Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Gold nanobipyramid@copper sulfide nanotheranostics for image-guided NIR-II photo/chemodynamic cancer therapy with enhanced immune response.

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.

All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

Pre- and post-irradiation mild hyperthermia enabled by NIR-II for sensitizing radiotherapy.

The clinical application of cancer radiotherapy is critically impeded by hypoxia-induced radioresistance, insufficient DNA damage, and multiple DNA repair mechanisms. Herein we demonstrate a dual-hyperthermia strategy to potentiate radiotherapy by relieving tumor hypoxia and preventing irradiation-induced DNA damage repair. The tumor hyperthermia temperature was well-controlled by a near infrared laser with minimal side effects using PEGylated nanobipyramids (PNBys) as the photo-transducer. PNBys have narrow longitudinal localized surface plasmon resonance peak in NIR-II window with a high extinction coefficient (2.0 × 1011 M-1 cm-1) and an excellent photothermal conversion efficiency (44.2%). PNBys-induced mild hyperthermia (MHt) prior to radiotherapy enables vessel dilation, blood perfusion, and hypoxia relief, resulting in an increased susceptibility of tumor cells response to radiotherapy. On the other hand, MHt after radiotherapy inhibits the repair of DNA damage generated by irradiation. The PNBys exert hierarchically superior antitumor effects by the combination of MHt pre- and post-radiotherapy in murine mammary tumor EMT-6 model. Consequently, different from the simple combination of RT and MHt, the coupling of pre- and post-MHt with RT by PNBys open intriguing avenues towards new promising antitumor efficacy.

Nanoplatforms with Remarkably Enhanced Absorption in the Second Biological Window for Effective Tumor Thermoradiotherapy.

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.