RESUMO
Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.
Assuntos
Ferroptose , Fototerapia , Nanomedicina Teranóstica , Humanos , Ferroptose/efeitos dos fármacos , Fototerapia/métodos , Animais , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Ferro/química , Polietilenoglicóis/química , Camundongos , Fotoquimioterapia/métodosRESUMO
Flexible electrode array, a new-generation neural microelectrode, is a crucial tool for information exchange between living tissues and external electronics. Till date, advances in flexible neural microelectrodes are limited because of their high impedance and poor mechanical consistency at tissue interfaces. Herein, a highly sensitive and omnidirectionally stretchable polymeric electrode array (PEA) is introduced. Micropyramid-nanowire composite structures are constructed to increase the effective surface area of PEA, achieving an exponential reduction in impedance compared with gold (Au) and flat polypyrrole electrodes. Moreover, for the first time, a suspended umbrella structure to enable PEA with omnidirectional stretchability of up to ≈20% is designed. The PEA can withstand 1000 cycles of mechanical loads without decrease in performance. As a proof of concept, PEA is conformally attached to a rat heart and tibialis anterior muscle, and electrophysiological signals (electrocardiogram and electromyogram) of the rat are successfully recorded. This strategy provides a new perspective toward highly sensitive and omnidirectionally stretchable PEA that can facilitate the practical application of neural electrodes.
Assuntos
Polímeros , Pirróis , Ratos , Animais , Microeletrodos , Músculo Esquelético , Impedância ElétricaRESUMO
Reducing the swelling of tissue-adhesive hydrogels is crucial for maintaining stable tissue adhesion and inhibiting tissue inflammation. However, reported strategies for reducing swelling always result in a simultaneous decrease in the tissue adhesive strength of the hydrogel. Furthermore, once the covalent bonds break in the currently reported hydrogels, they cannot be rebuilt, and the hydrogel loses its tissue adhesive ability. In this work, a nonswelling hydrogel (named as "PAACP") possessing regenerable high tissue adhesion is synthesized by copolymerizing and crosslinking poly(vinyl butyral) with acrylic acid, gelatin, and chitosan-grafted N-acetyl-l-cysteine. The tissue adhesive strength of the obtained PAACP reaches 211.4 kPa, which is approximately ten times higher than that of the reported nonswelling hydrogels, and the hydrogel can be reused for multiple cycles. The as-prepared hydrogel shows great potential in soft bioelectronics, as muscle fatigue is successfully monitored via the electrode array and strain sensor integrated on PAACP substrates. The success of these bioelectronics offers potential applicability in the long-term diagnosis of muscle-related health conditions and prosthetic manipulations.
Assuntos
Quitosana , Adesivos Teciduais , Adesivos Teciduais/química , Hidrogéis/química , Quitosana/química , Gelatina/químicaRESUMO
There is great potential for photodynamic therapy (PDT)-enhanced photothermal therapy (PTT) to be used for tumor therapy, especially for the single material-mediated process that could greatly simplify the experimental arrangements. This study presents a new cancer phototherapeutic agent consisting of low-work-function lanthanum hexaboride particles, which are excellent light absorbers in the near-infrared (NIR) region. The photothermal effect and reactive oxygen species production were realized by LaB6 under NIR light irradiation. Theoretical calculations based on density functional theory confirmed that the strong NIR light absorption by LaB6 was attributed to the local plasmonic resonance effect and the excellent photodynamic effect derived from the low work function. In vivo treatment of HepG2 tumor-bearing mice revealed that LaB6-mediated phototherapy resulted in excellent tumor inhibitory effects, and no adverse effects on mice were observed. These results indicate that LaB6 is a promising phototherapeutic agent for cancer synergetic phototherapy.