Magnetic iron oxide nanoparticles@lecithin/poly (l-lactic acid) microspheres for targeted drug release in cancer therapy.

The use of targeted chemotherapy is a promising solution to mitigate the side effects and dosage of drugs. This research focuses on the development of magnetic microspheres (MMS) based drug carriers for targeted chemotherapy, formulated with iron oxide nanoparticles (Fe3O4 NPs) and poly (l-lactic acid) (PLA) loaded with the antibiotic drug Ciprofloxacin (CIF). In this study, Fe3O4 NPs were synthesized using pomegranate peel extract as a natural reducing and stabilizing agent. The double emulsification method (W1/O/W2) was employed to produce Fe3O4@LEC-CIF-PLA-MMS, which were characterized using various spectral and microscopic techniques. The drug encapsulation efficiency for Fe3O4@LEC-CIF-PLA-MMS was found to be 80.7 %. The in vitro drug release of CIF from Fe3O4@LEC-CIF-PLA-MMS induced by H2O2 and GSH- stimuli was found to be 87.55 % and 82.32 %, respectively in acidic pH 4.5. Notably, the magnetically triggered drug release behaviour of Fe3O4@LEC-CIF-PLA-MMS (93.56 %) was assessed in acidic pH environment upon exposure to low-frequency alternating magnetic field (LF-AMF). Fe3O4@LEC-CIF-PLA-MMS demonstrated significantly enhanced in vitro cytotoxicity (IC50 = 0.8 ± 0.03 µg/mL) against the HeLa-S3 cancer cell lines. Nevertheless, these research findings highlight the potential of Fe3O4@LEC-CIF-PLA-MMS for further development as a chemotherapeutic agent and hold promise for the future of targeted cancer treatment.

ROS-Responsive Chitosan Coated Magnetic Iron Oxide Nanoparticles as Potential Vehicles for Targeted Drug Delivery in Cancer Therapy.

BACKGROUND AND OBJECTIVE: Cancer cells accumulate high concentrations of reactive oxygen species as a result of their faster and uninhibited metabolic activity. Cancer chemotherapeutic agents release an excess of severe adverse reactions as a result of targeting normal cells. This demands an improvement in targeted drug-delivery systems to selectively discharge anticancer drugs in the vicinity of such highly metabolically and mitotically active cells. MATERIALS AND METHODS: Here, magnetic nanoparticles were synthesized by a traditional co-precipitation technique. Fe3O4@OA-CS-5-FLU-NPs were synthesized by an easy and rapid in situ loading method. The proposed Fe3O4@OA-CS-5-FLU-NPs were productively prepared as well as characterized by various spectroscopic and microscopic studies. RESULTS: The targeted drug release profile of the Fe3O4@OA-CS-5-FLU-NPs was studied in the presence of ROS including H2O2 and pH induction. The released product, Fe3O4@OA-CS-5-FLU-NP, exhibited desirable levels of cytotoxicity and demonstrated morphological changes and inhibition of colony formation for A549 and HeLa S3 cancer cells. The IC50 values at 24 hours were 12.9 and 23 µg/mL, respectively. CONCLUSION: In summary, results from the MTT assay, fluorescence staining as well as colony formation assays, revealed that the Fe3O4@OA-CS-5-FLU-NPs were active and safe for anticancer biomedical applications. In summary, the present investigation provides a powerful nanostructured based system for improved cancer theranostics that should be further studied.

Bidentate Schiff Base Ligands Appended Metal(II) Complexes as Probes of DNA and Plasma Protein: In Silico Molecular Modelling Studies.

HL1 and HL2 (HL1 = 5-diethylamino-2-({[4-(diethylamino)phenyl]imino}methyl)-phenol; HL2 = 5-diethylamino-2-({[4-(dimethylamino)phenyl]imino}methyl)-phenol) are new Schiff base ligands which were prepared along with their metal(II) complexes of [Cu(L1)2] (1), [Cu(L1)2] (2), [Ni(L2)2] (3) and [Ni(L2)2] (4) and characterized by different analytical as well as spectroscopic analyses. The single crystal XRD analysis confirms the proposed structure of ligands such as HL1 and HL2. EPR spectral analysis gives evidence about the tetrahedrally coordinated geometry of complexes 1 and 2. Density functional theory (DFT) analysis was executed using B3LYP/6-31G(d,p)∪LanL2DZ level. The DNA sequence (along with Dickerson's sequence) specificity of complexes 1-4 was evaluated and it has resulted that the complexes 1-4 primarily interact with double helix of DNA via groove mode of binding. From plasma protein docking results, we can say that complexes 2 and 4 showed more binding towards HSA and may have good bioavailability and are prone to act as drug candidates. The observed findings show that these metal(II) complexes 1-4 are better DNA probes, will act as anticancer agents and stimulate strong research focusing on the design of new chemical probes of DNA.

Biological Impacts of Metal(II) Complex-Based DNA Probes Derived from Bidentate N,O Donor Schiff Base Ligand.

In this article, we have reported the preparation and structural characterization of a new Schiff base ligand (E)-2-(((2,6-difluorophenyl)imino)methyl)phenol (HSBL) and its derived metal(II) complexes [Cu(SBL)2] (1), [Ni(SBL)2] (2) and [Pd(SBL)2] (3). Using various analytical and spectroscopic techniques, their structural properties have been appraised. The proposed chemical structure of HSBL has been confirmed by Single crystal XRD studies. Bidentate characteristic of HSBL and its coordination with metal(II) ions through the oxygen atom of the phenolic group and nitrogen atom of the azomethine group have been evaluated from the FT-IR spectral analysis. Pd(II) complex of HSBL (complex 3) has found to be efficient in bringing about the interaction with DNA as well as BSA molecules. The in vitro antimicrobial studies have been demonstrated that complex 3 has a superior antimicrobial activity than HSBL, complexes 1 and 2. According to the values of zone of inhibition, the antimicrobial ability has been increased in the order of 3 > 1 > 2 > HSBL. A significant decrease in percent cell viability has been suggested that complex 3 has remarkable cytotoxicity (IC50 = 15.7 ± 0.6 µg/mL) on human breast cancer (MCF-7) cells. Besides, their induced apoptosis pathway of cytotoxicity has been demonstrated by fluorescence staining techniques using AO/EB staining method. We hope this article will be very helpful for future research on the development of new anticancer agents.

Iron oxide nanoparticle core-shell magnetic microspheres: Applications toward targeted drug delivery.

This study describes a sensitive reactive oxygen species (ROS)-responsive lecithin (LEC) incorporated iron oxide nanoparticle (Fe3O4 NP) system with potent anti-inflammatory properties and even more so when the antioxidant drug curcumin (CUR) is encapsulated in the PLGA hybrid magnetic microsphere system (Fe3O4@LEC-CUR-PLGA-MMS). The delivery system is responsive to ROS including an H2O2 environment to release the payload (CUR) drug. Greater cytotoxicity properties were observed in the presence of Fe3O4@LEC-CUR-PLGA-MMS against A549 and HeLa S3 cells with IC50 values after 24 h of 10 and 12 µg/mL and 10 and 20 µg/mL, respectively. The present Fe3O4@LEC-CUR-PLGA-MMS system demonstrated much better in vitro cytotoxicity, cellular morphological changes and moreover an ability to limit colony formation for A549 and HeLa S3 cancer cell lines than non-cancerous cells, and thus, should be further studied for a wide range of medical applications.

Crystal structure, optical properties, DFT analysis of new morpholine based Schiff base ligands and their copper(II) complexes: DNA, protein docking analyses, antibacterial study and anticancer evaluation.

New morpholine derived Schiff base ligands (HL1 and HL2) and their Cu(II) complexes [Cu(L1)2] (1) and [Cu(L2)2] (2) have been synthesized and characterized by 1H NMR, IR, UV-Vis, EPR studies and cyclic voltammetric analyses. Single crystal X-ray crystallography studies confirm the structure of newly synthesized Schiff base ligands HL1and HL2. The ground state electronic structures of Cu(II) complexes 1 and 2 have been investigated by DFT/B3LYP theoretical analysis with 6-31G (d,p) and LANL2DZ basis set. The affinity towards DNA and protein molecules have been evaluated using computational docking analysis and complex 2 expose significant binding ability with DNA as well as protein due to its towering hydrophobicity. Consequently, complex 2 reveals superior antibacterial activity against some bacterial species besides anticancer activity on human breast cancer (MCF-7) cells than complex 1 and Schiff base ligands (HL1 and HL2). These preliminary investigations strongly recommended that complex 2 can be used as a better antibacterial plus anticancer agent.

Multispectroscopic and bioimaging approach for the interaction of rhodamine 6G capped gold nanoparticles with bovine serum albumin.

Binding interaction of Bovine Serum Albumin (BSA) with newly prepared rhodamine 6G-capped gold nanoparticles (Rh6G-Au NPs) under physiological conditions (pH 7.2) was investigated by a wide range of photophysical techniques. Rh6G-Au NPs caused the static quenching of the intrinsic fluorescence of BSA that resulted from the formation of ground-state complex between BSA and Rh6G-Au NPs. The binding constant from fluorescence quenching method (Ka = 1.04 × 104 L mol-1; LoD = 14.0 µM) is in accordance with apparent association constant (Kapp = 1.14 × 101 M-1), which is obtained from absorption spectral studies. Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residue of BSA and fluorophore of Rh6G-Au NPs during the interaction was calculated to be 90%. The free energy change (ΔG = -23.07 kJ/mol) of BSA-Rh6G-Au NPs complex was calculated based on modified Stern-Volmer Plot. The time-resolved fluorescence analysis confirmed that quenching of BSA follows static mechanism through the formation of ground state complex. Furthermore, synchronous and three-dimensional fluorescence measurement, Raman spectral analysis and Circular Dichroism spectrum results corroborate the strong binding between Rh6G-Au NPs and BSA, which causes the conformational changes on BSA molecule. In addition, fluorescence imaging experiments of BSA in living human breast cancer (HeLa) cells was successfully demonstrated, which articulated the value of Rh6G-Au NPs practical applications in biological systems.

A theranostic nanocomposite system based on iron oxide-drug nanocages for targeted magnetic field responsive chemotherapy.

In this work, a theranostic nanocage system was developed for the targeted delivery of the anti-cancer agents camptothecin (CPT) and luotonin A (LuA). The core of the nanocage system (Fe3O4@OA-AD-SP NCs) was formed by biogenically synthesized Fe3O4 nanoparticles (NPs) decorated with a model anti-cancer drug (AD) and biosurfactant saponin (SP). The Fe3O4@OA-AD-SP NCs showed a high lipophilic AD loading efficiency (>80%) and a controlled pH-responsive drug release in stimulated cancerous cells in pH 6.4 media buffer. In addition, Fe3O4@OA-AD-SP NCs exhibited better serum protein binding efficacy at physiological pH values (7.4), furthering the important role of SP surface decoration. Particularly, these NCs showed better chemotherapeutic efficacy when examined in MCF-7 and HeLa cancer cell lines with a specific targeting capacity. Therefore, this study provides a new nano platform based on magnetic targeting and pH responsive lipophilic anticancer drug delivery to the cancer site.

Magnetic iron oxide nanoparticles (MIONs) cross-linked natural polymer-based hybrid gel beads: Controlled nano anti-TB drug delivery application.

The nanosized rifampicin (RIF) has been prepared to increase the solubility in aqueous solution, which leads to remarkable enhancement of its bioavailability and their convenient delivery system studied by newly produced nontoxic, biodegradable magnetic iron oxide nanoparticles (MIONs) cross-linked polyethylene glycol hybrid chitosan (mCS-PEG) gel beads. The functionalization of both nano RIF and mCS-PEG gel beads were studied using various spectroscopic and microscopic techniques. The size of prepared nano RIF was found to be 70.20 ± 3.50 nm. The mechanical stability and swelling ratio of the magnetic gel beads increased by the addition of PEG with a maximum swelling ratio of 38.67 ± 0.29 g/g. Interestingly, this magnetic gel bead has dual responsive assets in the nano drug delivery application (pH and the magnetic field). As we expected, magnetic gel beads show higher nano drug releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 71.00 ± 0.87%. This efficacy may also be tuned by altering the external magnetic field and the weight percentage (wt%) of PEG. These results suggest that such a dual responsive magnetic gel beads can be used as a potential system in the nano drug delivery applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1039-1050, 2018.

One pot synthesis of new poly(vinyl alcohol) blended natural polymer based magnetic hydrogel beads: Controlled natural anticancer alkaloid delivery system.

Facile one-pot synthesis has been demonstrated for new biocompatible and dual responsive magnetic iron oxide nanoparticles cross-linked poly(vinyl alcohol) (PVA) blended natural polymer chitosan (CS) based hydrogel beads (mCS-PVA) as a controlled natural anticancer alkaloid Luotonin A (LuA) delivery system. The prepared magnetic hydrogel beads were characterized using powder X-ray diffraction measurement, Fourier transform-infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and vibrating sample magnetometer. The magnetic hydrogel beads are exhibited significant water retention and follow the second order kinetic model in swelling study. The swelling ratio of the magnetic gel beads increased by the addition of PVA and showed a maximum swelling ratio of 40.83 ± 1.01 g/g and follows non-Fickian water transport mechanism. Stimuli responsive mCS and mCS-PVA hydrogel beads functionalized with LuA is demonstrated for controlled release at physiological pH and under magnetic field. The magnetic hydrogel beads show highest LuA releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 73.33 ± 1.44%. This efficacy may also be tuned by altering the external magnetic field as well as the weight percentage (wt %) of polyethylene glycol. It is clearly that the newly produced magnetic hydrogel beads can be served as an effective intestinal LuA delivery system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 543-551, 2018.

Natural alkaloid Luotonin A and its affixed acceptor molecules: Serum albumin binding studies.

Effective interaction of natural alkaloid Luotonin A (L) and its affixed acceptor molecules 1 and 2 with donor molecule as Bovine serum albumin (BSA) at various pH (4.0, 7.4 and 10.0) medium have been demonstrated using various conventional spectroscopic techniques. These analyses provide some valuable features on the interaction between BSA and acceptor molecules (L, 1 and 2). From the absorption and fluorescence spectral titration studies, the formation of ground-state complexes between the acceptor molecules (L, 1 and 2) and the BSA have been confirmed. The results of the afore titrations analysis reveal that, the strong binding of receptor 1 with BSA (Kapp 5.68×104M-1; KSV 1.86×106Lmol-1; Ka 6.42×105Lmol-1; Kass 8.09×106M-1; ΔG -33.35kJ/mol) at physiological pH medium (7.4) than other receptor molecules 2 and L. The Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residues of BSA and acceptor molecules L, 1 and 2 during the interaction, are 28.85, 85.24 and 53.25 % respectively. The superior binding efficacy of acceptor 1 at physiological pH condition has been further confirmed by FT-IR and Raman spectral analysis methods. Moreover, theoretical docking studies of acceptors L, 1 and 2 towards HSA have been demonstrated to differentiate their binding behaviours. It reveals that, acceptor 1 has the strongest binding ability with HSA through two hydrogen bonding and the Atomic contact energy (ACE) value of -483.96kcal/mol.

Non-enolisable Knoevenagel condensate appended Schiff bases-metal (II) complexes: Spectral characteristics, DNA-binding and nuclease activities.

New Schiff base complexes [Cu(L1)Cl] (1), [Ni(L1)Cl] (2), [Zn(L1)Cl] (3), and [Fe(L2)H2OCl] (4) {L1=(4E)-3-(2-hydroxybenzylidene)-4-(2-hydroxyphenylimino)pentan-2-one, L2=2,2'-(1E,1'E)-(3-(2-hydroxybenzylidene)-pentane-2,4-diylidene)bis(azan-1-yl-1 idene)diphenol} have been synthesized and characterized by elemental analysis, UV-Vis, IR, FAB-mass, EPR, spectral studies and electrochemical studies, the ligands L1 &L2 were characterized by 1H and 13C NMR spectra. Complex 1 show a visible spectral d-d band near 600nm and display cyclic voltammetric quasireversible response for the Cu(II)/Cu(I) couple vs Ag/AgCl in DMSO. The EPR spectrum of 1 show g‖>g⊥ suggesting a square planar geometry around copper with dx2-y2 as the ground state. The mass spectral results have confirmed the proposed structure for complexes 1-4. DNA binding properties of these complexes 1-4 have been investigated by absorption titrations, cyclic voltammetric studies and circular dichroism studies. On titration with DNA, the complexes 1-4 show hypochromism at the MLCT band (13-31%) with a red shift of 1-8nm in the electronic spectrum and positive shift of voltammetric E1/2 in the CV studies are in favour of intercalative binding. CD spectra of 1 showed an increase in molar ellipticity (θ278) of the positive band with a minor red shift indicating the transition of B-form of DNA to A like form. DNA cleavage studies of complexes 1 and 4 with pUC18 DNA were studied by gel electrophoresis and complex 4 cleaves supercoiled pUC18 DNA in an oxidative manner in the presence of H2O2 and on photo irradiation at 312nm.