Erythrocyte membrane-camouflaged carrier-free nanoassembly of FRET photosensitizer pairs with high therapeutic efficiency and high security for programmed cancer synergistic phototherapy

Phototherapy has been intensively investigated as a non-invasive cancer treatment option. However, its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity. To achieve high efficiency security, nanoassembly of Forster Resonance Energy Transfer (FRET) photosensitizer pairs developed on basis dual-mode co-loading photocaging strategy. For proof-of-concept, an erythrocyte-camouflaged FRET pair co-assembly chlorine e6 (Ce6, donor) 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, acceptor) for breast treatment. Notably, Ce6 in the nanoassemby quenched DiR could be unlocked photodynamic therapy (PDT) only when photobleached 808-nm laser. As result, Ce6-caused phototoxicity well controlled. Under cascaded laser irradiation (808–660 nm), tumor-localizing temperature rise following not induces tumor cell apoptosis but also facilitates penetration NPs, relieves hypoxia, promotes PDT Ce6. Such pair-based provides new strategy developing multimodal phototherapy nanomedicines with good security. • Biomimetic carrier-free pairs. Dual-mode programmed synergistic phototherapy. Avoiding ROS-induced off-target intelligently controlled ROS activation.