The use of polymeric nanoparticles (NPs) as therapeutics has been steadily increasing over past decades. In vivo imaging of NPs is necessary to advance the therapeutic performance. F-19 Magnetic Resonance Imaging (F-19 MRI) offers multiple advantages for in vivo imaging. However, design of a probe for both biodistribution and degradation has not been realized yet. We developed polymeric NPs loaded with two fluorocarbons as promising imaging tools to monitor NP biodistribution and degradation by F-19 MRI. These 200 nm NPs consist of poly(lactic-co-glycolic acid) (PLGA) loaded with perfluoro-15-crown-5 ether (PFCE) and PERFECTA. PERFECTA/PFCE-PLGA NPs have a fractal sphere structure, in which both fluorocarbons are distributed in the polymeric matrix of the fractal building blocks, which differs from PFCE-PLGA NPs and is unique for fluorocarbon-loaded colloids. This structure leads to changes of magnetic resonance properties of both fluorocarbons after hydrolysis of NPs. PERFECTA/PFCE-PLGA NPs are colloidally stable in serum and biocompatible. Both fluorocarbons show a single resonance in F-19 MRI that can be imaged separately using different excitation pulses. In the future, these findings may be used for biodistribution and degradation studies of NPs by F-19 MRI in vivo using "two color" labeling leading to improvement of drug delivery agents. (C) 2019 Published by Elsevier Inc.