Macrophage-modification technique for treating metastatic solid tumors

Abstract

Systems and methods are provided that can keep adoptively transferred macrophages in solid tumors in the tumoricidal MI phenotype. Microparticles containing poly(N-isopropylacrylamide) (PNIPAM) and a multilayered structure made of deoxyribonucleic acid (DNA) and a polycation (PC) can be produced by depositing a multilayer of DNA and a PC and a layer of PNIPAM on a stamp bearing micropillars, followed by printing the disk-shaped structures on a substrate. The DNA/PC multilayer can be delivered into the cytoplasm of the macrophages and/or monocytes by incubating the microparticles with macrophages and/or monocytes, briefly exposing the cells to a cold temperature, and continuing to culture the cells. The microparticles can be phagocytosed by the macrophages and/or monocytes during initial incubation. The brief exposure to the cold temperature can induce phagosomal rupture and release of the DNA/PC multilayer into the cytoplasm of the cells.

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