Tumor microenvironment-activated self-charge-generable metallosupramolecular polymer nanocapsules for photoacoustic imaging-guided targeted synergistic photothermal-chemotherapy

Abstract An integrated nanosystem of target, visualization, high circulation stability, and multi-therapy effects represents the leading direction of next generation anti-cancer strategy. Nevertheless, this normally requires elegant multi-component and hierarchical structure design of nanomaterials, or even a complicated post-treatment procedure, to combine different functions together. Herein, we show that hollow metallosupramolecular polymer nanoparticles (HMPNs) derived from a selective-etching approach based on Kirkendall effect have combined capabilities of (i) facile in-situ guest cargo encapsulation, (ii) reversible surface charge evolution, (iii) excellent photoacoustic property and (vi) highly synergistic photothermal-chemo therapeutic effect. Using DOX as a model drug, we can easily fabricate DOX-HMPNs because the etching process is accompanied with effective matter exchange between outer environment and inner particle, while significantly avoiding the premature drug leakage. Notably, synergistic effect between reversible phenolic hydroxyl ionization and dynamic catechol-FeIII coordination endows DOX-HMPNs with dramatic self-charge generation ability, thus achieving weakly acidic tumor microenvironment-activated reversible surface charge evolution. We have found that DOX-HMPNs with this self-charge generation feature can effectively achieve prolonged circulation and tumor recognition. Moreover, the cleavage of imine bond can induce the disassembly of hollow particles in strongly acidic lysosomes, and thus accelerate the release of DOX. This chemotherapy, in combination with the cascade-responsive behavior and photothermal/photoacoustic properties of HMPNs, makes our DOX-HMPNs exhibit synergistic antitumor efficiency and provide promising potential for cancer theranostic application.