Abstract: Nucleic acid drug carriers comprise a nucleic acid carrier complexed with a drug, wherein the nucleic acid carrier and the drug are associated non-covalently, and optionally other agents such as spacer, transfection agents, and targeting agents. The nucleic acid drug complex are discovered to have permissive or refractory uptake depending on many factors including cell type, proliferation rate, among others. The refractive uptake of the nucleic acid drug complex are shown to be useful in the nucleic acid targeting of drugs, both in vitro and in vivo. Novel drug compositions are disclosed that effectively reduce the toxicity of drugs while maintaining drug activity and enhancing a drug's therapeutic index.

Abstract: The present invention relates to compositions that enhance the intracellular delivery of polynucleotides. The present invention is applicable to the fields of gene therapy and oligonucleotide or DNA therapy. Synthetic methods are disclosed, wherein a polynucleotide can be incorporated into the PEG shielded micelle particle to facilitate the delivery of the polynucleotide across a cellular membrane. Incorporation of the polynucleotide into the shielded micelle particle is provided by covalent and non-covalent means. Other cell targeting agents are provided that may also be covalently coupled to the shielded micelle particle to enhance localization in the body. The compositions herein are suitable for pharmaceutical use but are also suitable as transfection agents for in-vitro or in-vivo research. The PEG shielded polynucleotide micelles can provide favorable pharmacokinetic properties such as enhanced uptake into cancer cells, stability against nucleases, high solubility, and non-binding to serum proteins.