RESUMO
Efforts are made to perform an early and accurate detection of hepatocellular carcinoma (HCC) by simultaneous exploiting multiple clinically non-invasive imaging modalities. Original nanostructures derived from the combination of different inorganic domains can be used as efficient contrast agents in multimodal imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) and Au nanoparticles (NPs) possess well-established contrasting features in magnetic resonance imaging (MRI) and X-ray computed tomography (CT), respectively. HCC can be targeted by using specific carbohydrates able to recognize asialoglycoprotein receptor 1 (ASGPR1) overexpressed in hepatocytes. Here, two different thiocarbohydrate ligands were purposely designed and alternatively conjugated to the surface of Au-speckled silica-coated SPIONs NPs, to achieve two original nanostructures that could be potentially used for dual mode targeted imaging of HCC. The results indicated that the two thiocarbohydrate decorated nanostructures possess convenient plasmonic/superparamagnetic properties, well-controlled size and morphology and good selectivity for targeting ASGPR1 receptor.
Assuntos
Receptor de Asialoglicoproteína/metabolismo , Carboidratos/química , Carcinoma Hepatocelular/diagnóstico por imagem , Ouro , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanopartículas Metálicas/química , Dióxido de Silício , Compostos de Sulfidrila/química , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Although significant improvements in cancer treatment have led to a longer survival period, the death rate of patients with solid tumours has not changed during the last decades. Most researchers are currently concentrating on defining the mechanisms of the different resistance pathways activated by tumour cells; meanwhile, the role of limited drug distribution within tumours has been neglected. The application of nanotechnology in medicine offers unexplored opportunities for realizing a new generation of anticancer therapies that can overcome the physical hindrances that characterize solid tumours. Indeed, surface-engineered nanoparticles (NPs) (both organic and inorganic) have been used as powerful tools in cancer therapy. Particularly, Au NPs have been utilized to develop a new drug-free treatment, photo-thermal therapy (PTT), due to their stimuli-responsive properties. PTT combined with immunotherapy represents a major breakthrough in the fight against malignant solid tumours. In this review, we provide a complete overview of the synergistic approaches based on PTT and immunotherapy, considering the selection, design, and functionalization of the NPs and their thermo-optical properties, moving to in vivo studies and finally to clinical trial applications in patients suffering from solid tumours.
Assuntos
Imunoterapia , Nanopartículas/química , Neoplasias/terapia , Humanos , Tamanho da Partícula , Terapia Fototérmica , Propriedades de SuperfícieRESUMO
The low photostability of conventional organic dyes and the toxicity of cadmium-based luminescent quantum dots have prompted the development of novel probes for in vitro and in vivo labelling. Here, a new fluorescent lanthanide probe based on silica nanoparticles is fabricated and investigated for optically traceable in vitro translocator protein (TSPO) targeting. The targeting and detection of TSPO receptor, overexpressed in several pathological states, including neurodegenerative diseases and cancers, may provide valuable information for the early diagnosis and therapy of human disorders. Green fluorescent terbium(III)-calix[4]arene derivative complexes are encapsulated within silica nanoparticles and surface functionalized amine groups are conjugated with selective TSPO ligands based on a 2-phenylimidazo[1,2-a]pyridine acetamide structure containing derivatizable carboxylic groups. The photophysical properties of the terbium complex, promising for biological labelling, are demonstrated to be successfully conveyed to the realized nanoarchitectures. In addition, the high degree of biocompatibility, assessed by cell viability assay and the selectivity towards TSPO mitochondrial membrane receptors, proven by subcellular fractional studies, highlight targeting potential of this nanostructure for in vitro labelling of mitochondria.
Assuntos
Corantes Fluorescentes/química , Nanopartículas/química , Dióxido de Silício/química , Térbio/química , Calixarenos/química , Linhagem Celular Tumoral , Corantes Fluorescentes/farmacologia , Humanos , Ligantes , Fenóis/química , Ligação Proteica , Receptores de GABA/efeitos dos fármacos , Receptores de GABA/metabolismoRESUMO
We report the synthesis of various iron oxide nanocontainers and Pt-iron oxide nanoparticles based on a cast-mold approach, starting from nanoparticles having a metal core (either Au or AuPt) and an iron oxide shell. Upon annealing, the particles evolve to asymmetric core-shells and then to heterodimers. If iodine is used to leach Au out of these structures, asymmetric core-shells evolve into "nanocontainers", that is, iron oxide nanoparticles enclosing a cavity accessible through nanometer-sized pores, while heterodimers evolve into particles with a concave region. When starting from a metal domain made of AuPt, selective leaching of the Au atoms yields the same iron oxide nanoparticle morphologies but now encasing Pt domains (in their concave region or in their cavity). We found that the concave nanoparticles are capable of destabilizing Au nanocrystals of sizes matching that of the concave region. In addition, for the nanocontainers, we propose two different applications: (i) we demonstrate loading of the cavity region of the nanocontainers with the antitumoral drug cis-platin; and (ii) we show that nanocontainers encasing Pt domains can act as recoverable photocatalysts for the reduction of a model dye.