Magnetofluorescent Nanoparticles Research Articles

Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer.

The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit® enteric coating and studied under extreme conditions.

Fluorescent carbon dots tailored iron oxide nano hybrid system for in vivo optical imaging of liver fibrosis

Hybrid nanoparticles are innovative invention of last decade designed to overcome limitations of single-component nanoparticles by introducing multiple functionalities through combining two or more different nanoparticles. In this study, we are reporting development of magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbon nanoparticles to enable in vivo fluorescence imaging which also has all the required characteristic properties to use as Magnetic Resonance Imaging (MRI) contrast agent. In order to achieve dual-functional imaging, alginate and pullulan coated super paramagnetic iron oxide nanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesised separately. ASPIONs and PSPIONs were further chemically conjugated with Cdts and developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts. Subsequently, evaluation of the materials for its size, functionalisation efficiency, fluorescence and magnetic properties, biocompatibility and cellular uptake efficiency has been carried out. Fluorescence imaging of liver fibrosis was performed in vivo in rodent model of liver fibrosis using the two nanohybrids, which is further confirmed by high fluorescence signal from the harvested liver.

Bioimaging Probes Based on Magneto-Fluorescent Nanoparticles.

Novel nanomaterials are of interest in biology, medicine, and imaging applications. Multimodal fluorescent-magnetic nanoparticles demand special attention because they have the potential to be employed as diagnostic and medication-delivery tools, which, in turn, might make it easier to diagnose and treat cancer, as well as a wide variety of other disorders. The most recent advancements in the development of magneto-fluorescent nanocomposites and their applications in the biomedical field are the primary focus of this review. We describe the most current developments in synthetic methodologies and methods for the fabrication of magneto-fluorescent nanocomposites. The primary applications of multimodal magneto-fluorescent nanoparticles in biomedicine, including biological imaging, cancer treatment, and drug administration, are covered in this article, and an overview of the future possibilities for these technologies is provided.

Magneto-fluorescent contrast agents based on carbon Dots@Ferrite nanoparticles for tumor imaging

Bimodal magnetic-fluorescent materials for diagnostic imaging needs surface-engineered nanoparticles with great biosafety, pronounced colloidal stability, high magnetic moments, and strong photoluminescence (PL) emission. This work presents polymer-coated nanoparticles (PCNPs) based on manganese ferrites covered with a thin shell of nitrogen-doped carbon dots for magnetic-resonance and fluorescent dual mode imaging of cancerous tumors in vivo. An in situ thermolysis of metal oxalates and phenylenediamine in diphenyl ether allows for the facile synthesis of hybrid magneto-fluorescent nanoparticles. They possess an average size of 55 ± 5 nm with strong and excitation-independent PL emission at about 600 nm with a saturation magnetization of ∼ 19 emu/g. In vivo dispersion and biosafety of the hybrid nanoparticles are improved by a polymer-coating strategy with the aid of Tween polysorbate. In vitro studies for SK-OV-3 cells reveal that PCNPs are not toxic up to a high concentration of 125 µg/mL. H&E-stained sections of vital organs of animals treated with dosages of 5 mg/kg fail to present any histopathological changes after 24 h post-injection. The fluorescence intensity in the tumor tissue region appears to increases over time and the tumor becomes clearly visible after 60 min. Magnetic resonance imaging (MRI) of phantoms and animal cases also indicates the high efficiency of PCNPs as an T2 contrast agent in clinical diagnosis. Therefore, the developed PCNPs offer great potential for dual mode imaging of malignant tumors.

Impact of RAFT chain transfer agents on the polymeric shell density of magneto-fluorescent nanoparticles and their cellular uptake.

The impact of nanoparticle surface chemistry on cell interactions and especially cell uptake has become evident over the last few years in nanomedicine. Since PEG polymers have proved to be ideal tools for attaining stealthiness and favor escape from the in vivo mononuclear phagocytotic system, the accurate control of their geometry is of primary importance and can be achieved through reversible addition-fragmentation transfer (RAFT) polymerization. In this study, we demonstrate that the residual groups of the chain transfer agents (CTAs) introduced in the main chain exert a significant impact on the cellular internalization of functionalized nanoparticles. High-resolution magic angle spinning 1H NMR spectroscopy and fluorescence spectroscopy permitted by the magneto-fluorescence properties of nanoassemblies (NAs) revealed the compaction of the PEG comb-like shell incorporating CTAs with a long alkyl chain, without changing the overall surface potential. As a consequence of the capability of alkyl units to self-assemble at the NA surface while hardly contributing more than 0.5% to the total polyelectrolyte weight, denser PEGylated NAs showed notably less internalization in all cells of the tumor microenvironment (tumor cells, macrophages and healthy cells). Interestingly, such differentiated uptake is also observed between pro-inflammatory M1-like and immunosuppressive M2-like macrophages, with the latter more efficiently phagocytizing NAs coated with a less compact PEGylated shell. In contrast, the NA diffusion inside multicellular spheroids, used to mimic solid tumors, appeared to be independent of the NA coating. These results provide a novel effort-saving approach where the sole variation of the chemical nature of CTAs in RAFT PEGylated polymers strikingly modulate the cell uptake of nanoparticles upon the organization of their surface coating and open the pathway toward selectively addressing macrophage populations for cancer immunotherapy.

Nano-SAR Modeling for Predicting the Cytotoxicity of Metal Oxide Nanoparticles to PaCa2.

Nowadays, the impact of engineered nanoparticles (NPs) on human health and environment has aroused widespread attention. It is essential to assess and predict the biological activity, toxicity, and physicochemical properties of NPs. Computation-based methods have been developed to be efficient alternatives for understanding the negative effects of nanoparticles on the environment and human health. Here, a classification-based structure-activity relationship model for nanoparticles (nano-SAR) was developed to predict the cellular uptake of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2). The norm index descriptors were employed for describing the structure characteristics of the involved nanoparticles. The Random forest algorithm (RF), combining with the Recursive Feature Elimination (RFE) was employed to develop the nano-SAR model. The resulted model showed satisfactory statistical performance, with the accuracy (ACC) of the test set and the training set of 0.950 and 0.966, respectively, demonstrating that the model had satisfactory classification effect. The model was rigorously verified and further extensively compared with models in the literature. The proposed model could be reasonably expected to predict the cellular uptakes of nanoparticles and provide some guidance for the design and manufacture of safer nanomaterials.

Tailor made magnetic nanolights: fabrication to cancer theranostics applications.

Nanoparticles having magnetic and fluorescent properties could be considered as a gift to materials scientists due to their unique magneto-optical qualities. Multiple component particles can overcome challenges related with a single component and unveil bifunctional/multifunctional features that can enlarge their applications in diagnostic imaging agents and therapeutic delivery vehicles. Bifunctional nanoparticles that have both luminescent and magnetic features are termed as magnetic nanolights. Herein, we present recent progress of magneto-fluorescent nanoparticles (quantum dots based magnetic nanoparticles, Janus particles, and heterocrystalline fluorescent magnetic materials), comprehensively describing fabrication strategies, types, and biomedical applications. In this review, our aim is not only to encompass the preparation strategies of these special types of magneto-fluorescent nanomaterials but also their extensive applications in bioimaging techniques, cancer therapy (targeted and hyperthermic), and sustained release of active agents (drugs, proteins, antibodies, hormones, enzymes, growth factors).

Facile synthesis of magneto-fluorescent carbon dots by one-step microwave-assisted pyrolysis

Magneto-fluorescent nanoparticles have been widely designed as multifunctional materials for various advanced applications. Here, a facile approach was established to synthesize magneto-fluorescent carbon dots (MF-CDs) of approximately 2 nm by one-step microwave-assisted pyrolysis of citric acid and ethylenediamine in presence of FeCl2. The FT-IR and XRD analysis revealed the existence of iron oxides in the N-doped CDs. The magnetization analysis demonstrated the mixed phase of Fe3O4 with FeO in the MF-CDs with a saturation magnetization of 0.20 emu/g. The MF-CDs possessed the excitation-independent fluorescence with maximum PL intensity at excitation wavelength of 350 nm. The superparamagnetic and fluorescent behaviors make the designed ultrafine MF-CDs promising potential in multimodal cellular imaging.

The cytotoxicity of nanomaterials: Modeling multiple human cells uptake of functionalized magneto-fluorescent nanoparticles via nano-QSAR

The vast majority of nanomaterials have attracted an upsurge of interest since their discovery and considerable researches are being carried out about their adverse outcomes for human health and the environment. In this study, two regression-based quantitative structure-activity relationship models for nanoparticles (nano-QSAR) were established to predict the cellular uptakes of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2) and human umbilical vein endothelial cells (HUVEC) lines, respectively. The improved SMILES-based optimal descriptors encoded with certain easily available physicochemical properties were proposed to describe the molecular structure characteristics of the involved nanoparticles, and the Monte Carlo method was used for calculating the improved SMILES-based optimal descriptors. Both developed nano-QSAR models for cellular uptake prediction provided satisfactory statistical results, with the squared correlation coefficient (R2) being 0.852 and 0.905 for training sets, and 0.822 and 0.885 for test sets, respectively. Both models were rigorously validated and further extensively compared to literature models. Predominant physicochemical features responsible for cellular uptake were identified by model interpretation. The proposed models could be reasonably expected to provide guidance for synthesizing or choosing safer, more suitable surface modifiers of desired properties prior to their biomedical applications.

Systematic spectroscopic investigation of structural changes and corona formation of bovine serum albumin over magneto-fluorescent nanoparticles.

Magneto-fluorescent nanoparticles have attracted great attention because of their dual nature as multimodal imaging probes in various biomedical applications. Particulary, it is desirable to understand how these nanoparticles interact with human serum proteins before they are used in biological systems. In this work, the physiological interactions between magneto-fluorescent nanoparticles (MFNPs) and bovine serum albumin (BSA) were systematically investigated. The present observations identified that the collision of MFNPs and BSA caused fluorescence quenching of BSA. Steady state fluorescence, lifetime and anisotropy measurements in the presence of MFNPs supported dynamic quenching of the BSA emission. Furthermore, in the presence of MFNPs, the conformation changes in the BSA structure indicate merely the secondary structural changes. The findings demonstrated that random interactions and hydrophobic forces play a major role in the dynamic quenching. Further, subsequent coating of BSA over MFNPs result in protein corona formation, as is evident through spectroscopic measurements. In light of the present work, MFNPs could serve a purpose in magnetic separation and optical detection of serum proteins from blood plasma in real-time disease diagnosis.

Small, Clickable, and Monovalent Magnetofluorescent Nanoparticles Enable Mechanogenetic Regulation of Receptors in a Crowded Live-Cell Microenvironment.

Multifunctional magnetic nanoparticles have shown great promise as next-generation imaging and perturbation probes for deciphering molecular and cellular processes. As a consequence of multicomponent integration into a single nanosystem, pre-existing nanoprobes are typically large and show limited access to biological targets present in a crowded microenvironment. Here, we apply organic-phase surface PEGylation, click chemistry, and charge-based valency discrimination principles to develop compact, modular, and monovalent magnetofluorescent nanoparticles (MFNs). We show that MFNs exhibit highly efficient labeling to target receptors present in cells with a dense and thick glycocalyx layer. We use these MFNs to interrogate the E-cadherin-mediated adherens junction formation and F-actin polymerization in a three-dimensional space, demonstrating the utility as modular and versatile mechanogenetic probes in the most demanding single-cell perturbation applications.

Multifunctional Magneto-Fluorescent Nanocarriers for Dual Mode Imaging and Targeted Drug Delivery

The authors describe a novel multifunctional magneto-fluorescent MFCSNPs-FA-CHI-5FU nanocarrier that consists of magneto-fluorescent nanoparticles (MFCSNPs) targeted with folic acid (FA), modified with chitosan (CHI), and loaded with a 5-flouoruracil (5-FU) in dual mode imaging and targeted drug delivery. Multifunctional magneto-fluorescent nanocarriers show multicolor emission and superparamagnetic behavior which are advantageous for bioimaging and magnetic resonance (MR) imaging, respectively. In-vitro drug release studies show a pH-activated drug release with 92% of loaded 5-FU released in 30 h and MR imaging exhibiting excellent dose-dependent signal enhancement in T2-weighted images. This suggests that MFCSNPs-FA-CHI-5FU nanocarriers can be used as T2-weighted negative contrast agents in cancer diagnosis. In-vitro cytotoxicity and anticancer activity of the synthesized MFCSNPs-FA-CHI-5FU nanocarriers were evaluated on three cancer cell lines having different percentages of folate receptors viz. A375,...

Synergistic Anticancer Potential of Artemisinin When Loaded with 8-Hydroxyquinoline-Surface Complexed-Zinc Ferrite Magnetofluorescent Nanoparticles and Albumin Composite.

Herein, we report the fabrication of a novel class of magnetofluorescent theranostic nanoparticles (MFTNPs) based on "surface-complexation" of zinc ferrite (ZnFe2O4) NPs with 8-hydroxyquinoline. The potential of these MFTNPs in fluorescence-based bioimaging of different cancer cells was successfully demonstrated. The superparamagnetic behavior of the MFTNPs was exploited effectively in magnetic targeting in vitro. Finally, a well-known hydrophobic antimalarial and prospective anticancer drug artemisinin was efficiently loaded into MFTNPs. Artemisinin loaded MFTNPs were observed to induce superior antiproliferative response, as compared to free drug, in cancer cells in a synergistic mechanism with combination index of 0.1 or less.

Surface-Complexed Zinc Ferrite Magnetofluorescent Nanoparticles for Killing Cancer Cells and Single-Particle-Level Cellular Imaging

The fabrication of novel magnetofluorescent nanoparticles (NPs) by complexation of zinc ions present on the surface of a zinc ferrite nanoparticle (ZnFe2O4 NP) with 8-hydroxy-2-quinolinecarboxaldehyde (HQCald) is reported. The as-prepared HQCald-complexed ZnFe2O4 NPs showed good quantum yield (3.62%), high photostability, considerable excited-state lifetime (5.31 ns), and high saturation magnetization (12.7 emu/g). These magnetofluorescent NPs demonstrated bioimaging capability at both the ensemble- and single-particle levels and in vitro magnetic targeting. Moreover, the pronounced antiproliferative efficacy of these NPs against cancer cells, with appropriate targeting strategies, can lead to potential cancer theranostics.

Magneto-Fluorescent Yolk–Shell Nanoparticles

We present a new strategy for the fabrication of magneto-fluorescent nanoparticles designed for bimodal imaging. These hybrid nanostructures comprise an optically active semiconductor nanoparticle quantum dot core with tunable fluorescence, encapsulated within a hollow paramagnetic iron oxide shell that serves as an MRI contrast agent. The yolk–shell morphology enables incorporation of the semiconductor and magnetic domains into a single structure, while avoiding direct contact between them, which typically results in quenching of the desired optical fluorescence. We successfully demonstrate utilization of the ultrasmall (15 nm hydrodynamic size) magneto-fluorescent CdSe@CdS@Hollow-Fe2O3 nanoparticles for multimodal imaging of cells at the intracellular level.

Facile surface modification of nickel ferrite nanoparticles for inherent multiple fluorescence and catalytic activities

We have developed bio-compatible magneto-fluorescent NiFe2O4 nanoparticles (NPs) by modifying the surface of the NPs with Na-tartrate. The surface modified NiFe2O4 NPs are beneficial for cell imaging, wastewater treatment and therapeutics.

Magnetofluorescent Carbon Quantum Dot Decorated Multiwalled Carbon Nanotubes for Dual-Modal Targeted Imaging in Chemo-Photothermal Synergistic Therapy.

Magnetofluorescent nanoparticles with diagnostic and therapeutic functions show great promise in nanomedicine. Here, we report the magnetofluorescent carbon nanotubes (CNTs)/doxorubicin (DOX) nanocomposites and their functions act in synergetic chemo-photothermal synergistic therapy (Chemo/PTT) in cancer excision. Magnetofluorescent CNTs conjugated with a folic acid (FA-GdN@CQDs-MWCNTs) were targets for dual-modal fluorescence (FL)/magnetic resonance (MR) imaging. Experiments in vitro and in vivo identified FA-GdN@CQDs-MWCNTs with low toxicity, and good biocompatibility. Moreover, FA-GdN@CQDs-MWCNTs whose release can be fostered by pH and NIR light dual-stimuli had been proved to be available for loading DOX. Following nuclear translocations, FA-GdN@CQDs-MWCNTs were engineered to deliver DOX that targeted the nuclei. In vivo experiment indicates that the Chemo/PTT, as compared with the respective single treatment, can significantly control tumor growth. In addition, Chemo/PTT was not shown to render any appreciable toxicity. These findings suggest that the FA-GdN@CQDs-MWCNTs/DOX could function as a multifunctional platform for simultaneous FL/MR imaging, PTT therapy, and drug delivery.

Surface engineered magneto fluorescent MnFe2O4 nanoparticles in the realm of biomedical applications

In the rapidly emerging field of multifunctional nanomaterials, this article highlights the surface functionalization of MnFe2O4 nanoparticles (NPs) with tri sodiumcitrate dihydrate ligand and their efficacies in different application. The systematic spectroscopic analysis regarding UV-visible absorption and steady state fluorescence emission and excitation reveal that the citrate functionalized MnFe2O4 (C-MnFe2O4) NPs are capable of emerging multicolor fluorescence starting from blue, green to red. The magnetic measurements demonstrate that room temperature superparamagnetic nature of MnFe2O4 NPs remains unaltered after surface modification. The potential of C-MnFe2O4 nanoparticles for magnetic resonance imaging (MRI) is also unveiled in the perspective of the protein interaction. Moreover, these multifunctional C-MnFe2O4NPs exhibit excellent catalytic efficiency in the degradation of methylene blue, a water contaminant and bilirubin, a pigment responsible for jaundice.

Hydrangea-like magneto-fluorescent nanoparticles through thiol-inducing assembly

Magneto-fluorescent nanoparticles (NPs), recognized as an emerging class of materials, have drawn much attention because of their potential applications. Due to surface functionalization and thiol-metal bonds, a simple method has been put forward for fabricating hydrangea-like magneto-fluorescent Fe3O4-SH@QD NPs, through assembling thiol-modified Fe3O4 NPs with sub-size multi-layer core/shell CdSe/CdS/ZnS QDs. After a refined but controllable silane hydrolysis process, thiol-modified Fe3O4 was fabricated, resulting in Fe3O4-SH@QD NPs with QDs, while preventing the quenching of the QDs. As a result, the core Fe3O4 NPs were 18 nm in diameter, while the scattered CdSe/CdS/ZnS QDs were 7 nm in diameter. The resultant magneto-fluorescent Fe3O4-SH@QD NPs exhibit efficient fluorescence, superparamagnetism at room temperature, and rapid response to the external field, which make them ideal candidates for difunctional probes in MRI and bio-labels, targeting and photodynamic therapy, and cell tracking and separation.

Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.

We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.