Molecular compositions, nanoparticle compositions, and pharmaceutical compositions of the invention provide for the delivery of a polynucleotide to a hypoxic cell or tissue. The compositions can also be used for the delivery a hydrophobic pharmaceutical agent, either alone or in combination with a polynucleotide, to a hypoxic cell or tissue. Methods of making such compositions and methods of using such composition to treat a condition associated with a hypoxic cell or tissue are provided as well. Also provided are kits for use in treating a condition associated with a hypoxic cell or tissue.