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Synergistic enhancement of immunological responses triggered by hyperthermia sensitive Pt NPs via NIR laser to inhibit cancer relapse and metastasis.

ABSTRACT: The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis. Photothermal therapy (PTT) triggers the release of tumor-specific antigens and damage associated molecular patterns (DAMPs) in-situ. However, the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells. Therefore, systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect. To this end, polyethylene glycol (PEG)-stabilized platinum (Pt) nanoparticles (Pt NPs) conjugated with a PD-L1 inhibitor (BMS-1) through a thermo-sensitive linkage were constructed. Upon near-infrared (NIR) exposure, BMS-1 was released and maleimide (Mal) was exposed on the surface of Pt NPs, which captured the antigens released from the ablated tumor cells, resulting in the enhanced antigen internalization and presentation. In addition, the Pt NPs acted as immune adjuvants by stimulating dendritic cells (DCs) maturation. Furthermore, BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues. Thus, Pt NPs can ablate tumors through PTT, and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration, thereby preventing tumor relapse and metastasis.

SUBMITTER: Yu J

PROVIDER: S-EPMC8379359 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms.

Project description:BackgroundInfectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest.ResultsIn this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo.ConclusionsOur study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

| S-EPMC7158002 | biostudies-literature

Cold atmospheric helium plasma causes synergistic enhancement in cell death with hyperthermia and an additive enhancement with radiation.

Project description:Cold atmospheric plasmas (CAPs) have been proposed as a novel therapeutic method for its anti-cancer potential. However, its biological effects in combination with other physical modalities remain elusive. Therefore, this study examined the effects of cold atmospheric helium plasma (He-CAP) in combination with hyperthermia (HT) 42 °C or radiation 5 Gy. Synergistic enhancement in the cell death with HT and an additive enhancement with radiation were observed following He-CAP treatment. The synergistic effects were accompanied by increased intracellular reactive oxygen species (ROS) production. Hydrogen peroxide (H2O2) and superoxide (O2•-) generation was increased immediately after He-CAP treatment, but fails to initiate cell death process. Interestingly, at late hour's He-CAP-induced O2•- generation subsides, however the combined treatment showed sustained increased intracellular O2•- level, and enhanced cell death than either treatment alone. He-CAP caused marked induction of ROS in the aqueous medium, but He-CAP-induced ROS seems insufficient or not completely incorporated intra-cellularly to activate cell death machinery. The observed synergistic effects were due to the HT effects on membrane fluidity which facilitate the incorporation of He-CAP-induced ROS into the cells, thus results in the enhanced cancer cell death following combined treatment. These findings would be helpful when establishing a therapeutic strategy for CAP in combination with HT or radiation.

| S-EPMC5600975 | biostudies-literature

Design and assembly of ternary Pt/Re/SnO2 NPs by controlling the zeta potential of individual Pt, Re, and SnO2 NPs.

Project description:In this study Pt, Re, and SnO2 nanoparticles (NPs) were combined in a controlled manner into binary and ternary combinations for a possible application for ethanol oxidation. For this purpose, zeta potentials as a function of the pH of the individual NPs solutions were measured. In order to successfully combine the NPs into Pt/SnO2 and Re/SnO2 NPs, the solutions were mixed together at a pH guaranteeing opposite zeta potentials of the metal and oxide NPs. The individually synthesized NPs and their binary/ternary combinations were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning transmission electron microscopy (STEM) combined with energy dispersive X-ray spectroscopy (EDS) analysis. FTIR and XPS spectroscopy showed that the individually synthesized Pt and Re NPs are metallic and the Sn component was oxidized to SnO2. STEM showed that all NPs are well crystallized and the sizes of the Pt, Re, and SnO2 NPs were 2.2, 1.0, and 3.4 nm, respectively. Moreover, EDS analysis confirmed the successful formation of binary Pt/SnO2 and Re/SnO2 NP, as well as ternary Pt/Re/SnO2 NP combinations. This study shows that by controlling the zeta potential of individual metal and oxide NPs, it is possible to assemble them into binary and ternary combinations. Graphical abstract?.

| S-EPMC5949135 | biostudies-literature

Hyperthermia-triggered biomimetic bubble nanomachines.

Project description:Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor penetration of nanodrugs remains a significant hurdle for effective tumor therapy due to the existing biological barriers of tumoral microenvironment. Inspired by bubble machines, here we report the successful fabrication of biomimetic nanodevices capable of in-situ secreting cell-membrane-derived nanovesicles with smaller sizes under near infrared (NIR) laser irradiation for synergistic photothermal/photodynamic therapy. Porous Au nanocages (AuNC) are loaded with phase transitable perfluorohexane (PFO) and hemoglobin (Hb), followed by oxygen pre-saturation and indocyanine green (ICG) anchored 4T1 tumor cell membrane camouflage. Upon slight laser treatment, the loaded PFO undergoes phase transition due to surface plasmon resonance effect produced by AuNC framework, thus inducing the budding of outer cell membrane coating into small-scale nanovesicles based on the pore size of AuNC. Therefore, the hyperthermia-triggered generation of nanovesicles with smaller size, sufficient oxygen supply and anchored ICG results in enhanced tumor penetration for further self-sufficient oxygen-augmented photodynamic therapy and photothermal therapy. The as-developed biomimetic bubble nanomachines with temperature responsiveness show great promise as a potential nanoplatform for cancer treatment.

| S-EPMC10421929 | biostudies-literature

A self-supporting bimetallic Au@Pt core-shell nanoparticle electrocatalyst for the synergistic enhancement of methanol oxidation.

Project description:The morphology of Pt-Au bimetal nanostructures plays an important role in enhancing the catalytic capability, catalytic stability and utilization efficiency of the platinum. We designed and successfully prepared Au@Pt nanoparticles (NPs) through an economical, surfactant-free and efficient method of seed-mediated growth. The Au@Pt NPs displayed electrochemical performances superior to those of commercial Pt/C catalysts because their agglomeration was prevented and exhibited better long-term stability with respect to methanol oxidation in acidic media by efficiently removing intermediates. Among the obtained Au@Pt NPs, Au90@Pt10 NPs exhibited the most significantly enhanced catalytic performance for the methanol oxidation reaction (MOR). Their mass and electrochemically active surface area (ECSA)-normalized current densities are approximately 3.9 and 4.6 times higher than those of commercial Pt/C catalysts, respectively. The oxidation current densities of the Au90@Pt10 NPs are approximately 1.8 times higher than those of commercial Pt/C catalysts after 4000 s of continuous measurement because the small Pt NPs grown on the surface of the Au90@Pt10 NPs were effectively stabilized by the Au metal support. This approach may be a facile method for the synthesis of self-supported bimetallic nanostructures, which is of great significance for the development of high performance electrocatalysts and sensors.

| S-EPMC5524951 | biostudies-literature

NIR-Laser-Controlled Drug Release from DOX/IR-780-Loaded Temperature-Sensitive-Liposomes for Chemo-Photothermal Synergistic Tumor Therapy.

Project description:NIR laser-induced photothermal therapy (PTT) through near-infrared agents has demonstrated the great potential in solid tumor ablation. However, the nonuniform heat distribution over tumors from PTT makes it insufficient to kill all tumor cells, resulting in tumor recurrence and inferior outcomes. To improve the tumor treatment efficacy, it is highly desirable to develop the combinational treatment of PTT with other modalities, especially with chemotherapeutic agents. Here we report a smart DOX/IR-780-loaded temperature-sensitive-liposome (DITSL) which can achieve NIR-laser-controlled drug release for chemo-photothermal synergistic tumor therapy. In this system, the liposoluble IR-780 was incorporated into the temperature-sensitive lipid bilayer and the soluble chemotherapeutic doxorubicin (DOX) was encapsulated in the hydrophilic core. The resulting DITSL is proved to be physiologically stable and can provide a fast and laser irradiation-controllable DOX release in the PBS and cellular conditions. We further employed this nanoparticle for tumor treatment, demonstrating significantly higher tumor inhibition efficacy than that of DOX-loaded temperature-sensitive-liposome (DTSL) or IR780-loaded temperature-sensitive-liposome (ITSL) in the in vitro cells and in vivo animals. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of DITSL over DTSL or ITSL. Our study provides a promising strategy to realize chemo-photothermal synergistic combination therapy for breast tumors.

| S-EPMC5118599 | biostudies-literature

Hydrotalcite-Embedded Magnetite Nanoparticles for Hyperthermia-Triggered Chemotherapy.

Project description:A magnetic nanocomposite, consisting of Fe3O4 nanoparticles embedded into a Mg/Al layered double hydroxide (LDH) matrix, was developed for cancer multimodal therapy, based on the combination of local magnetic hyperthermia and thermally induced drug delivery. The synthesis procedure involves the sequential hydrolysis of iron salts (Fe2+, Fe3+) and Mg2+/Al3+ nitrates in a carbonate-rich mild alkaline environment followed by the loading of 5-fluorouracil, an anionic anticancer drug, in the interlayer LDH space. Magnetite nanoparticles with a diameter around 30 nm, dispersed in water, constitute the hyperthermia-active phase able to generate a specific loss of power of around 500 W/g-Fe in an alternating current (AC) magnetic field of 24 kA/m and 300 kHz as determined by AC magnetometry and calorimetric measurements. Heat transfer was found to trigger a very rapid release of drug which reached 80% of the loaded mass within 10 min exposure to the applied field. The potential of the Fe3O4/LDH nanocomposites as cancer treatment agents with minimum side-effects, owing to the exclusive presence of inorganic phases, was validated by cell internalization and toxicity assays.

| S-EPMC8308439 | biostudies-literature

Natural Killer Cell Membrane-Cloaked Virus-Mimicking Nanogenerator with NIR-Triggered Shape Reversal and •C/•OH Storm for Synergistic Thermodynamic-Chemodynamic Therapy.

Project description:Free radical-based anticancer modality has been widely applied to cancer therapies. However, it still faces challenges of low delivery efficiency and poor selectivity of free radical generation specifically toward tumors. Herein, a virus-mimicking hollow mesoporous disulfide-bridged organosilica is designed to encapsulate •C precursor 2, 2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), which is then enclosed by tannic acid (TA)/FeIII photothermal assembly and further cloaked by natural killer (NK) cell membrane to achieve synergistic thermodynamic-chemodynamic therapy. The nanogenerator can first evade immune surveillance via NK cell membrane "cloaking" mechanism to strongly accumulate in tumors. Interestingly, the NIR laser-induced heat can trigger NK cell membrane rupture for "shape reversal" to expose a virus-like surface to amplify the cellular uptake, and simultaneously break the azo bonds of AIPH for in situ controlled •C generation. Then upon glutathione (GSH) triggering, the nanogenerator disintegrates via disulfide-thiol exchange and efficiently generates •OH by lysosomal pH-initiated TA-FeIII reaction; notably, the consumption of GSH can amplify oxidative stress to enhance free radical therapy by weakening the self-defense mechanism of tumor cells. It is envisioned that the NK cell membrane-cloaked virus-mimicking and NIR/GSH sequentially activated •C/•OH radical nanogenerator can provide a promising strategy for oxidative stress-based anticancer therapy.

| S-EPMC8844581 | biostudies-literature

Hyperthermia-Triggered Doxorubicin Release from Polymer-Coated Magnetic Nanorods.

Project description:In this paper, it is proposed that polymer-coated magnetic nanorods (MNRs) can be used with the advantage of a double objective: first, to serve as magnetic hyperthermia agents, and second, to be used as magnetic vehicles for the antitumor drug doxorubicin (DOX). Two different synthetic methodologies (hydrothermal and co-precipitation) were used to obtain MNRs of maghemite and magnetite. They were coated with poly(ethyleneimine) and poly(sodium 4-styrenesulfonate), and loaded with DOX, using the Layer-by-Layer technique. Evidence of the polymer coating and the drug loading was justified by ATR-FTIR and electrophoretic mobility measurements, and the composition of the coated nanorods was obtained by a thermogravimetric analysis. The nanorods were tested as magnetic hyperthermia agents, and it was found that they provided sufficiently large heating rates to be used as adjuvant therapy against solid tumors. DOX loading and release were determined by UV-visible spectroscopy, and it was found that up to 50% of the loaded drug was released in about 5 h, although the rate of release could be regulated by simultaneous application of hyperthermia, which acts as a sort of external release-trigger. Shape control offers another physical property of the particles as candidates to interact with tumor cells, and particles that are not too elongated can easily find their way through the cell membrane.

| S-EPMC6835812 | biostudies-literature

NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer.

Project description:BackgroundOwing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy.MethodsNovel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC.ResultsThe as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency.ConclusionA noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.

| S-EPMC7923633 | biostudies-literature

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