Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel

Abstract

The resistance of cancer cells to chemotherapeutic drugs (MDR) is a major problem to be solved. A supramolecular DEAE-dextran-MMA copolymer (DDMC)/paclitaxel (PTX) complex was obtained by using PTX as the guest and DDMC as the host having 50-300 nm in diameter. The drug resistance of B16F10 melanoma cells to paclitaxel was observed, but there is no drug resistance of melanoma cells to the DDMC/PTX complex in vitro. The cell death rate was determined using Michaelis-Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size, 50 nm), and DDMC/PTX5 (particle size, 290 nm) groups were 120 h (T/C, 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed the twofold effectiveness of PTX alone (p < 0.036). Histochemical analysis indicated that the administration of DDMC/PTX complex decreased distant metastasis and increased the survival of mice. A mouse of DDMC/PTX4 group in vivo was almost curing after small dermatorrhagia owing to its anti-angiogenesis, and it will be the hemorrhagic necrotic symptom of tumor by the release of "tumor necrosis factor alpha (TNF-α)" cytokine. As the result, the medicinal action of the DDMC/PTX complex will suppress the tumor-associated action of M2 macrophages and will control the metastasis of cancer cells.

Developing a Novel Gene-Delivery Vector System Using the Recombinant Fusion Protein of Pseudomonas Exotoxin A and Hyperthermophilic Archaeal Histone HPhA

“…These systems have inherent limitations and disadvantages, regardless either viral or non-viral vectors [ 32 , 33 ]. Although gene transfers via receptors or mediated by DEAE-dextran may enhance the function of endocytosis, any successful application has not yet been reported [ 34 , 35 ]. A novel gene delivery method still needs to be developed.…”

Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

“…Macrophages promote cancer initiation and progression by releasing cytokines. Alteration of macrophage phenotype and function has a profound effect on inflammatory tumors, in close association with macrophage-induced lymphangiogenesis [ 136 , 137 , 138 ]. The macrophage recruitment to the tumor microenvironment may activate the transcriptional factors (STAT3, HIF-lα, AP-1 and NF-κB) in cancer cells, which further enhance the production of several inflammatory mediators, cytokines and enzymes to accelerate LN metastasis [ 13 , 139 ].…”

“…The anticancer efficacy of a supramolecular complex was reported to be used as an artificial enzyme against multi-drug-resistant cancer cells. Tumor actively-targeted theranostic nanoparticles have been developed for therapeutic and diagnostic applications [ 136 , 189 ]. In addition, despite small-molecule drugs, biologics, miRNA, RNA interference (RNAi) and vaccines are under active investigation, the cancer stem cell (CSCs) involved in tumor-induced lymphangiogenesis are now emerging as a plausible target for new drug discovery [ 190 , 191 ].…”