Intelligent Nanotransducer for Deep-Tumor Hypoxia Modulation and Enhanced Dual-Photosensitizer Photodynamic Therapy

Upconversion nanoparticles (UCNPs) emerged as promising near-infrared (NIR) light-triggered nanotransducers for photodynamic therapy (PDT). However, the traditionally used 980 nm excitation source could cause an overheating effect on biological tissues, and the single photosensitizer (PS) loading could not efficiently utilize multiradiation UC luminescence, resulting in a limited efficiency of PDT in tumor tissues with hypoxia characteristics. Herein, 808 nm light-responsive Nd-sensitized UCNPs@mSiO₂@MnO₂ core-shell NPs were designed as light nanotransducers with efficient UC emission at 550 and 650 nm for PDT and downshifting luminescence at 1525 nm for second NIR (NIR-II) imaging. UC emission was fully utilized by loading dual PSs, rose bengal (RB), and zinc phthalocyanine (ZnPc), thus significantly improving the reactive oxide species (ROS) generation efficiency. Moreover, a manganese dioxide (MnO₂) shell with ultrasensitive biodegradability in an acidic tumor microenvironment (TME) can generate an amount of oxygen molecules, alleviating the symptoms of hypoxia and then improving the efficacy of PDT. Meanwhile, the biodegraded Mn²⁺ ions can further strengthen T₁-weighted magnetic resonance imaging (MRI). This work presented a new multifunctional theranostic agent for combining NIR-II/MRI imaging and 808 nm light-triggered PDT to combat the limitations of cancer therapy.