Provided herein are hyperbranched polyaminoglycosides, where in some embodiments, the hyperbranched polyaminoglycosides are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of hyperbranched polyaminoglycosides. In some embodiments, the covalently modified hyperbranched polyaminoglycosides may be tailored to release nitric oxide in a controlled manner and are useful for eradication of both gram positive and gram negative bacteria as well as other microbes.