An all-in-one nanoplatform with near-infrared light promoted on-demand oxygen release and deep intratumoral penetration for synergistic photothermal/photodynamic therapy

Hypoxia and high-density extracellular matrix within the tumor microenvironment (TME) strengthens tumor resistance to the oxygen-dependent cancer therapy. Herein, an on-demand oxygen released nanoplatform (MONs/IR780/PFC-O2@BSA, BMIPO) that was triggered by near-infrared (NIR) light combined with TME has been designed for achieving synergistic photothermal/photodynamic therapy with deep intratumoral penetration and oxygen self-sufficiency. Notably, the zeta potential and transmission electron microscope (TEM) results indicated that such "smart" BMIPO nanoplatform possessed good colloidal stability and on-demand TME-specific degradability. This characteristic of the BMIPO nanoplatform allows it to simultaneously achieve high tumor accumulation and deep intratumoral penetration. The results of the O2 loading and release measurements showed that the as- prepared BMIPO possessed excellent O2 reversibly bind/release performance. Furthermore, the photothermal effect of NIR dye (IR780) accelerated the dissociation of TME-responsive BMIPO, as a result, it achieved an on-demand, continuous and complete O2 release to relieve tumor hypoxia during phototherapy. In vitro and in vivo results demonstrated that the as-prepared all-in-one nanoplatform have successfully realized NIR-triggered on-demand O2 release, nanocarrier-mediated glutathione (GSH) reducing, hyperthermia-promoted deep intratumoral penetration and dual-model imaging-guided precise cancer therapy. This work would provide inspiration for the design of nanoplatforms with on-demand release and deep intratumoral penetration for achieving high-efficiency synergistic photothermal/photodynamic therapy in hypoxic tumors.