Stimulus-Responsive Polymersomes Loaded with NaErF4@CaF2 Nanoparticles for Precise NIR Lifetime-Based Detection of Microenvironment pH Changes.

External stimulus-responsive nanoplatforms based on biodegradable co-polymers and surfactants were loaded with luminescent nanoparticles for dynamic lifetime-based monitoring of pH changes in solution. In particular, we used PEG-PLGA-based blocks co-stabilized with either amphoteric coco-betaine or nonionic Pluronic F-127 to form higher-order clustered structures, i.e., polymersomes. The average vehicle size was in the nanometer range, and the obtained structures showed prolonged colloidal stability, with high ζ-potential and low polydispersity index. Next, the luminescent NaErF4@CaF2 nanoparticles were used as an inside cargo and efficiently loaded within the cores of polymersomes. The selection of high Er3+ ion doping in core nanoparticles, together with heterogeneous shelling, allowed for intense emission in the NIR region with prolonged luminescence lifetimes exhibited by this material. The selection of the nanoparticles was dictated by their known water sensitivity, manifesting in luminescence lifetime shortening in the NIR range. Thus, in the next step, as the building structure of polymersomes itself was pH-sensitive, owing to the PLGA polymer used, the dynamic lifetime-based monitoring of nanovehicle dissolution was achieved via interactions between water molecules and luminescent nanoparticle surface. The presented results constitute engineered nanostructures with high future potential for background-free monitoring of pH-responsive processes including nanomedicine-based therapies across a wide range of tumors.