Porphyrins and their derivatives are widely used as photosensitizers
and sonosensitizers in tumor treatment. Nevertheless, their poor water
solubility and low chemical stability reduce their singlet oxygen
(1O2) yield and, consequently, their photodynamic
therapy (PDT) and sonodynamic therapy (SDT) efficiency. Although strategies
for porphyrin molecule assembly have been developed to augment 1O2 generation, there is scope for further improving
PDT and SDT efficiencies. Herein, we synthesized ordered manganese
porphyrin (SM) nanoparticles with well-defined self-assembled metalloporphyrin
networks that enabled efficient energy transfer for enhanced photocatalytic
and sonocatalytic activity in 1O2 production.
Subsequently, Au nanoparticles were grown in situ on the SM surface by anchoring the terminal alkynyl of porphyrin
to form plasmonic SMA heterostructures, which showed the excellent
near-infrared-II (NIR-II) region absorption and photothermal properties,
and facilitated electron–hole pair separation and transfer.
With the modification of hyaluronic acid (HA), SMAH heterostructure
nanocomposites exhibited good water solubility and were actively targeted
to cancer cells. Under NIR-II light and ultrasound (US) irradiation,
the SMAH generates hyperthermia, and a large amount of 1O2, inducing cancer cell damage. Both in vitro and in vivo studies confirmed that the SMAH nanocomposites
effectively suppressed tumor growth by decreasing GSH levels in SDT-augmented
PDT/PTT. Moreover, by utilizing the strong absorption in the NIR-II
window, SMAH nanocomposites can achieve NIR-II photoacoustic imaging-guided
combined cancer treatment. This work provides a paradigm for enhancing
the 1O2 yield of metalloporphyrins to improve
the synergistic therapeutic effect of SDT/PDT/PTT.