Due to specific immune recognition receptors on the surface of T cells, their membranes are promising mimic nanocarriers for delivering drugs to tumor lesions. However, this single targeting strategy potentially compromises therapy efficacy for tumor targeting due to inter‐ and intra‐heterogeneity of tumors. Azide (N ₃ ) or bicyclo [6.1.0] nonyne (BCN) modified unnatural sugars can be successfully incorporated into surface glycans of various tumor cells as artificial receptors, which is expected to overcome the insufficiency of single targeting. Based on this artificial tumor targeting strategy, indocyanine green nanoparticles (INPs) coated with N ₃ ‐labeled T cell membrane (N ₃ ‐TINPs) are constructed, which can specifically target the natural antigen and BCN artificial receptors on tumors through immune recognition and bioorthogonal chemistry, respectively. The results show that the fluorescence intensity in the tumors of mice treated with N ₃ ‐TINPs is 1.5 fold compared with that of the mice treated with unlabeled TINPs. The accumulated N ₃ ‐TINPs in the tumor significantly increase the photothermal therapeutic effect without adverse effect. Therefore, this T cell membrane mimicking nanoparticles based bioorthogonal chemistry may provide an alternative artificial targeting strategy for further tumor targeting photothermal therapy.

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.