Single wavelength light-mediated, synergistic bimodal cancer photoablation and amplified photothermal performance by graphene/gold nanostar/photosensitizer theranostics.

Light-triggered nanotheranostics opens a fascinating but challenging avenue to achieve simultaneous and highly efficient anticancer outcomes for multimodal therapeutic and diagnostic modalities. Herein, a multifunctional phototheranostics based on a photosensitizer-assembled graphene/gold nanostar hybrid (GO/AuNS-PEG) was developed for cancer synergistic photodynamic (PDT) and photothermal therapy (PTT) as well as effective photothermal imaging. The stable and biocompatible GO/AuNS-PEG composite displayed a high photothermal conversion efficiency due to the enhanced optical absorbance of both graphene and gold nanostars in the near-infrared (NIR) range. By tuning the absorption wavelength of GO/AuNS-PEG to that of Chlorin e6 (Ce6), GO/AuNS-PEG/Ce6 completely eliminated the EMT6 xenograft tumors by the tremendous synergistic anticancer efficiency of simultaneous PDT and PTT under a single NIR laser irradiation (660nm) in vivo. The underlying mechanism may be the enhanced cytoplasmic uptake and accumulation of GO/AuNS-PEG/Ce6 and the subsequent photodestruction of the lysosomal membrane and mitochondria. Moreover, GO/AuNS-PEG/Ce6 exhibited negligible side-effects on the body and other organs. These results demonstrate that the graphene/gold nanostar nanoconstruct provides a versatile and reliable integrated platform for the photo-controlled cancer theragnostic applications. This work demonstrated the application of graphene-Au Nanostars hybridized system (denoted as GO/AuNS-PEG) in single wavelength laser induced synergistic photodynamic (PDT) and photothermal therapy (PTT) and effective cancer photothermal/fluorescence multimode imaging. GO/AuNS-PEG showed excellent biocompatibility and high dual-enhanced photothermal efficiency under the near-infrared laser irradiation that was very promise for deep tumor imaging. By combining with the photosensitizer Chlorin e6, both in vitro and in vivo data confirmed the efficient photoablation of the EMT6 tumors through the synergistic PDT and PTT effect under the activation of a single wavelength laser.

Wu C ，Li D ，Wang L ，Guan X ，Tian Y ，Yang H ，Li S ，Liu Y ... -  《-》

Hybrid graphene/Au activatable theranostic agent for multimodalities imaging guided enhanced photothermal therapy.

Photothermal therapy (PTT) has been increasingly investigated. However, there are still challenges in strategies that can further enhance photoconversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. Herein, we developed a fluorescent/photoacoustic imaging guided PTT agent by seeding Gold (Au) nanoparticles onto graphene oxide (GO). Near infrared dye (Cy5.5) labeled-matrix metalloproteinase-14 (MMP-14) substrate (CP) was conjugated onto the GO/Au complex (GA) forming tumor targeted theranostic probe (CPGA), whereCy5.5 fluorescent signal is quenched by Surface Plasmon Resonance (SPR) capacity from both GO and Au, yet it can boost strong fluorescence signals after degradation by MMP-14. The photothermal effect of GA hybrid was found significantly elevated compared with Au or GO alone. After intravenous administration of CPGA into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64 ± 0.51 for optical imaging and 2.5 ± 0.27 for PA imaging). The tumors were then irradiated with a laser, and an excellent tumor inhibition was observedwithoutrecurrence. Our studies further encourage applications of the hybrid nanocomposite for image-guided enhanced PTT in biomedical applications, especially in cancer theranostics.

Gao S ，Zhang L ，Wang G ，Yang K ，Chen M ，Tian R ，Ma Q ，Zhu L ... -  《-》

Ce6-Modified Carbon Dots for Multimodal-Imaging-Guided and Single-NIR-Laser-Triggered Photothermal/Photodynamic Synergistic Cancer Therapy by Reduced Irradiation Power.

Sun S ，Chen J ，Jiang K ，Tang Z ，Wang Y ，Li Z ，Liu C ，Wu A ，Lin H ... -  《-》

Intelligent gold nanostars for in vivo CT imaging and catalase-enhanced synergistic photodynamic & photothermal tumor therapy.

Zhang L ，Yang XQ ，Wei JS ，Li X ，Wang H ，Zhao YD ... -  《Theranostics》

PEGylated hydrazided gold nanorods for pH-triggered chemo/photodynamic/photothermal triple therapy of breast cancer.

Integration of multimodal therapies into one nanoplatform holds great promise to overcome the drawbacks of conventional single-modal therapy and pursues enhanced anticancer efficacy. Herein, we developed a PEGylated gold nanorods (GNRs)-based nanoplatform (GNRs-MPH-ALA/DOX-PEG) with pH-responsive drug release property for triple-combined chemotherapy (CT), photodynamic therapy (PDT) and photothermal therapy (PTT) of breast cancer. GNRs were first decorated with mercaptopropionylhydrazide (MPH) and thiol-terminated monomethoxyl poly(ethylene glycol) (mPEG-SH) via Au-thiol linkage, and subsequently conjugated with chemotherapeutant doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (ALA) through acid-liable hydrazone bonds between drugs and MPH molecules. The resulting nanoplatform GNRs-MPH-ALA/DOX-PEG exhibited excellent stability in physiological solutions and pH-responsive DOX and ALA release behaviors. In vitro studies showed that GNRs-MPH-ALA/DOX-PEG could efficiently enter human breast cancer MCF-7 cells and release DOX and ALA into cytoplasm. Furthermore, DOX could locate in the cell nucleus and ALA was productively metabolized into protoporphyrin IX (PpIX). Upon near-infrared (NIR) irradiation, PpIX produced enough reactive oxygen species for PDT and meanwhile GNRs could efficiently induce hyperthermia for PTT. Compared with single CT and dual-modal CT/PDT or CT/PTT treatment, the triple-combined CT/PDT/PTT treatment could more efficiently kill MCF-7 cells via a superadditive antitumor effect. Furthermore, the circulation half-life of GNRs-MPH-ALA/DOX-PEG in the blood was as long as approximately 52 min and it exhibited a tumor accumulation of 3.3%. The triple-combined CT/PDT/PTT treatment could completely suppress tumor growth without obvious systemic toxicity. Our study paves a new avenue for multimodal therapy of breast cancer. STATEMENT OF SIGNIFICANCE: The development of a simple but effective strategy to construct a versatile nanoplatform for multi-combined therapy still remains an enormous challenge. In this work, we developed a novel and simple nanoplatform GNRs-MPH-ALA/DOX-PEG with pH-responsive drug release for triple-combined chemotherapy (CT), photodynamic therapy (PDT) and photothermal therapy (PTT) of breast cancer. The nanoplatform could be efficiently internalized by MCF-7 cells. The intracellular GNRs-MPH-ALA/DOX-PEG could release DOX for CT, induce hyperthermia for PTT and generate high levels of ROS for PTT. Compared with single CT and dual-modal CT/PDT or CT/PTT treatments, the triple-combined CT/PDT/PTT treatment could more efficiently kill MCF-7 cells via a superadditive antitumor effect. Furthermore, upon triple-combined CT/PDT/PTT treatment, the tumor growth was completely suppressed without obvious systemic toxicity.

Xu W ，Qian J ，Hou G ，Wang Y ，Wang J ，Sun T ，Ji L ，Suo A ，Yao Y ... -  《-》