RESUMEN
Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O2-â¢) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.
Asunto(s)
Celecoxib , Lutecio , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Animales , Humanos , Porfirinas/química , Porfirinas/farmacología , Ratones , Lutecio/química , Celecoxib/química , Celecoxib/farmacología , Inmunoterapia , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , FemeninoRESUMEN
Microwave (MW) hyperthermia has been widely studied in tumor therapy, while the lack of specificity, and the potential toxicity induced by instability or difficulty in degradation of existed MW thermal sensitizers still limits the application. Herein, a new biocompatible Poly(lactic-co-glycolic acid) (PLGA)-based nanosensitizer of Dtxl-Gd@PLGA-PEG-TPP (DGPPT) with capacities of magnetic resonance (MR) imaging and mitochondrial targeting for MW hyperthermia combined with chemotherapy was constructed via a double emulsion solvent evaporation method. The modified TPP significantly enhanced the specificity of sensitizer for targeting mitochondria, a heat-sensitive energy supply plant in cells. Thus the MW thermal damage induced by the loaded Gd in PLGA nanospheres was also strengthened. Together, the system could also achieve MR imaging due to the existence of Gd. In addition, the encapsulated Dtxl performed the chemotherapy of inhibiting mitochondrial function for assisting with MW hyperthermia. In vivo experiments demonstrated that PLGA had high biocompatibility that no obvious damage occurred even the dose was up to 200 mg/kg. Meanwhile, DGPPT+MW representing the combination of mitochondrial targeting and MW hyperthermia-chemotherapy has also been proved to shrink tumor size effectively. This study provides a new direction for building biosafe and multifunctional MW sensitizer with active targeting ability to impede tumor growth.
Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Ácido Láctico , Imagen por Resonancia Magnética/métodos , Microondas , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Polietilenglicoles , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
Since Earth's biochemistry is carbon-based and water-borne, the main strategies for searching for life elsewhere are "follow the carbon" and "follow the water." Recently, however, there is a growing focus on the prospect that putative exotic life on other planets could rely on unearthly biochemistries. Here, we hypothesize a novel oxygen-free organic chemistry for supporting potential exotic biosystems, which is named CHN biochemistry. This oxygen-free CHN biochemistry starts from simple oxygen-free species (including hydrocarbons, hydrogen cyanide, and nitriles) and produces a range of functional macromolecules that may function in similar ways to terran macromolecules, such as sugars (cyanosugars), acids (cyanoacids), amino acids (amino cyanoacids), and nucleobases (cyanonucleobases). These CHN macromolecules could further interact with each other to generate higher "cyanoester" and "cyanoprotein" systems. In addition, theoretical calculations indicate that the energy changes of some reactions are consistent with their counterparts in Earth's biochemistry. The CHN biochemistry-based life would be applicable in habitats with a low bioavailability of oxygen, such as the alkane lakes of Titan and non-aquatic liquids on extrasolar bodies. Key Words: Oxygen-free biochemistry-Titan-Hydrocarbons-Hydrogen cyanide-Nitriles. Astrobiology 17, 1173-1181.
Asunto(s)
Atmósfera/química , Medio Ambiente Extraterrestre/química , Hidrocarburos/química , Origen de la Vida , Saturno , Carbono/química , Planeta Tierra , Cianuro de Hidrógeno/química , Nitrilos/química , Oxígeno/químicaRESUMEN
Gold nanorods (AuNRs) can be successfully co-assembled with Ag nanowires (AgNWs) to form a kind of AuNR-AgNW nanocomposite by electrostatic attraction, in which the AuNRs are arranged along the long axial direction of the AgNWs with a preferential string-like alignment. The assembled AuNR-AgNW nanocomposites are then further embedded within polyvinyl alcohol (PVA) nanofibers by electrospinning, by which both AuNRs and AgNWs can be stabilized and arranged along the axis of polymer nanofibers. When the polymer nanofibers are aligned by collecting on a copper mesh with a woven structure, the AuNR-AgNW nanocomposites assembled within the electrospun nanofibers are also arranged. The influences of the AuNR-AgNW assemblies with different amounts of AuNRs attached on AgNWs on the optical properties and surface enhanced Raman scattering (SERS) enhancement have been investigated. The resulting AuNR-AgNW/PVA electrospun mats show red-shifted and broader absorption bands and higher SERS performances compared with the normal casting films with randomly dispersed AuNRs and AgNWs, or electrospun mats with monometallic components, due to the order alignment of AuNR-AgNW nanocomposites on a large scale.
Asunto(s)
Oro/química , Nanofibras/química , Nanotubos/química , Nanocables/química , Alcohol Polivinílico/química , Plata/química , Nanofibras/ultraestructura , Nanotubos/ultraestructura , Polímeros/química , Espectrometría RamanRESUMEN
Under control: Controlled assemblies of gold nanorods in a poly(vinyl alcohol) (PVA) nanofiber matrix with tunable optical properties can be achieved by using electrospinning. The resultant assemblies can be used as substrates for surface-enhanced Raman spectroscopy (SERS). This work provides a facile way to control alignment of anisotropic nanostructures in a polymer nanofiber matrix and generates new assemblies with interesting properties.