NIR-II Absorbed Dithienopyrrole-Benzobisthiadiazole Based Nanosystems for Autophagy Inhibition and Calcium Overload Enhanced Photothermal Therapy.

Although the current cancer photothermal therapy (PTT) can produce a powerful therapeutic effect, tumor cells have been proved a protective mechanism through autophagy. In this study, a novel hybrid theranostic nanoparticle (CaCO3@CQ@pDB NPs, CCD NPs) is designed and prepared by integrating a second near-infrared (NIR-II) absorbed conjugated polymer DTP-BBT (pDB), CaCO3, and autophagy inhibitor (chloroquine, CQ) into one nanosystem. The conjugated polymer pDB with asymmetric donor-acceptor structure shows strong NIR-II absorbing capacity, of which the optical properties and photothermal generation mechanism of pDB are systematically analyzed via molecular theoretical calculation. Under NIR-II laser irradiation, pDB-mediated PTT can produce powerful killing ability to tumor cells. At the same time, heat stimulates a large amount of Ca2+ inflow, causing calcium overload induced mitochondrial damage and enhancing the apoptosis of tumor cells. Besides, the released CQ blocks the self-protection mechanism of tumor cells and greatly enhances the attack of PTT and calcium overload therapy. Both in vitro and in vivo experiments confirm that CCD NPs possess excellent NIR-II theranostic capacity, which provides a new nanoplatform for anti-tumor therapy and builds great potential for future clinical research.

Naphthalene Diimide-Based Polycyclic Conjugated Molecule Composite CoFe2O4 Nanohybrids for Photoacoustic Imaging-Mediated Photo-/Sonic Therapy.

The complex and harsh tumor microenvironment imped the efficacy of single-modality tumor therapy. With the advantages of biosafety, organic/inorganic nanohybrids have attracted more and more interest of researchers, and it is critical to investigate the development of highly efficient nanohybrids for multimodality combination therapy of cancers. Herein, a naphthalene diimide-based polycyclic conjugated molecule (NDI-S) is designed and synthesized, which has broader light absorption in the near infrared (NIR) region, outstanding photothermal conversion ability, and excellent photostability. Inorganic CoFe2O4 is synthesized via a solvothermal technique, which can produce much more reactive oxygen species (ROS) as a sonosensitizer when activated by ultrasonic (US). NDI-S and CoFe2O4 are then nanoprecipitated to create the organic/inorganic nanohybrids, NDI-S@CoFe2O4. According to the results of in vitro and in vivo experiments, NDI-S@CoFe2O4 can serve as a multifunctional nanoplatform for multimodal treatment of tumors in combination with photothermal/photodynamic/sonodynamic- therapy under the guidance of photoacoustic imaging, which provides a new vision of the development of organic/inorganic nanohybrids for cancer theranostics.