Triphenylphosphonium-Functionalized Gold Nanorod/Zinc Oxide Core-Shell Nanocomposites for Mitochondrial-Targeted Phototherapy.

Phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), combined with novel all-in-one light-responsive nanocomposites have recently emerged as new therapeutic modalities for the treatment of cancer. Herein, we developed novel all-in-one triphenylphosphonium-functionalized gold nanorod/zinc oxide core-shell nanocomposites (CTPP-GNR@ZnO) for mitochondrial-targeted PTT/PDT owing to their good biocompatibility, tunable and high optical absorption, photothermal conversion efficiency, highest reactive oxygen species (ROS) generation, and high mitochondrial-targeting capability. Under laser irradiation of 780 nm, the CTPP-GNR@ZnO core-shell nanocomposites effectively produced heat in addition to generating ROS to induce cell death, implying a synergistic effect of mild PTT and PDT in combating cancer. Notably, the in vitro PTT/PDT effect of CTPP-GNR@ZnO core-shell nanocomposites exhibited effective cell ablation (95%) and induced significant intracellular ROS after the 780 nm laser irradiation for 50 min, indicating that CTPP in CTPP-GNR@ZnO core-shell nanocomposites can specifically target the mitochondria of CT-26 cells, as well as generate heat and ROS to completely kill cancer cells. Overall, this light-responsive nanocomposite-based phototherapy provides a new approach for cancer synergistic therapy.

Mesoporous Silica-Layered Gold Nanorod Core@Silver Shell Nanostructures for Intracellular SERS Imaging and Phototherapy.

Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed a new type of mesoporous silica-layered gold nanorod core@silver shell nanostructures loaded with methylene blue (GNR@Ag@mSiO2-MB) as a multifunctional nanotheranostic agent for intracellular SERS imaging and phototherapy. The synthesized GNR@Ag@mSiO2-MB nanostructures possessed a uniform core-shell structure, strong near-infrared (NIR) absorbance, photothermal conversion efficiency (65%), dye loading ability, SERS signal, and Raman stability under phototherapy conditions. Under single 785 nm NIR laser irradiation, the intracellular GNR@Ag@mSiO2-MB nanostructures were dramatically decreased to <9%, which showed excellent photothermal and photodynamic effects toward cancer cell killing, indicating that the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) of the GNR@Ag@mSiO2-MB nanostructures could greatly enhance the therapeutic efficacy of cancer cell death. GNR@Ag@mSiO2-MB nanostructures demonstrated a strong Raman signal at 450 and 502 cm-1, corresponding to the δ(C-N-C) mode, suggesting that the Raman bands of GNR@Ag@mSiO2-MB nanostructures were more efficient to detect CT-26 cell SERS imaging with high specificity. Our results indicate that GNR@Ag@mSiO2-MB nanostructures offer an excellent multifunctional nanotheranostic platform for SERS imaging and synergistic anticancer phototherapy in the future.

Antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells for synergistic chemo-photothermal therapy of drug-resistant bacterial infection.

Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.

Methylene Blue-Loaded Mesoporous Silica-Coated Gold Nanorods on Graphene Oxide for Synergistic Photothermal and Photodynamic Therapy.

Photo-nanotheranostics integrates near-infrared (NIR) light-triggered diagnostics and therapeutics, which are combined into a novel all-in-one phototheranostic nanomaterial that holds great promise for the early detection and precise treatment of cancer. In this study, we developed methylene blue-loaded mesoporous silica-coated gold nanorods on graphene oxide (MB-GNR@mSiO2-GO) as an all-in-one photo-nanotheranostic agent for intracellular surface-enhanced Raman scattering (SERS) imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer. Amine functionalization of the MB-GNR@mSiO2 surfaces was performed using 3-aminopropyltriethoxysilane (APTES), which was well anchored on the carboxyl groups of graphene oxide (GO) nanosheets uniformly, and showed a remarkably higher photothermal conversion efficiency (48.93%), resulting in outstanding PTT/PDT for cancer. The in vitro photothermal/photodynamic effect of MB-GNR@mSiO2-GO with laser irradiation showed significantly reduced cell viability (6.32%), indicating that MB-GNR@mSiO2-GO with laser irradiation induced significantly more cell deaths. Under laser irradiation, MB-GNR@mSiO2-GO showed a strong SERS effect, which permits accurate cancer cell detection by SERS imaging. Subsequently, the same Raman laser can focus on highly detected MDA-MB-23l cells for a prolonged time to perform PTT/PDT. Therefore, MB-GNR@mSiO2-GO has great potential for precise SERS imaging-guided synergistic PTT/PDT for cancer.

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages.

A major limitation in anti-tuberculosis drug screening is the lack of reliable and scalable models for homogeneous human primary macrophage cells of non-cancer origin. Here we report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular Mycobacterium tuberculosis (Mtb). More importantly, iMAC production was amenable to scale up. To evaluate iMAC efficiency in high-throughput anti-tuberculosis drug screening, we performed a phenotypic screening against intracellular Mtb, involving a library of 3,716 compounds that included FDA-approved drugs and other bioactive compounds. Our primary screen identified 120 hits, which were validated in a secondary screen by dose-intracellular and -extracellular Mtb assays. Our confirmatory studies identified a novel anti-Mtb compound, 10-DEBC, also showing activity against drug-resistant strains.