An activation mechanism based on encapsulated ultrasmall gadolinium oxide nanoparticles (Gd oxide NPs) in bioresponsive polymer capsules capable of triggered release in response to chemical markers of disease (i.e., acidic pH, H2O2) is presented. Inside the hydrophobic polymeric matrices, the Gd oxide NPs are shielded from the aqueous environment, silencing their ability to enhance water proton relaxation. Upon disassembly of the polymeric particles, activation of multiple contrast agents generates a strong positive contrast enhancement of >1 order of magnitude.