Pt-Te-Nanorod-Based Photothermal Chemokine Immunotherapy for All Stages of Cancer via Adaptive and Innate Immunity.

The chemokine (C-X-C) motif ligand 9 (CXCL9) is one of the lymphocyte-traffic-involved chemokines. Despite the immunotherapeutic potential of CXCL9 for recruiting effector T cells (cluster of differentiation 4+ (CD4+) and CD8+ T cells) and natural killer cells (NK cells) around the tumors, practical applications of CXCL9 have been limited because of its immune toxicity and lack of stability in vivo. To overcome these limitations, we designed and synthesized Pt-Te nanorods (PtTeNRs), which exhibited excellent photothermal conversion efficiency with stable CXCL9 payload characteristics under the physiological conditions of in vivo environments. We developed a CXCL9-based immunotherapy strategy by utilizing the unique physicochemical properties of developed PtTeNRs. The investigation revealed that the PtTeNR-loaded CXCL9 was effectively accumulated in the tumor, subsequently released in a sustained manner, and successfully recruited effector T cells for immunotherapy of the designated tumor tissue. In addition, a synergistic effect was observed between the photothermal (PT) therapy and antiprogrammed cell death protein 1 (aPD-1) antibody. In this study, we demonstrated that PtTeNR-based CXCL9, PT, and aPD-1 antibody trimodal therapy delivers an outstanding tumor suppression effect in all stages of cancer, including phases 1-4 and tumor recurrence.

Rhodium-Tellurium Nanorod Synthesis Using Galvanic Replacement-Polyol Regrowth for Thermo-Dynamic Dual-Modal Cancer Phototherapy.

Rh is a noble metal introduced in bioapplications, including diagnosis and therapy, in addition to its consolidated utilization in organic catalysis and electrocatalysis. Herein, we designed the synthesis of highly crystalline Rh nanocrystal-decorated Rh-Te nanorods (RhTeNRs) through galvanic replacement of sacrificial Te nanorod (TeNR) templates and subsequent polyol regrowth. The obtained RhTeNRs showed excellent colloidal stability and efficient heat dissipation and photocatalytic activity under various laser irradiation wavelengths. Based on the confirmed biocompatibility, RhTeNRs were introduced into in vitro and in vivo cancer phototherapies. The results confirmed the selective physical death of cancer cells in the local area through laser irradiation. While chemotherapy does not guarantee successful treatment due to side effects and resistance, phototherapy using heat and reactive oxygen species generation of RhTeNRs induces physical death.

Osmium-Tellurium Nanozymes for Pentamodal Combinatorial Cancer Therapy.

Although nanoparticles based on Group 8 elements such as Fe and Ru have been developed, not much is known about Os nanoparticles. However, Os-based nanostructures might have potential in various applications including biomedical fields. Therefore, in this study, we synthesized Os-Te nanorods (OsTeNRs) by solvothermal galvanic replacement with Te nanotemplates. We explored the nanozymatic activity of the synthesized OsTeNRs and found that they exhibited superior photothermal conversion and photocatalytic activity. Along with chemotherapy (regorafenib) and immunotherapy, the nanozymatic, photothermal, and photodynamic activities of OsTeNRs were harnessed to develop a pentamodal treatment for hepatocellular carcinoma (HCC); in vitro and in vivo studies demonstrated that the pentamodal therapy could alleviate hypoxia in HCC cells by generating oxygen and reduced unintended drug accumulation in organs. Moreover, bone-marrow toxicity due to regorafenib could be reduced as the drug was released in a sustained manner. Thus, OsTeNRs can be considered as suitable nanotemplates for combinatorial cancer therapy.

Fabrication of Bioprobe Self-Assembled on Au-Te Nanoworm Structure for SERS Biosensor.

In the present study, we propose a novel biosensor platform using a gold-tellurium (Au-Te) nanoworm structure through surface-enhanced Raman spectroscopy (SERS). Au-Tenanoworm was synthesized by spontaneous galvanic replacement of sacrificial Te nanorods templated with Au (III) cations under ambient conditions. The fabricated Au-Te nanoworm exhibited an interconnected structure of small spherical nanoparticles and was found to be effective at enhancing Raman scattering. The Au-Te nanoworm-immobilized substrate exhibited the ability to detect thyroxine using an aptamer-tagged DNA three-way junction (3WJ) and glycoprotein 120 (GP120) human immunodeficiency virus (HIV) using an antibody. The modified substrates were investigated by scanning electron microscopy and atomic force microscopy (AFM). The optimal Au-Te nanoworm concentration and immobilization time for the thyroxine biosensor platform were further determined by SERS experimentation. Thus, the present study showed that the Au-Te nanoworm structure could be applied to various biosensor platforms.

Nonrecurring Circuit Nanozymatic Enhancement of Hypoxic Pancreatic Cancer Phototherapy Using Speckled Ru-Te Hollow Nanorods.

Nanozymatic reactions that produce or consume oxygen (O2) or reactive oxygen species (ROS) consist of oxidase, peroxidase, superoxide dismutase (SOD), and catalase-type activity. Although extensive studies were conducted to overcome hypoxia through nanozymatic reactions, the construction of an ideal system is challenging, given that the reactants and products are arranged in a recurring structure for continuous consumption in a full cycle. In this study, speckled Ru-Te hollow nanorods were prepared through solvothermal galvanic replacement against Te nanorod templates with high yield and robustness. From their multicompositional characteristics, nonrecurring peroxidase-SOD-catalase-type nanozymatic properties were identified with photothermal and photodynamic feasibility over a wide range of laser irradiation wavelengths. Owing to the excellent colloidal stability and biocompatibility, the proposed Ru-Te-based nanozymatic platform was highly effective in hypoxic pancreatic cancer phototherapy in vitro and in vivo by near-infrared laser irradiation mediated photothermal and photodynamic combination treatment.

Environmentally Friendly Synthesis of Au-Te-Clustered Nanoworms via Galvanic Replacement for Wavelength-Selective Combination Cancer Therapy.

Au-Te-clustered nanoworms (AuTeNWs) were successfully synthesized under ambient conditions by spontaneous galvanic replacement using Te nanorods as a sacrificial nanotemplate. Along with the gradual replacement and on-surface crystalline Au cluster formation, Te nanotemplates were transformed into a serpentine nanoworm-like morphology. The present strategy was an environmentally friendly method that did not use surfactants to control the surface structure. The synthesized nanoworms exhibited excellent photothermal conversion, photocatalytic efficiencies, and high payloads for thiolated genes and cell-penetrating peptides. According to the visible and near-infrared wavelengths of light, the photodynamic and photothermal therapeutic pathways were dominantly acting, respectively. From this, wavelength-selective combination treatment with gene therapy was successfully accomplished. Taken together, excellent therapeutic effects for in vitro and in vivo mouse models against hepatitis C replicon human hepatocarcinoma were clearly identified by using the present AuTeNWs as a phototherapeutic nanocarrier.

Synthesis of porous Pd nanoparticles by therapeutic chaga extract for highly efficient tri-modal cancer treatment.

Porous palladium nanoparticles were designed and synthesized to maximize the pharmacological activity of the chaga mushroom (Inonotus obliquus) extract, which has anticancer and antibacterial activities. In the present study, we synthesized anisotropic porous Pd nanostructures with ultraviolet-visible-near infrared whole wavelength region absorption using chaga extract concentration-dependent reductant-mediated synthesis. The porous Pd nanoparticles exhibited a surface chaga extract-derived anticancer effect, controlled delivery of doxorubicin through electrostatic interaction, and a photothermal conversion effect under 808 nm laser irradiation. The combined application of the three cancer treatment approaches clearly demonstrated the feasibility of synergistic tri-modal therapy. The present platform using Pd, which is a key constituent element of nanocatalysts but is not commonly used in biological applications, suggests numerous applications utilizing Pd nanostructures, as well as the potential development of new cancer therapies.