humans. Fund: This study is supported by the Centre for Study of Complex Malaria in India funded by the National Institute of Health, USA. © 2019

EBioMedicine

Pre-clinical study of iron oxide nanoparticles fortified artesunate for efficient targeting of malarial parasite

This work systematically describes one-step synthesis of hydrophilic functionalized superparamagnetic iron oxide nanoparticles (SPIONs) via thermolysis in presence of polyamines such as diethylene triamine (DETA), triethylene tetraamine (TETA), tetraethylene pentamine (TTEPA), or pentaethylene hexamine (PEHA) or mixture of a polyamine (TETA) and polyols such as diethylene glycol (DEG), triethylene glycol (TEG) or tetraethylene glycol (TTEG) while varying the polyamine: polyol (v/v) ratio, reaction temperature and reaction time. The saturation magnetization (Ms) values of the as-prepared polyamine (DETA/TETA/TTEPA/PEHA) coated SPIONs are determined in the range of 31.8–48.5 emu/g, which is altered in the range of 40.2–57.8 emu/g by the addition of a polyol (DEG/TEG/TTEG) to the polyamine (TETA) at different ratios. Moreover, the Ms. values are further improved to 64.6 and 66.8 emu/g at the optimized TETA:TEG (1:1) ratio by prolonging the reaction time up-to 2 h and the reaction temperature to 270 °C, respectively. In addition, the TETA-TEG coated SPIONs have displayed their average particle sizes, hydrodynamic sizes, and zeta potential (ζ) values in the range of 7–11 nm, 99–120 nm and +45 to +57 mV, respectively (indicating high water solubility). Finally, the TETA-TEG coated SPIONs with the highest Ms. and ζ values (i.e. 66.8 emu/g and +57 mV) are selected for the biological studies, where they have revealed excellent (i) cytocompatibility, and (ii) intracellular uptake in the cancer (HepG2 liver & MCF-7 breast) cells for the incubation periods of 24/48 h. Thus, the TETA-TEG coated SPIONs based aqueous ferrofluids have a great potential to be used in biomedical applications. © 2018 Elsevier B.V.

Journal of Molecular Liquids

One-step synthesis of hydrophilic functionalized and cytocompatible superparamagnetic iron oxide nanoparticles (SPIONs) based aqueous ferrofluids for biomedical applications

In this work, we have developed novel multifunctional magnetic-polymeric nanoparticles (MMPNs) based ferrofluids by encapsulating oleylamine (OM)-coated hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) inside the poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) individually, and along with two drugs such as curcumin (Cur, a chemotherapeutic drug (CHD)), and/or verapamil (Ver, a calcium channel blocker (CCB)). Herein, several parameters such as weighed amount (wt\%) of PLGA polymer (i.e., Resomer), stabilizer (i.e., polyvinyl alcohol (PVA)), organic solvents, amount of the SPIONs (in liquid suspension and powder forms), and amount of the drugs (i.e., Cur or/and Ver) are varied during the encapsulation process to optimize the formulation of PLGA NPs. The resulting polymeric NPs including empty PLGA NPs (i.e., without SPIONs/drugs), and MMPNs such as SPIONs-loaded PLGA NPs, Cur-SPIONs-loaded PLGA NPs, Ver-SPIONs-loaded PLGA NPs, and Cur-Ver-SPIONs-loaded PLGA NPs have displayed (i) hydrodynamic diameters and zeta potentials in the range of 280.8–287.3 nm, and −21 to – 26 mV, respectively, and (ii) better encapsulation efficiency for the SPIONs/Cur/Ver. In addition, the MMPNs have exhibited (i) magnetization values in the range of 7.6–9.5 emu/g with superparamagnetic behaviour, (ii) concentration based time-dependent temperature raise up-to 42 °C (minimum therapeutic temperature in magnetic fluid hyperthermia (MFH)/thermotherapy) with heating efficacies i.e., specific absorption rate (SAR) and intrinsic loss power (ILP) values ranging from 7 to 36 W/gFe and 0.1–0.4 nHm2/kg, respectively and (iii) better cytocompatibility. Finally, the SPIONs and dual-drugs (Cur &amp;Ver) co-loaded PLGA NPs have shown enhanced therapeutic efficacy in HepG2 cancer cells via combined therapies (i.e., thermotherapy and chemotherapy), as compared to the individual therapy (i.e., thermotherapy or chemotherapy) using the SPIONs/Cur/Ver loaded PLGA NPs. Thus, the as-prepared SPIONs/dual-drugs co-loaded PLGA NPs (i.e., MMPNs based ferrofluids) are potential therapeutic candidates for multi-modal treatment of cancer in vitro using thermotherapy and chemotherapy. © 2019 Elsevier B.V.

Multifunctional magnetic-polymeric nanoparticles based ferrofluids for multi-modal in vitro cancer treatment using thermotherapy and chemotherapy

We have systematically studied heating efficiencies (via specific absorption rate–SAR/intrinsic loss power-ILP) of carboxyl (terephthalic acid-TA) functionalized hydrophilic SPIONs based ferrofluids (with good biocompatibility/high magnetization) and influence of following key factors in magnetic fluid hyperthermia (MFH): (i) alternating magnetic fields (AMFs - H)/frequencies (f) - chosen below/above Hergt's biological safety limit, (ii) concentrations (0.5–8 mg/ml) and (iii) dispersion media (water, a cell-culture medium and triethylene glycol (TEG)) for in vitro cancer therapy. In calorimetric MFH, aqueous ferrofluids have displayed excellent time-dependent temperature rise for the applied AMFs, which resulted in high SAR ranging from 23.4 to 160.7 W/gFe, attributed to the enhanced magnetic responses via π-conjugations of short-chained TA molecules on the surface of SPIONs. Moreover, ILP values up-to 2.5 nHm2/kg (higher than the best commercial ferrofluids) are attained for the aqueous ferrofluids when excited below the recommended safety limit. Besides, the SPIONs dispersed in high viscous TEG have exhibited the highest SAR value (178.8 W/gFe) and reached therapeutic temperatures at faster rates for the lowest concentration due to prominent Neel relaxations. Moreover, these SPIONs have higher killing efficiency towards MCF-7 cancer cells in in vitro studies. Thus, the TA-based ferrofluids have great potential for in vivo/clinical MFH cancer therapies. © 2017 Elsevier Inc.

Journal of Colloid and Interface Science

Systematic magnetic fluid hyperthermia studies of carboxyl functionalized hydrophilic superparamagnetic iron oxide nanoparticles based ferrofluids

Here, we have studied the colloidal properties of carboxyl-amine functionalized superparamagnetic iron oxide nanoparticles (SPIONs with high saturation magnetization) based ferrofluids and their heating efficacies in magnetic fluid hyperthermia (MFH) via specific absorption rate (SAR)/intrinsic loss power (ILP). Moreover, we have systematically investigated the impact of the following heat influencing factors in MFH: (i) concentrations (0.5–8 mg/ml), (ii) surface coatings (trimesic acid (TMA), pyromellitic acid (PMA), terephthalic acid (TA) and aminoterephthalic acid (ATA)), (iii) applied alternating magnetic fields (AMFs - with amplitudes (H)/frequencies (f)) - chosen near to Hergt's biological safety limit, and (iv) dispersion media (biological/non-biological) for using SPIONs in in vitro cancer hyperthermia therapy. SPIONs (particularly decorated with dual-surfactants, i.e., TA-ATA) based aqueous ferrofluids have displayed excellent time-dependent temperature rise even at lower concentrations for the applied AMFs, which resulted in enhanced SAR values ranging from 12.5–200.1 W/gFe because of their high colloidal stability and enhanced π-π conjugations from the close structural orientations of TA/ATA molecules due to high electrostatic attractions of the respective functional groups (-COOH/NH2). Moreover, high ILP values of up-to 3.9 nHm2/kg (higher than the best commercial ferrofluids) are attained on exposure to magnetic fields below the safety limit. Besides, TA-ATA coated SPIONs dispersed in biological/non-biological media have exhibited better thermal responses as compared to their aqueous counterpart and reached therapeutic temperatures at faster rates due to prominent Neel relaxation mechanisms. The highest SAR value of 276.3 W/gFe is recorded for TA-ATA coated SPIONs dispersed in triethylene glycol (TEG - with high viscosity), ascribed to the lesser inter-particle interactions from electrostatic repulsions of negative charges among carboxyl/oxygen molecules from SPIONs/TEG respectively. Moreover, TA-ATA coated SPIONs have induced almost 90\% cell death in MCF-7 cancer cells in in vitro MFH studies. Thus, the TA-ATA coated SPIONs based ferrofluids have great potential for in vivo/clinical MFH cancer therapies. © 2018 Elsevier B.V.

Systematic investigations on heating effects of carboxyl-amine functionalized superparamagnetic iron oxide nanoparticles (SPIONs) based ferrofluids for in vitro cancer hyperthermia therapy

Recently superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used in cancer therapy and diagnosis (theranostics) via magnetic targeting, magnetic resonance imaging, etc. due to their remarkable magnetic properties, chemical stability, and biocompatibility. However, the magnetic properties of SPIONs are influenced by various physicochemical and synthesis parameters. So, this review mainly focuses on the influence of spin canting effects, introduced by the variations in size, shape, and organic/inorganic surface coatings, on the magnetic properties of SPIONs. This review also describes the several predominant chemical synthesis procedures and role of the synthesis parameters for monitoring the size, shape, crystallinity and composition of the SPIONs. Moreover, this review discusses about the latest developments of the inorganic materials and organic polymers for encapsulation of the SPIONs. Finally, the most recent advancements of the SPIONs and their nanopackages in combination with other imaging/therapeutic agents have been comprehensively discussed for their effective usage as in vitro and in vivo theranostic agents in cancer treatments. © 2015 Elsevier B.V. All rights reserved.