Photothermally Responsive Conjugated Polymeric Singlet Oxygen Carrier for Phase Change-Controlled and Sustainable Phototherapy for Hypoxic Tumor

Hypoxia significantly compromises the therapeutic performance of photodynamic therapy (PDT) owing to the oxygen level which plays a key role in the production of singlet oxygen ((1)O(2)). Herein, the photothermally responsive phase change materials (PCM) are used to encapsulate 1,4-dimethylnaphthalene-functionalized platinum(II)-acetylide conjugated polymer (CP1) with intense near-infrared (NIR) absorption to prepare new (1)O(2) nanocarriers (CP1-NCs). The 1,4-dimethylnaphthalene moieties in CP1-NCs can trap the (1)O(2) produced from CP1 under irradiation and form a stable endoperoxide. Then, the endoperoxide undergoes cycloreversion to controllably release (1)O(2) via the NIR light-triggered photothermal effect of CP1 and controllable phase change of PCM, which can be used for oxygen-independent PDT for hypoxic tumor. Furthermore, the in vivo luminescence imaging-guided synergistic PDT and photothermal therapy showed better efficiency in tumor ablation. The smart design shows the potent promise of CP1-NCs in PCM-controlled and sustainable phototherapy under tumor hypoxic microenvironment, providing new insights for constructing oxygen-independent precise cancer phototherapeutic platform.