In photodynamic therapy (PDT), high polydispersity of polymeric carriers and random distribution of loaded photosensitizers (PSs) result in batch-to-batch variabilities. Alternatively, we designed cyclopeptidic photosensitizer prodrugs (cPPPs). These conjugates are perfectly defined, non-toxic and optically extinct in their initial state, reducing the side effects of premature exposure to radiation. Thanks to copper-free click chemistry, we coupled various loading of PSs, quenchers and chemotherapeutic drugs onto constrained scaffolds through protease-sensitive peptidic linkers. In the context of PDT use, relevant cPPPs are activated in vitro by enzymes (e.g., urokinase, cathepsin B) overexpressed by cancer cells (e.g., PC-3, A549), thus favoring a precise targeting of the area to be treated in order to reduce collateral damage. Once irradiated, fragments of interest indicate not only the presence of tumors, but are also toxic to cancer cells. Modulation of PEGylation has been explored to evaluate pharmacokinetics and biodistribution profile in vivo with fertilized hen eggs.