Herein, flower-shaped hydrophilic superparamagnetic iron oxide nanoclusters (IONCs) are synthesized via one-pot thermolysis of iron acetylacetonate using triethanolamine (TEA) and diethylene glycol (DEG)/tetraethylene glycol (TTEG) mixtures at 9:1, 8:2 and 7:3 (v/v) ratios. The as-prepared 24–29 nm sized IONCs have displayed (i) saturation magnetization (Ms) values of ~68–78 emu/g, (ii) hydrodynamic diameters of ~95–192 nm and (iii) zeta potential values of +46 to +65 mV. Due to relatively high magnetization and water solubility, IONCs (prepared using 8:2 TEA:DEG, and 8:2 &amp; 7:3 TEA:TTEG ratios) based aqueous ferrofluids i.e. NCAFF-1, NCAFF-2, and NCAFF-3 are investigated by calorimetric magnetic fluid hyperthermia (MFH) at 0.5–8 mg/ml concentrations by exposing them to the alternating magnetic fields (AMFs, H*f ~2.4–9.9 GA m−1 s−1). The NCAFF-3 has demonstrated excellent time dependent temperature rise (42 °C within 0.7–9.7 min) as compared to the NCAFF-1 and NCAFF-2. Moreover, the NCAFF-3 at 0.5 mg/ml concentration has exhibited enhanced heating efficacies with specific absorption rate (SAR) and intrinsic loss power (ILP) values of 142.4–909.4 W/gFe and 4.2–14.7 nHm2/kg, respectively. Furthermore, the NCAFF-3 has presented better cytocompatibility, and substantially reduced proliferation capacity of HepG2 cancer cells in in vitro MFH studies. Thus, the IONCs based ferrofluids (NCAFF-3) are very promising candidates for MFH therapeutics applications. © 2018 Elsevier B.V.

Naga Suresh Veerapu

Life Sciences

(SoNS) School of Natural Sciences

Kandasamy G.

Khan S.

Giri J.

Bose S.

Maity D.

Fulltext

<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

Journal of Molecular Liquids

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

In the last few decades, superparamagnetic iron oxide nanoparticles (SPIONs—particularly magnetite (Fe3O4)/maghemite (Fe2O3) nanoparticles) have gained a great deal of attention in many biomedical applications, including magnetic targeting based cell isolation/sorting, tissue engineering, gene delivery, and magnetofection, due to their unique magnetic properties, excellent chemical stability, biodegradability, and low toxicity as compared to other magnetic materials (for instance, Co, Mn, and Ni). But recently, SPIONs (in the form of ferrofluids—i.e., SPIONs dispersed in a carrier fluid) have become a highly promising candidate for their use as therapeutic and diagnostic (theranostic) agents in cancer treatment applications such as magnetic fluid hyperthermia (MFH) and magnetic resonance imaging (MRI), respectively. However, the theranostic efficacies of the SPIONs (or ferrofluids) might alter due to the differences in their physicochemical/dispersibility/magnetic properties that are significantly impacted by their synthesis methods and their stabilization process. In this chapter, we have initially discussed the crystal structure/composition and different synthesis methods of the SPIONs. Then, we have described the role of the SPIONs in the formation of the ferrofluids along with their stabilization process via diverse interactions. Finally, we have discussed about their (1) intrinsic cancer theranostic applications of SPIONs such as magnetic fluid hyperthermia, magnetic resonance imaging, and magnetic nanoparticle-based drug delivery and (2) combined cancer theranostics applications including MRI as an adjuvant to fluorescence imaging, thermo-chemotherapy, thermo-radiotherapy, and thermo-immunotherapy. © Springer Nature Switzerland AG 2019. All rights reserved.

Nanotheranostics: Applications and Limitations

Superparamagnetic iron oxide nanoparticles for cancer theranostic applications

In this work, we report the synthesis of hydrophilic and surface-functionalized superparamagnetic iron oxide nanoparticles (SPIOs) to utilize them as nanomedicines for treating liver cancer via magnetic fluid hyperthermia (MFH)-based thermotherapy. For this purpose, initially, we have synthesized the SPIOs through co-precipitation/thermolysis methods, followed by in situ surface functionalization with short-chained molecules, such as 1,4-diaminobenzene (14DAB), 4-aminobenzoic acid (4ABA) and 3,4-diaminobenzoic acid (34DABA) and their combination with terephthalic acid (TA)/2-aminoterephthalic acid (ATA)/trimesic acid (TMA)/pyromellitic acid (PMA) molecules. The as-prepared SPIOs are investigated for their structure, morphology, water dispersibility, and magnetic properties. The heating efficacies of the SPIOs are studied in calorimetric MFH (C-MFH) with respect to their concentrations, surface coatings, dispersion medium, and applied alternating magnetic fields (AMFs). Although all of the as-prepared SPIOs have exhibited superparamagnetic behavior, only 14DAB-, 4ABA-, 34DABA-, and 4ABA-TA-coated SPIOs have shown higher magnetization values (Ms = 55-71 emu g-1) and good water dispersibility. In C-MFH studies, 34DABA-coated SPIO-based aqueous ferrofluid (AFF) has revealed faster thermal response to the applied AMF and reached therapeutic temperature even at the lowest concentration (0.5 mg mL-1) compared with 14DAB-, 4ABA-, and 4ABA-TA-coated SPIO-based AFFs. Moreover, 34DABA-coated SPIO-based AFF has exhibited high heating efficacies (i.e., specific absorption rate/intrinsic loss power values of 432.1 W gFe-1/5.2 nHm2 kg-1 at 0.5 mg mL-1), which could be mainly due to (i) enhanced π-π conjugation paths of surface-attached 34DABA coating molecules because of intrafunctional group attractions and (ii) improved anisotropy from the formation of clusters/linear chains of the SPIOs in ferrofluid suspensions, owing to interfunctional group attractions/interparticle interactions. Moreover, the 34DABA-coated SPIOs have demonstrated (i) very good cytocompatibility for 24/48 h incubation periods and (ii) higher killing efficiency of 61-88\% (via MFH) in HepG2 liver cancer cells as compared to their treatment with only AMF/water-bath-based thermotherapy. In summary, the 34DABA-coated SPIOs are very promising heat-inducing agents for MFH-based thermotherapy and thus could be used as effective nanomedicines for cancer treatments. © 2018 American Chemical Society.

ACS Omega

Functionalized Hydrophilic Superparamagnetic Iron Oxide Nanoparticles for Magnetic Fluid Hyperthermia Application in Liver Cancer Treatment

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

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

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.