The recent discovery of cellular endogenous oligonucletides (ONs) such as antisense ODNs, siRNAs and microRNAs (miRs)--short DNA and RNA sequences that regulate their translation rate by binding to target mRNAs--has broadened the potential application of oligonucleotide-based therapeutic approaches. Alterations in cellular levels of ONs are mechanistically relevant to malignant transformation through deregulation of target oncogene or tumor suppressor gene expression in human malignancies. Despite these novel strategies, however, the problem of efficient delivery of oligonucleotide compounds remains unsolved. Multi-functional nanoparticles, defined as nanoscale particulate entities designed for overcoming various barriers in drug delivery, can be regarded as a possible solution to this problem. We formulate several ONs such as CpG-ODN and miR-29b into leukemia-targeted lipopolyplexes with PEG coating and antibody targeting. Characterization and transfection efficiency are evaluated. Particle size and zeta-potential are also measured. Using several leukemia cell lines as a model, cell viability and gene transfection efficiency as well as protein down regulation are examined. In addition to in vitro study, leukemia cells are implanted into nude mice to grow solid tumor and immunolipopolyplexes are injected. Measurements of tumor size and mice survival rate, analysis of the mRNA and protein down regulation in tumor tissue by cell and molecular level, and pharmacokinetics study for nanoparticles are also carried out. We compare the transfection efficiency and cytotoxicity of free ONs and their nanoparticles both in vitro and in vivo.

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