Efficient and safe delivery of anticancer drugs such as 5-fluorouracil (5-FU) is still a challenge in chemotherapy. The combination of polymers with a luminescent probe offers a promising venue to develop nanoobjects for theranostics. Herein, upconversion nanoparticles (UCNPs) decorated with polymers based on N-(2-hydroxypropyl) methacrylamide at their surface were investigated as potential carriers of 5-FU. The hyperbranched topology of the polymer offered a higher loading capacity of the polymer shell as compared to this linear analog even though the loading in 5-FU remained low and its release was fast (few hours). To overcome these limitations, 5-FU was conjugated to the polymer through esterification leading to a four-fold increase of the loading and a more sustained release over few days. The introduction of branching points with a disulfide bridge on the polymer afforded nanohybrids susceptible to degradation in the reductive environment of cancer cells. The degradation of the polymer was confirmed by incubating the polymer with dithiothreitol. These results pave the way to theranostics through the use of luminescent properties of UCNPs and the tuning of the polymer architecture.