RESUMO
Magnetic hyperthermia (MH) has been studied for almost seventy-five years, but its efficacy in clinical applications is still fiercely contested. Despite this, few magnetic nanosystems are approved for clinical usage due to their strong affinity as drug carriers. The most important condition for hyperthermia applications for successful cancer therapy is magnetic nanoparticles with a controlled heating pattern (42-46 °C) for a prolonged timeframe. In the current study, cobalt-zinc nanoferrites (MNPs) having a Curie temperature of 46 â with a tunable heating profile was loaded with Doxorubicin (DOX) through a surface conjugation technique (DOX-Cs-MNPs), and characterized by using multiple techniques. The magnetic hyterises (M-H) curves revealed the occurrence of superparamagnetism in the MNPs with extremely low coercivity; further, the DOX-loaded nanoparticles exhibited enhanced saturation magnetization. More importantly, the MNPs showed that they could maintain a therapeutic temperature for an indefinite amount of time. High drug loading affinity (86 %) was observed on MNPs with pH and temperature-controlled release. Under in vitro conditions, the biocompatible DOX-Cs-MNPs caused substantial apoptosis in MCF-7 cells (72 %) with overall cell death of < 95 %. The distinctive MNPs thus have the potential to be used in clinical applications.
Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias , Humanos , Zinco , Doxorrubicina/farmacologia , Doxorrubicina/química , Cobalto/farmacologia , Cobalto/química , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológicoRESUMO
Porphyrin is known to enable the photodynamic effect during cancer drug delivery and molecular imaging. However, its hydrophobicity and tendency to aggregate in an aqueous medium create a significant hurdle for its use as an anticancer drug. Loading porphyrin onto biocompatible delivery vehicles can enhance its efficacy. This can be achieved by using gas-filled microbubbles that can be administered intravenously. This study aimed at developing near-infrared (NIR)-active porphyrin-loaded lipid microbubbles with anticancer activity enhanced by sonodynamic and photodynamic effects. The porphyrin-loaded microbubbles were studied for their cell toxicity, cellular uptake of porphyrin, and effect on cellular three-dimensional (3D) invasion of breast cancer cells (MDA-MB-231) in cellulo. Toxicity studies in zebrafish larvae (Danio rerio) in the presence and absence of photodynamic and sonodynamic therapy were also conducted. The results suggest that with a higher concentration of porphyrin loaded on microbubbles, the porphyrin-loaded microbubbles display a higher therapeutic effect facilitated by photodynamic and sonodynamic therapy, which results in enhanced cellular uptake and cellular toxicity. A lower concentration of loaded porphyrin microbubbles exhibits high cellular viability and good fluorescence intensity in the NIR region, which can be exploited for bioimaging applications.
RESUMO
Carbon-based nanostructures with nanometer dimensions have been identified as potential photoluminescence probes for bioimaging due to their biocompatibility, tunable bandgap, and resistance to photobleaching. However, the influence of structural features of carbon quantum dots (CQDs) and graphene quantum dots (GQDs) in bioimaging has not been explored previously. In the present investigation, we elucidated the mechanism of higher PL in GQDs as compared to CQDs as a function of their structural features. TEM and AFM studies revealed that CQDs were spherical (size ~5 nm), while GQDs showed zigzag edges (size ~3 nm). Further, XRD and NMR studies confirmed that CQDs and GQDs show amorphous and crystalline structures with greater sp2 clusters, respectively. While both the QDs demonstrated multicolor fluorescence against variable excitations with similar lifetime, GQDs showed 7-fold higher QY than CQDs. Bioimaging studies in 2D cell culture, 3D tumoroids, and in vivo suggested a greater intensity of fluorescence in GQDs than CQDs. Additionally, rapid cell internalization was observed in GQDs owing to their positive surface potential by heterogeneous atomic (N and S) doping. Moreover, both CQDs and GQDs have demonstrated better time dependent stability for fluorescence properties. Taken together, the proposed mechanism elucidates the greater PL intensity in GQDs due to quantum confinement effect, crystallinity, and surface edge effects and is a better candidate for bioimaging amongst the carbon family.