RESUMEN
To enhance the therapeutic efficiency and reduce side effects from drug delivery and chemotherapy, image-guided nanoscale systems have attracted tremendous attention in recent decades. In this study, we developed a novel method to fabricate a colchicine/gadolinium-loaded tubulin self-assembly nanocarrier (Col-Gd@Tub NC) for the image-guided chemotherapy of glioma. The Col-Gd@Tub NCs were spontaneously formed via tubulin self-assembly and were subsequently functionalized by colchicine and gadolinium elements. These resultant Col-Gd@Tub NCs with a diameter of 45 nm exhibited uniform particle size distribution and favorable stability without any leakage of gadolinium in water. Meanwhile, the introduction of gadolinium endowed Col-Gd@Tub NCs with high T 1-weighted MRI performance in vitro. After tail vein injection, Col-Gd@Tub NCs exhibited excellent MRI contrast capability and relatively long circulation time (â¼12 h) and were finally cleared out from the bladder. More significantly, the binding colchicine still exerted an anti-tumor effect after the Col-Gd@Tub NCs were taken up by the tumor cells. These results show that the Col-Gd@Tub NCs may be served as a versatile nanoscale platform for the integration of biomedical imaging probes and therapeutic molecules for tumor therapy.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Colchicina/administración & dosificación , Gadolinio/química , Glioma/tratamiento farmacológico , Tubulina (Proteína)/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias Encefálicas/diagnóstico por imagen , Línea Celular Tumoral , Colchicina/química , Colchicina/farmacología , Dispersión Dinámica de Luz , Femenino , Glioma/diagnóstico por imagen , Células HEK293 , Humanos , Imagen por Resonancia Magnética , Nanopartículas del Metal , Ratones , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Pancreatic cancer is an aggressive and metastatic tumor that lacks effective early detection and treatment methods. There is an urgent need to further understand its underlying molecular mechanisms and identify new biomarkers for early detection. Zinc, a critical trace element and catalytic cofactor, is tightly regulated within cells. ZIP4, a zinc transporter protein significantly overexpressed in human pancreatic cancer, appears to play a pivotal role in tumor development by modulating intracellular zinc concentration. This review highlights the role of ZIP4 in tumorigenesis, including its impact on pancreatic cancer growth, proliferation, migration, and drug resistance. ZIP4 exerts its effects by regulating zinc dependent transcriptional factors like CREB, STAT3, and ZEB1, resulting in upregulation of Cyclin D1, TP53INP1, ITGA3, CD44, ENT1 proteins, and miR-373. Moreover, ZIP4 mediates the miR373-PHLPP2-AKT signaling axis, which increases TGF-ß expression. Coupled with CREB-activated macrophage catabolism-related genes SDC1 and DNM2, ZIP4 promotes cancer cachexia and supports amino acids to tumor cells under metabolic stress. Furthermore, ZIP4 facilitates bone resorption by osteoclasts via the RANKL-activated NF-κB pathway. A deeper understanding of these mechanisms may unveil potential targets for early diagnosis, prognosis assessment, and dietary recommendations for pancreatic cancer. These findings hold clinical significance not only for pancreatic cancer but also for other malignancies exhibiting heightened ZIP4 expression.