Erythrocyte Membrane Camouflaged Nanotheranostics for Optical Molecular Imaging-Escorted Self-Oxygenation Photodynamic Therapy.

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O 2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H 2 O 2 ) will be decomposed by CAT to produce O 2 , which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen ( 1 O 2 ). The 1 O 2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.