Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

Advanced Science, Journal Year: 2022, Volume and Issue: 9(22)

Published: June 2, 2022

Abstract Tumor immunotherapy is only effective in a fraction of patients due to low response rate and severe side effects, these challenges clinics can be addressed through induction immunogenic cell death (ICD). ICD elicited from many antitumor therapies release danger associated molecular patterns (DAMPs) tumor‐associated antigens facilitate maturation dendritic cells (DCs) infiltration cytotoxic T lymphocytes (CTLs). The process reverse the tumor immunosuppressive microenvironment improve sensitivity immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored induce by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) photodynamic therapy (PDT), photothermal conversion agents (PTT), radiosensitizers radiotherapy (RT). These NDDSs loaded at right dose place time, resulting greater effectiveness lower toxicity. Immunotherapeutic also combined with achieve synergic effect multi‐modality approach. In this review, harnessed load multiple PDT, PTT, RT combination promote reduce effects cancer treatment.

Language: Английский

---

Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation

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

Published: May 23, 2023

The immunologically "cold" microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property gas therapy with cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway activation augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation AIEgen and manganese carbonyl fabricate nanoadjuvant. As tetra-sulfide bonds are responsive intratumoral glutathione, nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, AIEgen-mediated phototherapy triggers burst carbon monoxide (CO)/Mn2+. Both H2S CO can destroy mitochondrial integrity induce leakage DNA into cytoplasm, serving as immunoadjuvants activate cGAS-STING pathway. Meanwhile, Mn2+ sensitize cGAS STING-mediated type I production. Consequently, potentiates photoimmunotherapy poorly immunogenic tumors female mice.

Language: Английский

---

Theranostic Fluorescent Probes

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2699 - 2804

Published: Feb. 29, 2024

The ability to gain spatiotemporal information, and in some cases achieve control, the context of drug delivery makes theranostic fluorescent probes an attractive intensely investigated research topic. This interest is reflected steep rise publications on topic that have appeared over past decade. Theranostic probes, their various incarnations, generally comprise a fluorophore linked masked drug, which released as result certain stimuli, with both intrinsic extrinsic stimuli being reported. release then signaled by emergence signal. Importantly, use appropriate fluorophores has enabled not only this emerging fluorescence marker for but also provided modalities useful photodynamic, photothermal, sonodynamic therapeutic applications. In review we highlight recent work particular focus are activated tumor microenvironments. We summarize efforts develop other applications, such neurodegenerative diseases antibacterials. celebrates diversity designs reported date, from discrete small-molecule systems nanomaterials. Our aim provide insights into potential clinical impact still-emerging direction.

Language: Английский

---

Quasi-LD-Targeted and ONOO^–-Responsive Fluorescent Probe for Investigating the Interaction of Nonalcoholic Fatty Liver with Drug-Induced Liver Injury

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(14), P. 5967 - 5975

Published: March 29, 2023

Hepatic lipid droplets (LDs) and peroxynitrite (ONOO-) levels are closely related to nonalcoholic fatty liver disease (NAFLD). Additionally, some drug-induced injury (DILI) is often associated with ONOO-. Here, we constructed screened the quasi-LDs-targeted ONOO--responsive fluorescent probe MBDP-Py+ investigate interaction of NAFLD DILI. By monitoring upregulation ONOO- accumulation LDs, was more sensitive efficient than tissue staining serum markers detection in evaluating early toxicity diagnosing anticancer-DILI. More importantly, enhancement fluorescence signals demonstrated that different stages NAFLD, dominant element combined DILI mice models. As degree deepens, synergistic effect two will lead serious damage.

Language: Английский

---

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(8)

Published: Jan. 22, 2022

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging photoactivated treatment are limited. Therefore, new II (NIR-II) molecule (named TST), which had abilities aggregation-induced emission (AIE) photothermal therapy synthesized. Moreover, order further improve its yield therapeutic effect, camptothecin prodrug (CPT-S-PEG) novel immune checkpoint inhibitor AZD4635 used co-assemble with TST into nanoparticles for drug delivery. On account strong interaction TST, intramolecular rotation is limited, thereby inhibiting non-radiation attenuation promoting fluorescence generation when intact. As uptake by cancer cells, redox sensitive CPT-S-PEG degraded disintegrate. The released enhances non-radiative expedites conversion because removal constraint camptothecin. Furthermore, induces immunogenic cell death cells releases abundant ATP tumor microenvironment recruit cells. However, superfluous converted immunosuppressive adenosine through CD39-CD73-A2AR pathway. disintegration just blocks this pathway timely, achieving favorable synergistic therapy, chemotherapy, immunotherapy.

Language: Английский

---

Carrier-Free Immunotherapeutic Nano-Booster with Dual Synergistic Effects Based on Glutaminase Inhibition Combined with Photodynamic Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(2), P. 1583 - 1596

Published: Jan. 3, 2023

The immunotherapeutic effect elicited by photodynamic therapy (PDT) is attenuated tumor defense mechanisms associated with glutamine metabolism, including the metabolic regulation of redox homeostasis and limitation immunosuppressive microenvironment (ITM). Herein, a carrier-free nanobooster C9SN dual synergistic effects was constructed self-assembly glutaminase (GLS) inhibitor compound 968 (C968) photosensitizer Chlorin e6. C968-mediated GSH deprivation through inhibiting metabolism prevented PDT-generated reactive oxygen species from being annihilated GSH, amplifying intracellular oxidative stress, which caused severe cell death also enhanced immunogenic (ICD) effect. In addition, genome-wide analysis carried out using RNA-sequencing to evaluate changes in transcriptome induced stress. Thereafter, neoantigens generated ICD promoted maturation dendritic cells, thereby recruiting activating cytotoxic T lymphocytes (CTLs). Meanwhile, remodeled ITM blocking polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, further recruited activated CTLs. Ultimately, this suppressed primary distant tumors. This "kill two birds one stone" strategy would shed light on enhancing immunogenicity alleviating immunosuppression improve PDT.

Language: Английский

---

Recent advances in fluorescence imaging-guided photothermal therapy and photodynamic therapy for cancer: From near-infrared-I to near-infrared-II

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 362, P. 425 - 445

Published: Sept. 8, 2023

Language: Английский

---

Recent advances in the design and applications of near-infrared II responsive small molecule phototherapeutic agents

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 505, P. 215677 - 215677

Published: Jan. 31, 2024

Language: Английский

---

Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics

ACS Nano, Journal Year: 2024, Volume and Issue: 18(6), P. 4683 - 4703

Published: Jan. 31, 2024

Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), high electron affinity, is widely utilized as acceptor constructing donor–acceptor–donor (D-A-D) structured fluorophores intensive (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based dyes been employed tumor phototheranostics due to their exceptional structure tunability, biocompatibility, photophysical properties. This review systematically overviews research progress of small molecular focuses on molecule design bioapplications. First, engineering strategies fine-tune properties high-performance are discussed detail. Then, applications optical imaging phototherapy highlighted. Finally, current challenges future prospects also summarized. believed significantly promote further BBT-derived for

Language: Английский

---

Recent advances in NIR-II fluorescence/photoacoustic dual-modality imaging probes

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 514, P. 215907 - 215907

Published: May 12, 2024

Language: Английский

---