Metal-Based Photosensitizers as Inducers of Regulated Cell Death Mechanisms

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10135 - 10155

Published: Aug. 3, 2023

Over the last few decades, various forms of regulated cell death (RCD) have been discovered and were found to improve cancer treatment. Although there are several reviews on RCD induced by photodynamic therapy (PDT), a comprehensive summary covering metal-based photosensitizers (PSs) as inducers has not yet presented. In this review, we systematically summarize works PSs that induce different types RCD, including ferroptosis, immunogenic (ICD), pyroptosis. The characteristics mechanisms each explained. At end section, reported commonalities between inducing same is emphasized, future perspectives novel discussed at review. Considering essential roles in therapy, hope review will provide stage for advances inducers.

Language: Английский

---

Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 2, 2023

Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove primary tumor, remain poorly accessible. To overcome this limitation, herein, development a theranostic nanomaterial by incorporating chromophore for imaging and photosensitizer treatment metastatic tumor sites is presented. The mechanism action reveals that nanoparticles able intervene local generation cellular damage through photodynamic therapy as well systemic induction an immune response immunotherapy upon inhibition mTOR signaling pathway which crucial importance onset, progression spreading. strongly reduce volume eradicates in breast cancer multi-drug resistant patient-derived hepatocellular carcinoma models female mice.

Language: Английский

---

Riding the metal wave: A review of the latest developments in metal-based anticancer agents

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 501, P. 215579 - 215579

Published: Nov. 28, 2023

Language: Английский

---

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8991 - 9003

Published: March 21, 2024

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as first example Ru(II) supramolecular ICD inducer. synergistically potentiates immunomodulatory and reduces adverse through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting tumor cells, precision organelle localization, improved penetration/retention capabilities. Specifically, demonstrates excellent depth-activated ROS production (∼1 cm), resistance to diffusion, anti-ROS quenching. Moreover, exhibits promising results cellular uptake generation cancer cells multicellular spheroids. Importantly, induces more efficient an ultralow dose (10 μM) compared conventional agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency inducer, eliciting CD8+ T depleting Foxp3+ effects. Our research lays foundation for design secure exceptionally potent metal-based agents immunotherapy.

Language: Английский

---

Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

---

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10217 - 10233

Published: April 2, 2024

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors still suboptimal or even noneffective presently. Compared to cancers, exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress activity immune cells, (2) pro-tumorigenic domestication cells microenvironment within further undermines effectiveness immunotherapy, (3) dense physical barrier tumor tissues prevents intratumoral infiltration contact killing active cells. Therefore, we believe that reversing are critical priority for tumors. Due unique morphologies, structures, compositions, nanomedicines have become powerful tools achieving this goal. In Perspective, will first briefly introduce then summarize most recent progresses nanomedicine-based by remodeling immune-microenvironment a comprehensive manner. It highly expected Perspective aid advancing tumors, optimistic on future development burgeoning field.

Language: Английский

---

Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Language: Английский

---

Copper and Copper Complexes in Tumor Therapy

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(11)

Published: March 6, 2024

Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential maintaining homeostasis, as imbalances can lead to toxicity cell death. development drugs that target homeostasis emerged promising strategy anticancer treatment, with particular focus on chelators, ionophores, novel complexes. Recent research also investigated the complexes therapy.

Language: Английский

---

Development of tumor-evolution-targeted anticancer therapeutic nanomedicineEVT

Chem, Journal Year: 2024, Volume and Issue: 10(5), P. 1337 - 1356

Published: Jan. 25, 2024

Language: Английский

---

Endoplasmic Reticulum‐Targeting Iridium(III) Nanosonosensitizer Amplifies Immunogenic Cell Death for Boosted Tumor Sono‐Immunotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(26)

Published: Feb. 27, 2024

Abstract Reactive oxygen species (ROS)‐induced endoplasmic reticulum (ER) stress in sonodynamic therapy (SDT) can elicit immunogenic cell death (ICD)‐initiated antitumor immunity for augmented sono‐immunotherapy. However, unsatisfactory activity and mediocre ER induction ability of sonosensitizers essentially restrict SDT efficacy ICD stimulation. Herein, a versatile ER‐targeting Iridium(III) nanosonosensitizer is developed as superior inducer boosted tumor An ingenious cholic acid (CA)‐functionalized sonosensitizer Ir‐CA well‐designed skillfully crosslinked with human serum albumin (HSA) to form HSA@Ir‐CA. With high stability, favorable tumor‐targeting ability, reduction‐responsiveness, HSA@Ir‐CA preferentially accumulates sites enhanced cellular uptake, followed by rapid disassembly responding intracellular reductive environment. The uncaged selectively accumulate precisely disrupt situ produced type I II ROS upon US irradiation high‐efficiency SDT. Moreover, the maximized eminently amplifies evoke robust systemic immunity, inhibiting growths primary/distant tumor, lung metastasis, recurrence. This combined immune checkpoint inhibitor (αPD‐L1) further achieves reinforced therapeutic outcome against immunologically “cold” tumor. study presents an effective paradigm optimize amplify ICD‐initiated responses

Language: Английский

---