RESUMEN
Theranostic agents based on magnetic resonance imaging (MRI) and photothermal therapy (PTT) play an important role in tumor therapy. However, the available theranostic agents are facing great challenges such as biocompatibility, MRI contrast effect and photothermal conversion efficiency (η). In this work, mesoporous polydopamine nanoparticles (MPDAPs/Mn) were prepared on MRI and PTT combined theranostic nanoplatforms, of which the high loading manganese ions and specific surface areas enable good MRI contrast and excellent photothermal conversion efficiency, respectively. The MPDAPs/Mn have uniform morphology, good stability and biocompatibility. Meanwhile, in vitro and in vivo studies have confirmed their superior T1-weighted MRI effect and photothermal conversion efficiency. Furthermore, MPDAPs/Mn have excellent antitumor efficacy in HeLa tumor-bearing mice. Therefore, this developed MPDAPs/Mn theranostic nanoplatform could be a promising candidate for MRI-guided photothermal cancer therapy.
Asunto(s)
Manganeso , Nanopartículas , Animales , Humanos , Indoles , Iones , Imagen por Resonancia Magnética , Ratones , Fototerapia , Terapia Fototérmica , Polímeros , Nanomedicina TeranósticaRESUMEN
Novel "zwitterionic" gold nanorods (Au NRs) were constructed through a facile ligand exchange process between cetyltrimethylammonium bromide (CTAB)-Au NRs and the zwitterionic block polymer {poly(2-methacryloyloxyethyl phosohorylcholine)-b-poly(lipoic methacrylate) (pMPC-b-pLA)}. In vitro, they exhibited low dark cytotoxicity and a high therapeutic efficacy to cancer cells. Their blood circulation half-life in vivo (t1/2, â¼10 h) was 20-fold longer than that of CTAB-Au NRs (t1/2, <30 min). After intravenous administration, they accumulated in tumour sites via an enhanced permeability and retention (EPR) effect and enabled destruction of human xenograft tumours in mice after exposure of the tumour location to NIR laser irradiation at 808 nm. These studies showed that the "zwitterionic" Au NRs had low toxicity and high photothermal efficacy both in vitro and in vivo due to the suprahydrophilic, biocompatible zwitterionic polymer coating layer. They may have the potential to be a promising NIR PTT agent in the biomedical field.
Asunto(s)
Compuestos de Cetrimonio/uso terapéutico , Oro/uso terapéutico , Nanotubos , Neoplasias/terapia , Fosforilcolina/análogos & derivados , Ácidos Polimetacrílicos/uso terapéutico , Animales , Línea Celular Tumoral , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/farmacocinética , Compuestos de Cetrimonio/farmacología , Oro/química , Oro/farmacocinética , Oro/farmacología , Humanos , Hipertermia Inducida/métodos , Células MCF-7 , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanotubos/análisis , Nanotubos/química , Nanotubos/ultraestructura , Neoplasias/patología , Fosforilcolina/química , Fosforilcolina/farmacocinética , Fosforilcolina/farmacología , Fosforilcolina/uso terapéutico , Fototerapia/métodos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/farmacologíaRESUMEN
Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.