Provided herein are nanoparticle conjugated synthetic opioid prodrugs that target the peripheral mu opioid receptor (MOR). The prodrugs exhibit long-lived bioavailability, do not compromise the analgesic effects of opioids administered for pain relief (and in some cases can be used for pain relief), and do not induce opioid withdrawal symptoms, when their use is discontinued. Certain of the prodrugs are especially useful for the prevention and/or treatment of unwanted opioid-induced side effects such as opioid-induced constipation (OIC).