Recent advancements in manganite perovskites and spinel ferrite-based magnetic nanoparticles for biomedical theranostic applications.

Recently, magnetic nanoparticles (MNPs) based on manganite perovskites (La1-xSrxMnO3 or LSMO) and/or spinel ferrites (i.e. SPFs with the formula MFe2O4; M=Co, Mg, Mn, Ni and Zn and mixed SPFs (e.g. Co-Zn, Mg-Mn, Mn-Zn and/or Ni-Zn)) have garnered great interest in magnetic hyperthermia therapy (MHT) as heat-inducing agents due to their tuneable magnetic properties including Curie temperature (T c) to generate controllable therapeutic temperatures (i.e. 42 °C-45 °C)-under the application of an alternating magnetic field (AMF)-for the treatment of cancer. In addition, these nanoparticles are also utilized in magnetic resonance imaging (MRI) as contrast-enhancing agents. However, the employment of the LSMO/SPF-based MNPs in these MHT/MRI applications is majorly influenced by their inherent properties, which are mainly tuned by the synthesis factors. Therefore, in this review article, we have systematically discussed the significant chemical methods used to synthesize the LSMO/SPF-based MNPs and their corresponding intrinsic physicochemical properties (size/shape/crystallinity/dispersibility) and/or magnetic properties (including saturation magnetization (M s)/T c). Then, we have analyzed the usage of these MNPs for the effective imaging of cancerous tumors via MRI. Finally, we have reviewed in detail the heating capability (in terms of specific absorption rate) of the LSMO/SPF-based MNPs under calorimetric/biological conditions for efficient cancer treatment via MHT. Herein, we have mainly considered the significant parameters-such as size, surface coating (nature and amount), stoichiometry, concentration and the applied AMFs (including amplitude (H) and frequency (f))-that influence the heat induction ability of these MNPs.

Single and Dual Surfactants Coated Hydrophilic Superparamagnetic Iron Oxide Nanoparticles for Magnetic Fluid Hyperthermia Applications.

Superparamagnetic iron oxide nanoparticles (SPIONs) have found applications in the magnetic fluid hyperthermia (MFH) due to their unique magnetic properties, chemical stability and biocompatibility. However, challenges exist in attaining high heating efficiencies of the SPIONs under the applied alternating magnetic fields below Hergt's biological safety limit. Here, we present synthesis of single surfactant (pyromellitic acid (PMA)/2-aminoterephthalic acid (ATA)) and dual surfactants (PMA-ATA) coated SPIONs via chemical co-precipitation method and characterization to determine their phase purity, surface coatings and particle sizes. The hydrodynamic sizes/zeta potentials values of the SPIONs were determined for studying their water-dispersibility. Finally, the impact of heating on specific absorption rate (SAR) and intrinsic loss of power (ILP) were determined. SPIONs were found to exhibit magnetite phase and particle sizes in the range of 9-10 nm, good water dispersibility with (i) hydrodynamic diameters ranging from 190-304 nm and (ii) zeta potentials ranging from -38 mV to -49 mV. The ATA and PMA-ATA coated SPIONs showed better time-dependent temperature rise that resulted in higher heating efficacies-i.e., SAR and ILP values ranging from 58.6-79.5 W/gFe and 1.7-2.3 nHm²/Kg, respectively as compared to the PMA coated SPIONs. Thus, ATA and PMA-ATA coated SPIONs were found to be very promising candidates for their usage in MFH applications.

Inorganic nanocarriers for siRNA delivery for cancer treatments.

RNA interference is one of the emerging methodologies utilized in the treatment of a wide variety of diseases including cancer. This method specifically uses therapeutic RNAs (TpRNAs) like small interfering RNAs (siRNAs) to regulate/silence the cancer-linked genes, thereby minimizing the distinct activities of the cancer cells while aiding in their apoptosis. But, many complications arise during the transport/delivery of these TpRNAs that include poor systemic circulation, instability/degradation inside the body environment, no targeting capacity and also low cellular internalization. These difficulties can be overcome by using nanocarriers to deliver the TpRNAs inside the cancer cells. The following are the various categories of nanocarriers-viral vectors (e.g. lentivirus and adenovirus) and non-viral nanocarriers (self-assembling nanocarriers and inorganic nanocarriers). Viral vectors suffer from disadvantages like high immunogenicity compared to the non-viral nanocarriers. Among non-viral nanocarriers, inorganic nanocarriers gained significant attention as their inherent properties (like magnetic properties) can aid in the effective cellular delivery of the TpRNAs. Most of the prior reports have discussed about the delivery of TpRNAs through self-assembling nanocarriers; however very few have reviewed about their delivery using the inorganic nanoparticles. Therefore, in this review, we have mainly focussed on the delivery of TpRNAs-i.e. siRNA, especially programmed death ligand-1 (PD-L1), survivin, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor and other siRNAs using the inorganic nanoparticles-mainly magnetic, metal and silica nanoparticles. Moreover, we have also discussed about the combined delivery of these TpRNAs along with chemotherapeutic drugs (mainly doxorubicin) andin vitroandin vivotherapeutic effectiveness.

Current advancements in self-assembling nanocarriers-based siRNA delivery for cancer therapy.

Different therapeutic practices for treating cancers have significantly evolved to compensate and/or overcome the failures in conventional methodologies. The demonstrated potentiality in completely inhibiting the tumors and in preventing cancer relapse has made nucleic acids therapy (NAT)/gene therapy as an attractive practice. This has been made possible because NAT-based cancer treatments are highly focused on the fundamental mechanisms - i.e., silencing the expression of oncogenic genes responsible for producing abnormal proteins (via messenger RNAs (mRNAs)). However, the future clinical translation of NAT is majorly dependent upon the effective delivery of the exogenous nucleic acids (especially RNAs - e.g., short interfering RNAs (siRNAs) - herein called biological drugs). Moreover, nano-based vehicles (i.e., nanocarriers) are involved in delivering them to prevent degradation and undesired bioaccumulation while enhancing the stability of siRNAs. Herein, we have initially discussed about three major types of self-assembling nanocarriers (liposomes, polymeric nanoparticles and exosomes). Later, we have majorly reviewed recent developments in non-targeted/targeted nanocarriers for delivery of biological drugs (individual/dual) to silence the most important genes/mRNAs accountable for inducing protein abnormality. These proteins include polo-like kinase 1 (PLK1), survivin, vascular endothelial growth factor (VEGF), B-cell lymphoma/leukaemia-2 (Bcl-2) and multi-drug resistance (MDR). Besides, the consequent therapeutic effects on cancer growth, invasion and/or metastasis have also been discussed. Finally, we have comprehensively reviewed the improvements achieved in the cutting-edge cancer therapeutics while delivering siRNAs in combination with clinically approved chemotherapeutic drugs.

State-of-the-art: MXene structures in nano-oncology.

Cancer nanomedicine has been investigated widely and boomed in the last two decades, resulting in designing nanostructures with biofunctionalization, giving rise to an "All-in-One" multifunctional platform. The development of rational design technology with extended functionalities brought interdisciplinary researchers to work continuously, aiming to find a prevent or effectively treat the deadly disease of the century. Thus, it led to some Food and Drug Administration (FDA)-approving nano-based formulations for cancer treatment and opening a vast area of promising discoveries by exploiting different nanomaterials. Two-dimensional (2D) materials have recently gained tremendous interest among scientists because of their outstanding structural, optical, electronic, thermal, and mechanical characteristics. Among various 2D nanomaterials, MXenes are a widely studied nanosystem because of their close similarity to graphene analogs. So, it is synthesized using multiple approaches and exploits their inherited properties. But in most cases, surface functionalization techniques are carried out for targeting, site-specific drug clearance, renal clearance, and biocompatible with healthy cells. Thus, fabricating a multimodal agent for mono or combined therapies is also an image-guided diagnostic agent. This review will explain the recent and emerging advancements of MXenes-based composites as a multifunctional theragnostic agent and discuss the possibilities of transferring laboratory research to clinical translation.

Multifunctional theranostic nanoparticles for biomedical cancer treatments - A comprehensive review.

Modern-day search for the novel agents (their preparation and consequent implementation) to effectively treat the cancer is mainly fuelled by the historical failure of the conventional treatment modalities. Apart from that, the complexities such as higher rate of cell mutations, variable tumor microenvironment, patient-specific disparities, and the evolving nature of cancers have made this search much stronger in the latest times. As a result of this, in about two decades, the theranostic nanoparticles (TNPs) - i.e., nanoparticles that integrate therapeutic and diagnostic characteristics - have been developed. The examples for TNPs include mesoporous silica nanoparticles, luminescence nanoparticles, carbon-based nanomaterials, metal nanoparticles, and magnetic nanoparticles. These TNPs have emerged as single and powerful cancer-treating multifunctional nanoplatforms, as they widely provide the necessary functionalities to overcome the previous/conventional limitations including lack of the site-specific delivery of anti-cancer drugs, and real-time continuous monitoring of the target cancer sites while performing therapeutic actions. This has been mainly possible due to the association of the as-developed TNPs with the already-available unique diagnostic (e.g., luminescence, photoacoustic, and magnetic resonance imaging) and therapeutic (e.g., photothermal, photodynamic, hyperthermia therapy) modalities in the biomedical field. In this review, we have discussed in detail about the recent developments on the aforementioned important TNPs without/with targeting ability (i.e., attaching them with ligands or tumor-specific antibodies) and also the strategies that are implemented to increase their tumor accumulation and to enhance their theranostic efficacies for effective biomedical cancer treatments.

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

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.

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

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.

Recent advances in superparamagnetic iron oxide nanoparticles (SPIONs) for in vitro and in vivo cancer nanotheranostics.

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.