ABSTRACT
Photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) can cause cancer cell death through an immunogenic process. However, the study of second near-infrared window (NIR-II)-triggered PTT and PDT combined with CDT to induce an immune response has not been recently reported. Here, we integrated gold nanobipyramids and copper sulfide in a core/shell architecture (AuNBP@CuS). The material displays both photodynamic and photothermal properties under irradiation with a NIR-II laser. The released Cu2+ from CuS under an acidic tumor microenvironment can be converted to Cu+ by glutathione following a Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals in the tumor region. Both in vitro and in vivo results demonstrated that such multifunctional nanoplatforms could achieve enhanced efficiency for image-guided tumor suppression based on the NIR-II photo/chemodynamic therapy. We found that damage-associated molecular pattern molecules such as adenosine triphosphate, pre-apoptotic calreticulin, and high mobility group box-1 in dying cells induced by the NIR-II photo/chemodynamic therapy could simultaneously trigger adaptive immune responses. This is the first report revealing that NIR-II photo/chemodynamic therapy based on AuNBP@CuS had promising performance on tumor suppressor with an effective immunogenic cell death process. STATEMENT OF SIGNIFICANCE: 1. AuNBP@CuS displays both NIR-II photodynamic and photothermal properties. 2. Cu+ following a Fenton-like reaction to generate highly toxic hydroxyl radicals. 3. The NIR-II photo/chemodynamic therapy can trigger adaptive immune responses. 4. Such multifunctional nanoplatforms could achieve enhanced efficiency for tumor suppression.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Cell Line, Tumor , Copper/chemistry , Copper/pharmacology , Gold/chemistry , Gold/pharmacology , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Neoplasms/immunology , Phototherapy/methods , Sulfides/chemistry , Sulfides/pharmacology , Theranostic Nanomedicine/methods , Tumor Microenvironment , Photochemotherapy/methodsABSTRACT
Thermoradiotherapy acts as an important antitumor modality because heating can increase the blood flow and improve the oxygen level in tumor, thus remission of hypoxia-associated resistance for radiotherapy (RT). However, most agents for thermoradiotherapy are used either in the first near-infrared biological window or low photothermal conversion efficiency. Here, a facile method to prepare CuxS/Au nanocomposites via reduction methods from CuxS templates in mild synthetic conditions (i.e., aqueous solution and room temperature) is presented. After the growth of Au nanoparticles, the CuxS/Au nanocomposites have greater benefits for photothermal efficiency than that of CuxS nanoparticles due to the enhanced absorbance in the second near-infrared window. Moreover, biocompatibility and stability of these nanocomposites are greatly improved by lipoic acid poly(ethylene glycol). After the tumors were irradiated with a 1064 nm laser, their oxygenation status is subsequently improved, and the combination of photothermal therapy and RT achieves remarkable synergistic therapeutic effects. This work provides a novel idea to design a new-generation nanomedicine for tumor thermoradiotherapy.