Photothermal therapy with immune nanoparticles

BACKGROUND: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. METHODS: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex , termed UPS)...

The significant regulatory role of palmitoylation modification in cancer-related targets has been demonstrated previously. However, the biological functions of Nrf2 in stomach cancer and whether the presence of Nrf2 palmitoylation affects gastric cancer (GC) progression and its treatment have not been reported. Several public datasets were used to look into the possible link between the amount of palmitoylated Nrf2 and the progression and its outcome of GC in patients. The palmitoylated Nrf2 levels in tumoral and peritumoral tissues from GC patients were also evaluated...

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating...

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here we propose a remotely unwrapping strategy of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH could be triggered by the intravenously injected DFO, resulting in the release, reactivation and deep penetration of encapsulated HAase inside tumors...

Hepatocellular carcinoma (HCC) is an immunosuppressive tumor associated with high mortality. Photothermal and photodynamic therapies have been applied to induce immunogenic cell death (ICD) in HCC, successfully eliciting immune responses but facing limitations in penetration depth in clinical trials. Here, intrinsic mitochondrial hyperthermia was used to trigger thermosensitive drug release. The mitochondria were further self-heated through 2,4-dinitrophenol uncoupling, dramatically promoting free radical initiation and inducing tumor ICD...

INTRODUCTION: Responsive drug delivery systems hold great promise for tumor treatment as they focus on therapeutic agents directly, thus minimizing systemic toxicities and drug leakage. In this study, we covalently bound a matrix metalloproteinases-2 (MMP-2) enzyme-sensitive peptide to a tissue-penetrating peptide to rationally design a MMP-2 responsive multifunctional peptide hydrogel platform (aP/IR@FMKB) for cancer photothermal-chemo-immunotherapy. The constructed aP/IR@FMKB with bufalin (BF) loaded in trimethyl chitosan nanoparticles (TB NPs), photothermal agent IR820, and immune checkpoint inhibitor aPD-L1 by self-assembly could be dissociated in the presence of MMP-2 enzyme, triggering content release...

Current antibacterial interventions encounter formidable challenges when confronting intracellular bacteria, attributable to their clustering within phagocytes, particularly macrophages, evading host immunity and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem, denoted as MM@DAu NPs, which seamlessly integrates cascade-targeting capabilities with controllable antibacterial functions for the precise elimination of intracellular bacteria. MM@DAu NPs feature a core comprising D-alanine-functionalized gold nanoparticles (DAu NPs) enveloped by a macrophage cell membrane (MM) coating...

Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection...

Metabolic heterogeneity and the tumor immunosuppressive microenvironment (TIME) of triple-negative breast cancer (TNBC) hinder therapeutic effectiveness. Although emerging metabolic therapy and immunotherapy show promise, they are limited by off-target effects and immune escape. Here, a redox-activatable, sequentially-releasing nanoparticle (AMANC@M) for tumor-targeted delivery of anticancer agents and CRISPR/Cas9 has been developed. AMANC@M can reverse the TIME through dual metabolic inhibition, thereby enhancing TNBC therapy...

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS2 , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC...

Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264...

Recent advances in adoptive T-cell therapy have delivered impressive therapeutic outcomes by instigating enduring anti-tumor responses. Nonetheless, achieving specific T-cell activation remains a challenge due to several factors. Some cancer cells evade T-cell recognition due to the scarcity of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) presentation. Notably underestimated is the impact of waning T-cell receptor (TCR) expression and the constrained formation of immune synapses (IS) between dendritic cells (DCs) and T cells, impairing T-cell activation...

The key properties and high versatility of metal nanoparticles have shed new perspectives on cancer therapy, with copper nanoparticles gaining great interest because of the ability to couple the intrinsic properties of metal nanoparticles with the biological activities of copper ions in cancer cells. Copper, indeed, is a cofactor involved in different metabolic pathways of many physiological and pathological processes. Literature data report on the use of copper in preclinical protocols for cancer treatment based on chemo-, photothermal-, or copper chelating-therapies...

Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns...

Massive efforts have been concentrated on the advance of eminent near-infrared (NIR) photothermal materials (PTMs) in the NIR-II window (1000-1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-II-responsive organic PTMs was explored, and their photothermal conversion efficiencies (PCEs) still remain relatively low. Herein, donor-acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-II window...

Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively...

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as PCM Pt/GOx) were prepared as the mild-temperature triggered pyroptosis inducer...

As one of the most common malignancies, oral squamous cell carcinoma (OSCC) with high rates of invasiveness and metastasis threatens people's health worldwide, while traditional therapeutic approaches have not met the requirement of its cure. Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have shown great potential for OSCC treatment due to their noninvasiveness or minimal invasiveness, high selectivity and little tolerance. However, PTT or PDT alone makes it difficult to eradicate OSCC and prevent its metastasis and recurrence...

Nanoparticle-based drug delivery systems have found extensive use in delivering oncology therapeutics; however, some delivery vehicles still exhibit rapid immune clearance, lack of biocompatibility, and insufficient targeting. In recent years, bionanoparticles constructed from tumour cell membranes have gained momentum as tumour-targeting therapeutic agents. Cancer cell membrane-coated nanoparticles (CCMCNPs) typically consist of a drug-loaded nanoparticle core coated with cancer cell membrane. CCMCNPs retain homologous tumour cell surface antigens, receptors, and proteins, and it has been shown that the modified nanoparticles exhibit better homologous targeting, immune escape, and biocompatibility...

INTRODUCTION: Immune checkpoint blockade (ICB) has revolutionized the therapy landscape of malignancy melanoma. However, the clinical benefits from this regimen remain limited, especially in tumors lacking infiltrated T cells (known as "cold" tumors). Nanoparticle-mediated photothermal therapy (PTT) has demonstrated improved outcomes in the ablation of solid tumors by inducing immunogenic cell death (ICD) and reshaping the tumor immune microenvironment. Therefore, the combination of PTT and ICB is a promising regimen for patients with "cold" tumors...