Self-Assembled Responsive Bilayered Vesicles with Adjustable Oxidative Stress for Enhanced Cancer Imaging and Therapy

In the present study, we report the development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (Fe₃O₄-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy. The amphiphilic Fe₃O₄-Au JNPs were grafted with poly(ethylene glycol) (PEG) on the Au surface and ROS-generating poly(lipid hydroperoxide) (PLHP) on the Fe₃O₄ surface, respectively, which were then assembled into vesicles containing two closely attached Fe₃O₄-Au NPs layers in opposite directions. The self-assembly mechanism of the bilayered vesicles was elucidated by performing a series of numerical simulations. The enhanced optical properties of the bilayered vesicles were verified by the calculated results and experimental data. The vesicles exhibited enhanced T₂ relaxivity and photoacoustic properties over single JNPs due to the interparticle magnetic dipole interaction and plasmonic coupling. In particular, the vesicles are pH responsive and disassemble into single JNPs in the acidic tumor environment, activating an intracellular biochemical reaction between the grafted PLHP and released ferrous ions (Fe²⁺) from Fe₃O₄ NPs, resulting in highly efficient local ROS generation and increased intracellular oxidative stress. In combination with the release of doxorubicin (DOX), the vesicles combine ROS-mediated cytotoxicity and DOX-induced chemotherapy, leading to greatly improved therapeutic efficacy than monotherapies. High tumor accumulation efficiency and fast vesicle clearance from the body were also confirmed by positron emission tomography (PET) imaging of radioisotope ⁶⁴Cu-labeled vesicles.