Suppression of Melanoma Growth and Metastasis by DNA Vaccination Using an Ultrasound-Responsive and Mannose-Modified Gene Carrier

Abstract

DNA vaccination has attracted much attention as a promising therapy for the prevention of metastasis and relapse of malignant tumors, especially highly metastatic tumors such as melanoma. However, it is difficult to achieve a potent cancer vaccine effect by DNA vaccination, since the number of dendritic cells, which are the major targeted cells of DNA vaccination, is very few. Here, we developed a DNA vaccination for metastatic and relapsed melanoma by ultrasound (US)-responsive and antigen presenting cell (APC)-selective gene carriers reported previously, named Man-PEG₂₀₀₀ bubble lipoplexes. Following immunization using US exposure and Man-PEG(2000) bubble lipoplexes constructed with pUb-M, which expresses ubiquitylated melanoma-specific antigens (gp100 and TRP-2), the secretion of Th1 cytokines (IFN-γ and TNF-α) and the activities of cytotoxic T lymphocytes (CTLs) were specifically enhanced in the presence of B16BL6 melanoma antigens. Moreover, we succeeded in obtaining potent and sustained DNA vaccine effects against solid and metastatic tumor derived from B16BL6 melanoma specifically. The findings obtained from this study suggest that the gene transfection method using Man-PEG₂₀₀₀ bubble lipoplexes and US exposure could be suitable for DNA vaccination aimed at the prevention of metastatic and relapsed cancer.

Tunable release of silver nanoparticles from temperature-responsive polymer blends

“…For these reasons incorporation of silver into smart matrices, able to sense external stimuli becomes one of the major challenge in the development of antimicrobial materials. Presently, temperature [7], pH [8], light [9], ultrasound [10], and magnetic field [11] are most common stimuli, which have been applied to trigger antimicrobial response of doped materials. Temperature sensitivity is commonly realized through special polymers, which undergo temperature-dependent phase transition.…”

Glycosylation-mediated targeting of carriers

“…The bubble liposomes had a small size (about 446 nm) compared with conventional microbubble formulation [212]. We developed mannosylated bubble liposome/pDNA complexes (mannosylated bubble lipoplexes) for efficient cell-selective gene transfection with ultrasound exposure [214][215][216][217]. This system could be used for delivery of oligonucleotides such as siRNA or NF-κB decoy delivery into liver NPC [218] or tumor-associated macrophages [219].…”

Combination of Nanoparticles with Physical Stimuli toward Cancer Therapy

“…21) DNA vaccination by the mannosylated PEGylated bubble lipoplex with ultrasound exposure suppressed melanoma growth and metastasis in vivo. 22) 2.3 Hyperthermia Tumors are generally sensitive to hyperthermia.…”