RESUMEN
Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy.
Asunto(s)
Hipertermia Inducida , Nanopartículas de Magnetita , Péptidos , Hipertermia Inducida/métodos , Humanos , Nanopartículas de Magnetita/química , Péptidos/química , Péptidos/farmacología , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/patología , Campos MagnéticosRESUMEN
4-Methyl-5-pentylbenzene-1,3-diol (MPBD), a product of the polyketide synthase SteelyA, is a signaling molecule that regulates Dictyostelium discoideum development. During early development, MPBD controls chemotactic cell aggregation by regulating the expression of genes in the cAMP signaling pathway; however, during culmination at late development, it induces spore maturation. In the present study, we analyzed the effects of MPBD, its derivatives, and a putative MPBD-derived metabolite on developmental defects in the MPBD-less stlA null mutant. Using structure-activity relationship studies, it was observed that in MPBD, the functional groups that were essential for induction of spore maturation were different from those essential for induction of cell aggregation. Dictyoquinone, a putative MPBD metabolite rescued the aggregation defect in stlA null mutant in early development, but not the spore maturation defect at the later stage. Our data suggest that MPBD regulates chemotactic cell aggregation and spore maturation via different mechanisms.
Asunto(s)
Quimiotaxis/fisiología , Dictyostelium/fisiología , Resorcinoles/metabolismo , Esporas Protozoarias/crecimiento & desarrollo , Benzoquinonas/farmacología , Quimiotaxis/efectos de los fármacos , Dictyostelium/genética , Dictyostelium/crecimiento & desarrollo , Dictyostelium/metabolismo , Expresión Génica/efectos de los fármacos , Mutación , Sintasas Poliquetidas/genética , Proteínas Protozoarias/genética , Resorcinoles/química , Resorcinoles/farmacología , Esporas Protozoarias/genética , Esporas Protozoarias/metabolismo , Esporas Protozoarias/fisiología , Relación Estructura-ActividadRESUMEN
4-Methyl-5-pentylbenzene-1,3-diol (MPBD) is a secondary metabolite of SteelyA polyketide synthase, which controls cell aggregation and spore maturation of Dictyostelium discoideum. In this study, chemical synthesis of MPBD and its derivatives was achieved. Structure-activity relationship (SAR) studies for antimicrobial activities against Escherichia coli and Bacillus subtilis were also conducted.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Dictyostelium/química , Escherichia coli/efectos de los fármacos , Resorcinoles/síntesis química , Resorcinoles/farmacología , Antibacterianos/síntesis química , Dictyostelium/metabolismo , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resorcinoles/química , Relación Estructura-ActividadRESUMEN
Combination therapy for cancer is expected for the synergetic effect of different treatments, and the development of promising carrier materials is demanded for new therapeutics. In this study, nanocomposites including functional nanoparticles (NPs) such as samarium oxide NP for radiotherapy and gadolinium oxide NP as a magnetic resonance imaging agent were synthesized and chemically combined with iron oxide NP-embedded or carbon dot-coating iron oxide NP-embedded carbon nanohorn carriers, where iron oxide NP is a hyperthermia reagent and carbon dot exerts effects on photodynamic/photothermal treatments. These nanocomposites exerted potential for delivery of anticancer drugs (doxorubicin, gemcitabine, and camptothecin) even after being coated with poly(ethylene glycol). The co-delivery of these anticancer drugs played better drug-release efficacy than the independent drug delivery, and the thermal and photothermal procedures enlarged the drug release. Thus, the prepared nanocomposites can be expected as materials to develop advanced medication for combination treatment.