RESUMEN
Mucin-1 (MUC1) is a highly relevant antigen for cancer vaccination due to its overexpression and hypo-glycosylation in a high percentage of carcinomas. To enhance the immune response to MUC1, our group has developed C3-liposomes that encapsulate the MUC1 antigen along with immunostimulatory compounds for direct delivery to antigen-presenting cells (APCs). C3-liposomes bind complement C3, which interacts with C3-receptors on APCs, resulting in liposomal uptake and the delivery of tumor antigens to APCs in a manner that mimics pathogenic uptake. In this study, MUC1 and Toll-like receptor (TLR) agonists were encapsulated in C3-liposomes to provoke an immune response in transgenic mice tolerant to MUC1. The immune response to the C3-bound MUC1 liposomal vaccine was assessed by ELISA, ELISpot, and flow cytometry. Co-administering TLR 7/8 agonists with MUC1 encapsulated in C3-liposomes resulted in a significant antibody response compared to non-encapsulated MUC1. This antibody response was significantly higher in females than in males. The co-encapsulation of three TLR agonists with MUC1 in C3-liposomes significantly increased antibody responses and eliminated sex-based differences. Furthermore, this immunization strategy resulted in a significantly increased T cell-response compared to other treatment groups. In conclusion, the co-delivery of MUC1 and TLR agonists via C3-liposomes greatly enhances the immune response to MUC1, highlighting its potential for antigen-specific cancer immunotherapy.
RESUMEN
The anticancer properties of well-defined molecules serve to bolster the field of metals in medicine. Such compounds, particularly those of platinum and their closely related structural analogs, continue to be potentially highly interesting to researchers and clinicians alike. The four octahedral organoplatinum(IV) compounds [Pt(CH3)2X2{bipy-R 2 }] (X = Br, I; bipy-R 2 = 2,2'-bipyridine, 2,2'-bipyridine-4,4'-dicarboxylic acid) have been isolated and structurally characterized by single-crystal X-ray diffraction. Nuclear magnetic resonance and infrared spectroscopic data are also tabulated as useful reference values. The anticancer potential of each compound was assessed via in vitro MTT assays, using human breast cancer cells (cell line ZR-75-1). EC50 values were determined as 11.5 µM for Pt(CH3)2Br2{bipy}; 3020 µM, for Pt(CH3)2Br2{bipy-(CO 2 H) 2 }; 6.1 µM, for Pt(CH3)2I2{bipy}; and 86.0 µM, for Pt(CH3)2I2{bipy-(CO 2 H) 2 }; for comparison, the EC50 value for cisplatin against the ZR-75-1 cells was 16.4 µM. The most cytotoxic of the four compounds Pt(CH3)2I2{bipy} undergoes reaction with glutathione in a THF/water mixture at 68°C very slowly.
RESUMEN
Herein, we report the synthesis and characterization of homochiral macrocycles, in which molecular rigidity, combined with the presence of multiple functional groups, allow for the assembly of helical nanostructures. 1,1'-bi-2-naphthol (Binol) units are used as robust chirality inducers, and pyridyl units embedded within the molecular frameworks allow the assembly, upon coordination with Pd(II) metal ions, of the macrocyclic building blocks. CD and NMR spectroscopies show the formation of ordered 1D assembly in solution. AFM studies indicate that the molecular systems are capable of forming nanoscale structures. The effective transfer of chiral information results in helical nanofibers, with lengths ranging from a few hundreds of nanometers to some micrometers. AFM line profiles reveal a helical longitudinal period of about 50â nm and a transverse width of 25 to 45â nm after deconvolution.
RESUMEN
In the tumor microenvironment, cytokines, growth factors, and oncogenes mediate constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in both cancer cells and infiltrating immune cells. STAT3 activation in cancer cells drives tumorigenic changes that allow for increased survival, proliferation, and resistance to apoptosis. The modulation of immune cells is more complicated and conflicting. STAT3 signaling drives the myeloid cell phenotype towards an immune suppressive state, which mediates T cell inhibition. On the other hand, STAT3 signaling in T cells leads to proliferation and T cell activity required for an anti-tumor response. Targeted delivery of STAT3 inhibitors to cancer cells and myeloid cells could therefore improve therapeutic outcomes. Many compounds that inhibit the STAT3 pathways for cancer treatment include peptide drugs, small molecule inhibitors, and natural compounds. However, natural compounds that inhibit STAT3 are often hydrophobic, which reduces their bioavailability and leads to unfavorable pharmacokinetics. This review focuses specifically on liposome-encapsulated natural STAT3 inhibitors and their ability to target cancer cells and myeloid cells to reduce tumor growth and decrease STAT3-mediated immune suppression. Many of these liposome formulations have led to profound tumor reduction and examples of combination formulations have been shown to eliminate tumors through immune modulation.