The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.

This work presents a facile means of accessing thio-perylenediimides that not only possess excellent antitumor property but provide a novel proof-of-concept means to improve therapeutic performance via the optimization of non-bonding interactions.

Molecular fluorophores with the second near‐infrared (NIR‐II) emission hold great potential for deep‐tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J‐aggregates are used to construct long‐wavelength NIR‐II emitters as their optical bands show remarkable red shifts upon forming water‐dispersible nano‐aggregates. However, their wide applications in the NIR‐II fluorescence imaging are impeded by the limited varieties of J‐type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J‐aggregate fluorophore (BT6) with anti‐quenching effect is reported for highly efficient NIR‐II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation‐induced emission (AIE) property for conquering the self‐quenching issue of the J‐type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR‐II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole‐body blood vessel and imaging‐guided phototherapy results verify that BT6 NPs are excellent agent for NIR‐II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR‐II J‐aggregates with precisely manipulated anti‐quenching properties for highly efficient biomedical applications.

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca2+) channels is of great significance in the treatment of tumors. Here, a simple ROS generation system is developed to activate ROS-sensitive ion channels for enhancing calcium-cascade-mediated tumor cell death under near-infrared (NIR) light irradiation. Upon irradiation with an 808 nm laser, a low-lethality amount of ROS facilitates plasmid transient potential receptor melastatin-2 (pTRPM2) gene release via cleavage of the Se–Se bonds, which contributed to enhancing the expression of TRPM2 in tumor cells. Meanwhile, ROS could potently activate TRPM2 for Ca2+ influx to inhibit early autophagy and to further induce intracellular ROS production, which ultimately led to cell death in TRPM2 expressing tumor cells. Both in vitro and in vivo data show that nanoparticles have an excellent therapeutic effect on cancer upon NIR light. This work presents a simple modality based on NIR light to remotely control the ROS-sensitive ion channel for cancer therapy.