Provided herein are biodegradable copolymers and nanoplex delivery systems comprising the same and a cargo molecule, such as a nucleic acid, a polynucleotide or other biomolecule. The biodegradable copolymers may comprise a reducible polymer linearly modified with lysine, such as a linear lysine-modified N,N-cystamine bisacrylamide. The biodegradable copolymers also may be conjugated to a sequestering moiety, such as dietheylamine. The biodegradable copolymers also may comprise one or both of a targeting moiety and one or more moieties to facilitate endosomal escape. Also provided are methods for treating a pathophysiological condition and for increasing biocompatibility of a polymeric delivery system upon delivery to a subject using the biodegradable copolymers and nanoplexes.
