Self-immolative polymers (SIPs) allow a triggered depolymerization, which is an effective way to control the function of polymer-based systems. In this work, hydrophobic SIP segments and hydrophilic polyethylene glycol (PEG) are combined in diblock and triblock amphiphilic architectures, and the SIP-based blocks are made of polycaprolactone-like backbones with UV-sensitive nitrobenzene pendant groups. The depolymerization of the designed architectures in solution is monitored by NMR, UV–vis spectroscopy, and size exclusion chromatography, showing complete cleavage of the triggering units in the SIP parts after about 25 min under UV irradiation and depolymerization rates of the SIP backbones up to 60%. Self-assemblies are prepared from the diblock copolymers, their stability is verified by DLS, and the UV-triggered disintegration of the self-assemblies is demonstrated by SEM, Tindall effect, and by monitoring the derived count rate in DLS, showing a rapid disintegration (after 2 to 6 min under UV light). These SIP-based structures allow a fast, controlled, and on-demand disintegration of self-assemblies, with the ability to encapsulate and release on-demand the Nile red as a hydrophobic model molecule.