RESUMEN
Immunotherapy has emerged as a promising new approach for cancer treatment. However, clinically available drugs have been limited until recently, and the antitumor efficacy of most cancer immunotherapies still needs to be improved. Herein, we develop diselenide-pemetrexed assemblies that combine natural killer (NK) cell-based cancer immunotherapy with radiotherapy and chemotherapy in a single system. The assemblies are prepared by co-assembly between pemetrexed and cytosine-containing diselenide through hydrogen bonds. Under γ-radiation, the hydrogen bonds are cleaved, resulting in the release of pemetrexed. At the same time, diselenide can be oxidized to seleninic acid, which suppresses the expression of human leukocyte antigen E (HLA-E) in cancer cells, thus activating the immune response of NK cells. In this way, cancer immunotherapy is combined with radiotherapy and chemotherapy, providing a new strategy for cancer treatment.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/terapia , Compuestos de Organoselenio/farmacología , Pemetrexed/farmacología , Antineoplásicos/química , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Inmunoterapia , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Estructura Molecular , Compuestos de Organoselenio/química , Pemetrexed/químicaRESUMEN
Gold-chalcogen interactions are ubiquitous in gold biological and medicinal systems. Understanding the nature of these interactions can provide the basis for regulating their structures and functionalities, and a reasonable way to interpret the differences in various properties. However, the relative strength of gold-chalcogen bonds remains controversial, and the conclusions of many related works are inconsistent. Thus, in this work, we successfully quantified the relative strength of Au-X (X=S, Se, and Te from chalcogenide-containing A-B-A type block copolymers) interactions at the single-molecule level through single-molecule force spectroscopy (SMFS) from a kinetic point of view and quantum chemical studies from a thermodynamic point of view. Both sets of results suggested that the strength of the Au-X bonds decreases as Au-Te>Au-Se>Au-S. Our findings unveiled the relative strength and nature of gold-chalcogen interactions, which may help expand their application in electronics, catalysis, medicine and many other fields.
RESUMEN
It is urgently desired that self-assembly methods can be used to develop smart nanomedicines with adjustable anticancer activity and concise structure. Herein, we design carrier-free small molecule assemblies of platinum coordinated selenomethionine, which exhibit adjustable anticancer activity regulated by their self-assembly behaviors. The small molecule assemblies are prepared by coordination of selenomethionine esters with cisplatin. Their self-assembly behaviors can be tuned by esterification between selenomethionine and alcohols with different alkyl lengths, which results in adjustable anticancer activities. The coordination assemblies exhibit high anticancer activity as well as low side effects. Mechanistic studies indicate that they can consume glutathione (GSH) and therefore induce high level of reactive oxygen species (ROS) in cancer cells, which further lead to cell apoptosis. Our findings provide new strategies and insights in developing small molecule assemblies for cancer treatment.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Complejos de Coordinación/farmacología , Neoplasias/tratamiento farmacológico , Selenometionina/química , Células A549 , Animales , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Cisplatino/química , Complejos de Coordinación/química , Femenino , Glutatión/metabolismo , Células Hep G2 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/patología , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Selenium has attracted increasing interest in recent decades because of the function of regulating the redox balance in the human body. However, biomedical studies of selenium are still limited. Gold nanoparticles (AuNPs), typically prepared by a first reduction step followed by a second stabilization step, are widely applied in biomedical studies. However, their own anticancer activity is less studied. Here, we report 2 nm AuNPs with significant anticancer activity (IC50 = 20 µM) that is stabilized by a selenium-containing amphiphile EGSe-tMe. The AuNPs are prepared by simply mixing chloroauric acid (HAuCl4) with EGSe-tMe, which acts as both a reducing agent and a stabilizer. In contrast to AuNPs prepared by EGSe-tMe, EGSe-tMe alone and typically prepared AuNPs show little anticancer activity even at concentrations up to 250 µM. Mechanistic studies suggest that selenium in cooperation with AuNPs can induce high concentrations of reactive oxygen species (ROS) in cancer cells, leading to cellular apoptosis.
Asunto(s)
Nanopartículas del Metal , Apoptosis , Oro , Humanos , Neoplasias , Especies Reactivas de Oxígeno , SelenioRESUMEN
Two-dimensional (2D) nanoheterostructure (2D NHS) with nanoparticles grown on 2D nanomaterial substrates could potentially enable many novel functionalities. Controlled site-selective growth of nanoparticles on either the lateral or the basal directions of 2D nanomaterial substrates is desirable but extremely challenging. Herein, we demonstrate the rational control of lateral- and basal-selective attachment of CdS nanoparticles onto 2D Bi2Se3 nanosheets through solution phase reactions. The combination of experimental and theoretical efforts elucidate that site-relevant interfacial bonding and kinetic control of molecular precursors play vital roles for site selectivity. Furthermore, the electronic structures revealed from density functional theory calculations explain the superior performance of the lateral 2D NHSs compared to their basal counterpart in prototype photoelectrochemical cells. The present study will inspire the construction of other site-selective 2D NHSs with well-defined structure and unique properties.