RESUMEN
Metal-free near-infrared absorbing photosensitizers (PS) have been considered promising candidates for photodynamic therapy. Curcumin, curcuminoid, and its derivatives have therapeutic values due to their anti-inflammatory, antifungal, and antiproliferative properties. Curcuminoid-BF2 chelates have also been studied as cell imaging probes, however, their applications in photodynamic therapy are rare. In this article, we describe the synthesis and therapeutic evaluation of quinolizidine fused curcuminoid-BF2 chelate (Quinolizidine CUR-BF2) containing an acid-sensitive group. This donor-acceptor-donor curcuminoid-BF2 derivative exhibits absorption and emission in the deep red region with an absorption band maximum of â¼647 nm and a weak emission band at approximately 713 nm. It is interesting to note that this derivative has a high molar extinction coefficient (164,655 M-1cm-1). Quinolizidine CUR-BF2 possesses intramolecular charge transfer properties, facilitating the production of singlet oxygen (1O2), which plays a crucial role in cell death. Additionally, Quinolizidine CUR-BF2 can enable the selective release of active ingredients in an acidic medium (pH 5). Furthermore, the nanoaggregates of PS were prepared by encapsulating Quinolizidine CUR-BF2 within Pluronic F127 block co-polymer for better water-dispersibility and enhanced cellular uptake. Dark cytotoxicity of nanoaggregates was found to be negligible, whereas they exhibited significant photoinduced cytotoxicity towards cancer cells (MCF-7 and A549) under irradiation of 635 nm light. Further, the cell death pathway using Quinolizidine CUR-BF2 nanoaggregates as PS is found to occur through apoptosis. Specifically, the present study deals with the successful preparation of Quinolizidine CUR-BF2 nanoaggregates for enhanced water-dispersibility and cellular uptake as well as the efficacy evaluation of developed nanoaggregates for photodynamic therapy.
Asunto(s)
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Diarilheptanoides , Células A549 , Células MCF-7 , Fármacos Fotosensibilizantes/farmacología , AguaRESUMEN
We report a facile approach for the preparation of protein conjugated glutaric acid functionalized Fe3O4 magnetic nanoparticles (Pro-Glu-MNPs), having improved colloidal stability and heating efficacy. The Pro-Glu-MNPs were prepared by covalent conjugation of BSA protein onto the surface of glutaric acid functionalized Fe3O4 magnetic nanoparticles (Glu-MNPs) obtained through thermal decomposition. XRD and TEM analyses confirmed the formation of crystalline Fe3O4 nanoparticles of average size ~5 nm, whereas the conjugation of BSA protein to them was evident from XPS, FTIR, TGA, DLS and zeta-potential measurements. These Pro-Glu-MNPs showed good colloidal stability in different media (water, phosphate buffer saline, cell culture medium) and exhibited room temperature superparamagnetism with good magnetic field responsivity towards the external magnet. The induction heating studies revealed that the heating efficacy of these Pro-Glu-MNPs was strongly reliant on the particle concentration and their stabilizing media. In addition, they showed enhanced heating efficacy over Glu-MNPs as surface passivation by protein offers colloidal stability to them as well as prevents their aggregation under AC magnetic field. Further, Pro-Glu-MNPs are biocompatible towards normal cells and showed substantial cellular internalization in cancerous cells, suggesting their potential application in hyperthermia therapy.
Asunto(s)
Hipertermia Inducida/métodos , Nanopartículas Magnéticas de Óxido de Hierro/química , Nanoconjugados/química , Albúmina Sérica Bovina/química , Glutaratos/química , Células HeLa , Humanos , Células MCF-7 , Estabilidad ProteicaRESUMEN
Magnetic luminescent hybrid nanostructures (MLHN) have received a great deal of attention due to their potential biomedical applications such as thermal therapy, magnetic resonance imaging, drug delivery and intracellular imaging. We report the development of bifunctional Fe3O4 decorated YPO4:Eu hybrid nanostructures by covalent bridging of carboxyl PEGylated Fe3O4 and amine functionalized YPO4:Eu particles. The surface functionalization of individual nanoparticulates as well as their successful conjugation was evident from Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential and transmission electron microscopy (TEM) studies. X-ray diffraction (XRD) analysis reveals the formation of highly crystalline hybrid nanostructures. TEM micrographs clearly show the binding/anchoring of 10 nm Fe3O4 nanoparticles onto the surface of 100-150 nm rice grain shaped YPO4:Eu nanostructures. These MLHN show good colloidal stability, magnetic field responsivity and self-heating capacity under an external AC magnetic field. The induction heating studies confirmed localized heating of MLHN under an AC magnetic field with a high specific absorption rate. Photoluminescence spectroscopy and fluorescence microscopy results show optical imaging capability of MLHN. Furthermore, successful internalization of these MLHN in the cells and their cellular imaging ability are confirmed from confocal microscopy imaging. Specifically, the hybrid nanostructure provides an excellent platform to integrate luminescent and magnetic materials into one single entity that can be used as a potential tool for hyperthermia treatment of cancer and cellular imaging.
Asunto(s)
Europio/química , Óxido Ferrosoférrico/química , Sustancias Luminiscentes/química , Nanoestructuras/química , Fosfatos/química , Itrio/química , Línea Celular Tumoral , Europio/uso terapéutico , Óxido Ferrosoférrico/uso terapéutico , Humanos , Hipertermia Inducida , Sustancias Luminiscentes/uso terapéutico , Campos Magnéticos , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Nanoestructuras/uso terapéutico , Nanoestructuras/ultraestructura , Neoplasias/diagnóstico , Neoplasias/terapia , Imagen Óptica , Itrio/uso terapéuticoRESUMEN
Superparamagnetic Fe3O4 nanoparticles are appealing materials for heat activated killing of cancer cells. Here, we report a novel method to enhance the heat activated killing of cancer cells under an AC magnetic field (AMF) by introducing a polyaniline impregnated shell onto the surface of Fe3O4 nanoparticles. These polyaniline shell cross-linked magnetic nanoparticles (PSMN) were prepared by in situ polymerization of aniline hydrochloride on the surface of carboxyl PEGylated Fe3O4 nanoparticles. XRD and TEM analyses revealed the formation of single phase inverse spinel Fe3O4 nanoparticles of a size of about 10 nm. The successful growth of the polyaniline shell on the surface of carboxyl PEGylated magnetic nanoparticles (CPMN) is evident from FTIR spectra, DLS, TGA, zeta-potential and magnetic measurements. Both CPMN and PSMN show good colloidal stability, superparamagnetic behavior at room temperature and excellent heating efficacy under AMF. It has been observed that the heating efficacy of PSMN under AMF was slightly reduced as compared to that of CPMN. The enhanced toxicity of PSMN to cancer cells under AMF suggests their strong potential for magnetic hyperthermia. Furthermore, PSMN shows high loading affinity for an anticancer drug (doxorubicin), its sustained release and substantial internalization in tumor cells.
Asunto(s)
Compuestos de Anilina/farmacología , Nanopartículas de Magnetita , Compuestos de Anilina/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Calor , Hipertermia Inducida , Campos Magnéticos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Ratones , Microscopía Confocal , Microscopía Electrónica de Transmisión , Neoplasias/terapia , Difracción de Rayos XRESUMEN
We report the development of carboxyl decorated iron oxide nanoparticles (CIONs) by a facile soft-chemical approach for magnetic resonance imaging (MRI) and hyperthermia applications. These superparamagnetic CIONs (~10 nm) are resistant to protein adsorption under physiological medium and exhibit good colloidal stability, magnetization and cytocompatibility with cell lines. Analysis of the T2-weighted MRI scans of CIONs in water yields a transverse relaxivity (r2) value of 215 mM(-1) s(-1). The good colloidal stability and high r2 value make these CIONs as promising candidates for high-efficiency T2 contrast agent in MRI. Further, these biocompatible nanoparticles show excellent self-heating efficacy under external AC magnetic field (AMF). The infrared thermal imaging confirmed the localized heating of CIONs under AMF. Thus, these carboxyl decorated Fe3O4 nanoparticles can be used as a contrast agent in MRI as well as localized heat activated killing of cancer cells. Furthermore, the active functional groups (COOH) present on the surface of Fe3O4 nanoparticles can be accessible for routine conjugation of biomolecules/drugs through well-developed bioconjugation chemistry.
Asunto(s)
Medios de Contraste/química , Óxido Ferrosoférrico/química , Glicina/química , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Animales , Células Sanguíneas/citología , Células Sanguíneas/efectos de los fármacos , Línea Celular , Medios de Contraste/farmacología , Óxido Ferrosoférrico/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Colorantes Fluorescentes , Células HeLa , Hemólisis/efectos de los fármacos , Humanos , Hipertermia Inducida , Campos Magnéticos , Nanopartículas de Magnetita/ultraestructura , Ratones , Microscopía Electrónica de Transmisión , Rodaminas , Difracción de Rayos XRESUMEN
We demonstrate a single-step facile approach for the synthesis of glycine (amino acid) passivated Fe(3)O(4) magnetic nanoparticles (GMNPs) using soft chemical route. The surface passivation of Fe(3)O(4) nanoparticles with glycine molecules was evident from infrared spectroscopy, thermal and elemental analyses, and light scattering measurements. These nanoparticles show better colloidal stability, good magnetization, excellent self-heating capacity under external AC magnetic field and cytocompatibility with cell lines. Further, the active functional groups (-NH(2)) present on the surface of Fe(3)O(4) nanoparticles can be accessible for routine conjugation of biomolecules/biolabelling through well-developed bioconjugation chemistry. Specifically, a new colloidal glycine passivated biocompatible Fe(3)O(4) nanoparticles with excellent specific absorption rate (SAR) have been fabricated, which can be used as an effective heating source for hyperthermia treatment of cancer (thermal therapy).
Asunto(s)
Compuestos Férricos/química , Compuestos Férricos/uso terapéutico , Glicina/química , Glicina/uso terapéutico , Hipertermia Inducida , Nanopartículas/química , Nanopartículas/uso terapéutico , Animales , Línea Celular , Células HeLa , Humanos , Hipertermia Inducida/métodos , Ratones , Nanopartículas/ultraestructuraRESUMEN
The research on biomedical applications of nanoparticles has seen an upsurge in recent years due to their unique capabilities in treatment of ailments. Though there are ample reviews on the advances of nanoparticles right from their fabrication to applications, comparatively fewer reviews are available for the nanostructured materials particularly on oxides and hybrids. These materials possess unique physicochemical properties with an ability to get functionalized at molecular and cellular level for biochemical interactions. Keeping the enormosity of the nanostructures in mind, we intend to cover only the recent and most noteworthy developments in this area. We, particularly emphasize on iron oxide and its derivatives, zinc oxides, layered double hydroxides, silica and binary/ternary metal oxides and their applications in the area of therapeutics. This review also focuses on the designing of biodegradable and biocompatible nanocarriers and critical issues related to their therapeutic applications. Several representative examples discuss targeting strategies and stimuli responsive nanocarriers and their therapeutics.