A multifunctional nanoplatform with four-in-one photoresponsive functionalities has been achieved through the co-encapsulation of two chromo-fluorogenic components within biocompatible polymeric nanoparticles. This engineered nanoconstruct efficiently delivers different photosensitizers in melanoma cells, which can be detected through their dual-color fluorescence, and induces amplified cell mortality due to the simultaneous photogeneration of singlet oxygen and nitric oxide.