Fig. 4. (A and B) Schematic diagram of the structure of a nanolongan and its anticancer mechanism. Nanolongan included inner UCNPs and an outer gel shell. The shell structure was formed by the coordination of Fe³⁺ with the carboxyl groups of the oxidized starch polymer and wrapped with PEI and DMMA. The chemotherapeutic drug Dox was successfully loaded within the shell. The specific uptake pathway of DGU:Fe/Dox nanolongan: DGU:Fe/Dox nanolongan nanoparticles aggregated at the tumour site by passive targeting (EPR effect). Due to the acidic conditions of the tumour micro-environment, the DMMA molecules on the surface of the nanolongan fell off, thereby exposing the PEI molecules, and the charge changed from negative to positive. The proton sponge effect enabled the nanolongan to successfully escape from the lysosome, and then under NIR irradiation, the energy transfer within the UCNP resulted in the deconstruction of the outer shell. Thereby, the anticancer drug Dox and the ROS generated by the Fe²⁺-triggered Fenton reaction were released to synergistically induce apoptosis and ferroptosis. (C) Growth inhibition of 4T1 tumours treated with different formulations after 48 days. (D) Immunohistochemical images of FACL4 and GPX4 in tumour tissues. Reproduced with permission.⁶⁴ Copyright 2019, American Chemical Society.