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.

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Metal complexes are widely used as anticancer drugs, while the severe side effects of traditional chemotherapy require new therapeutic modalities. Sonodynamic therapy (SDT) provides a significantly noninvasive ultrasound (US) treatment approach by activating sonosensitizers and initiating reactive oxygen species (ROS) to damage malignant tissues. In this work, three metal 4‐methylphenylporphyrin (TTP) complexes (MnTTP, ZnTTP, and TiOTTP) are synthesized and encapsulated with human serum albumin (HSA) to form novel nanosonosensitizers. These nanosonosensitizers generate abundant singlet oxygen (1O2) under US irradiation, and importantly show excellent US‐activatable abilities with deep‐tissue depths up to 11 cm. Compared to ZnTTP‐HSA and TiOTTP‐HSA, MnTTP‐HSA exhibits the strongest ROS‐activatable behavior due to the lowest highest occupied molecular orbital−lowest unoccupied molecular orbital gap energy by density functional theory. It is also effective for deep‐tissue photoacoustic/magnetic resonance dual‐modal imaging to trace the accumulation of nanoparticles in tumors. Moreover, MnTTP‐HSA intriguingly achieves high SDT efficiency for simultaneously suppressing the growth of bilateral tumors away from ultrasound source in mice. This work develops a deep‐tissue imaging‐guided SDT strategy through well‐defined metalloporphyrin nanocomplexes and paves a new way for highly efficient noninvasive SDT treatments of malignant tumors.

Micro/nanorobots have the potential to be remotely propelled and manipulated in complex biological fluid and organ tissue. However, the combination of the sophisticated physiological barriers, remote‐controlled navigation, real‐time motion tracking, and diagnostic/therapeutic effects are tremendous challenges for application and translation. An unique sequential magneto‐actuated and optics‐triggered biomicrorobot (AI microrobot) for actively targeted cancer treatment is prepared. The AI microrobot consists of two components, magnetospirillum magneticum (AMB‐1), providing the ability to autonomously swim toward the tumor site via internal hypoxia‐driven effects and an external applied magnetic field, and indocyanine green nanoparticles, acting as a fluorescence imaging agent and photothermal therapy. The AI microrobots are tracked in vivo by fluorescence and magnetic resonance imaging. It is found that the AI microrobots can sequentially migrate to the hypoxic internal area of tumors and then effectively eradicate solid tumors through photothermal therapy under NIR laser irradiation. The sequential magneto‐actuated and optics‐triggered AI microrobots platform described here presents a bioinspired strategy toward remotely controlled propulsion, actively targeted cargo delivery, and satisfactory therapeutic performance in the circulatory system.