Tumor-Activated Nanoassemblies with Positive Feedback Loop for Photoacoustic Imaging-Guided Precise Cancer Therapy

To realize highly selective/sensitive tumor microenvironment (TME) activated precise cancer therapy, a phosphomolybdate/metal–organic framework composite (PMo/MIL-101-Fe, P/M) has been designed for acidic/reductive TME activated photoacoustic imaging (PAI)-guided photothermal therapy (PTT) and TME regulatory enhanced chemodynamic therapy (CDT). The P/M composite incorporates Keggin-type phosphomolybdate into the porous MIL-101-Fe framework, enabling targeted degradation within the reductive TME and then releasing reduced PMo and Fe²⁺. The reduced PMo self-assembles into large clusters, leading to enhanced tumor retention, amplified PAI signals, and effective photothermal therapy (PTT). Concurrently, the liberated Fe²⁺ efficiently catalyzes H₂O₂ to generate hydroxyl radicals (^•OH), contributing to CDT. Notably, the depletion of glutathione (GSH) by both MIL-101-Fe and PMo further augments the efficacy of CDT. As a result, this composite enables improved antitumor effects both in vitro and in vivo. This work provides a promising avenue to produce TME specifically activated precise nanotheranostic paradigms through rationally designed nanostructures.