Layer-by-Layer Multitargeting Strategy for Enhanced Photothermal Therapy

Photothermal therapy (PTT) presents unique advantages, including high temporal and spatial controllability and relatively few toxic side effects. Active targeting modifications of photothermal agents can deliver nanoprobes to tumors more efficiently, reducing toxic side effects while improving efficacy. In this work, the polyphenols, gallic acid, folic acid (FA), hyaluronic acid (HA), and Fe(III) were selected to prepare a self-photothermal nanoplatform Ga/Fe/HA/FA based on polyphenol-metal self-assembly. The self-assembly process synchronously integrated the targeting molecules, folic acid and hyaluronic acid, layer by layer in a polyphenol–metal network, thus realizing the "layer-by-layer targeting" effect. Compared with the traditional targeting modification, the self-assembly multitargeting modification strategy effectively avoided the complicated experimental steps of traditional targeting modification. Meanwhile, it mitigated the off-target risk during blood circulation and improved tumor-targeting efficiency, ultimately augmenting the effectiveness of photothermal therapy.