Dual-Enzyme-Instructed Peptide Self-Assembly to Boost Immunogenic Cell Death by Coordinating Intracellular Calcium Overload and Chemotherapy DOI
H. H. Zhang, Yuhan Hu,

Yinghao Ding

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: 19(1), P. 488 - 503

Published: Jan. 4, 2025

The concept of immunogenic cell death (ICD) induced by chemotherapy as a potential synergistic modality for cancer immunotherapy has been widely discussed. Unfortunately, most chemotherapeutic agents failed to dictate effective ICD responses due their defects in inducing potent signaling. Here, we report dual-enzyme-instructed peptide self-assembly platform CPMC (CPT-GFFpY-PLGVRK-Caps) that cooperatively utilizes camptothecin (CPT) and capsaicin (Caps) promote engage systemic adaptive immunity tumor rejection. Although CPT Caps respectively prevent progression inhibiting type-I DNA topoisomerase activating transient receptor cation channel subfamily V member 1 (TRPV1) intracellular calcium overload, neither alone effectively stimulates sufficient signaling meet immunotherapeutic needs. CPMC, sequentially allowing an active derivative VRK-Caps release extracellularly intracellularly, can synergize two distinct apoptosis pathways stimulated increase immunogenicity elicit T-cell-based immunity. Consequently, facilitates the generation improved tumor-specific cytotoxic T-cell sustained immunological memory, successfully suppressing both primary distant tumors. Moreover, render tumors susceptible PD-L1 blockade with antiprogrammed death-ligand (aPDL1) antibody inhibition. Combining drugs low ICD-stimulating capacity using strategy was demonstrated boost potentiate immunotherapy.

Language: Английский

An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer DOI
Lili Wang,

Ruilin Guan,

Lina Xie

et al.

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(9), P. 4657 - 4665

Published: Nov. 21, 2020

Immunogenic cell death (ICD) is a vital component of therapeutically induced anti-tumor immunity. An iridium(III) complex (Ir1), containing an N,N-bis(2-chloroethyl)-azane derivate, as endoplasmic reticulum-localized ICD inducer for non-small lung cancer (NSCLC) reported. The characteristic discharge damage-associated molecular patterns (DAMPs), that is, surface exposure calreticulin (CRT), extracellular exclusion high mobility group box 1 (HMGB1), and ATP, were generated by Ir1 in A549 cells, accompanied increase reticulum stress reactive oxygen species (ROS). vaccination immunocompetent mice with Ir1-treated dying cells elicited antitumor CD8+ T response Foxp3+ depletion, which eventually resulted long-acting immunity the activation cells. first Ir-based capable developing immunomodulatory immunogenic death.

Language: Английский

Citations

209
Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition) DOI Creative Commons
Jian Zhou, Hui‐Chuan Sun, Zheng Wang

et al.

Liver Cancer, Journal Year: 2023, Volume and Issue: 12(5), P. 405 - 444

Published: Jan. 1, 2023

Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, the fourth most common malignancy and second leading cause tumor-related death, thereby posing a significant threat to life health Chinese people.Since publication Guidelines for Diagnosis Treatment Liver Cancer China June 2017, were updated by National Health Commission December 2019, additional high-quality evidence has emerged from researchers worldwide regarding diagnosis, staging, treatment that requires guidelines be again. The new edition (2022 Edition) was written more than 100 experts field cancer not only reflects real-world situation but also may reshape nationwide diagnosis cancer.The guideline aims encourage implementation evidence-based practice improve national average 5-year survival rate patients with as proposed "Health 2030 Blueprint."

Language: Английский

Citations

200
A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer DOI Creative Commons
Dandan Sun, Yifang Zou, Song Liu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(1), P. 378 - 393

Published: June 18, 2021

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety cancers, efficacy inhibitors is still low in colorectal (CRC). This mainly due to immunosuppressive feature tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating potential remodeling TME. In this study, ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using

Language: Английский

Citations

127
Anti-inflammatory and immunoregulatory effects of icariin and icaritin DOI Open Access
Zhangyang Bi, Wei Zhang, Xiaoyan Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 151, P. 113180 - 113180

Published: May 27, 2022

Inflammation and immunity dysregulation have received widespread attention in recent years due to their occurrence the pathophysiology of many conditions. In this regard, several pharmacological studies been conducted aiming evaluate potential anti-inflammatory immunomodulatory effects phytochemicals. Epimedium, a traditional Chinese medicine, is often used as tonic, aphrodisiac, anti-rheumatic agent. Icariin (ICA) main active ingredient Epimedium is, once ingested, mainly metabolized into Icaritin (ICT). Data from vitro vivo suggested that ICA its metabolite (ICT) regulated functions activation immune cells, modulated release inflammatory factors, restored aberrant signaling pathways. ICT were also involved responses diseases, including multiple sclerosis, asthma, atherosclerosis, lupus nephritis, bowel rheumatoid arthritis, cancer. Yet, data showed exhibited similar but not identical pharmacokinetic properties. Therefore, based on higher solubility bioavailability, well trends indicating single-ingredient compounds offer broader safer therapeutic capabilities, delivery systems treatment represent interesting avenues with promising clinical applications. study, we reviewed mechanisms, properties ICT.

Language: Английский

Citations

127
Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy DOI
Wei Jiang,

Wang Dong,

Min Li

et al.

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 3881 - 3894

Published: March 3, 2022

Tumor cells undergoing immunogenic cell death (ICD) release damage-associated molecular patterns (DAMPs) to trigger a long-term protective antitumor response. ICD can be induced by certain pathogens, chemotherapeutics, and physical modalities. In this work, we demonstrate that gaseous molecule, specifically nitric oxide (NO), induce potent effect. NO exerts cytotoxic effects are accompanied the emission of DAMPs based on endoplasmic reticulum stress mitochondrial dysfunction pathways. Released elicit immunological protection against subsequent rechallenge syngeneic tumor in immunocompetent mice. We prepare polynitrosated polyesters with high storage capacity through facile polycondensation reaction followed postsynthetic modification. The polyesters-based nanogenerator (NanoNO) enables efficient delivery controlled tumors induces sufficient different immune-intact models tumors, NanoNO exhibits significant growth suppression increases local dose signals T infiltrations, ultimately prolonging survival. addition, synergizes PD-1 blockade prevent metastasis. conclude not only is inducer for cancer immunotherapy but also it expands range inducers into field molecules.

Language: Английский

Citations

126
Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma DOI Creative Commons
Jianfeng Guo, Zhuo Yu, Dandan Sun

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 6, 2021

Abstract Background FOLFOX is a combinational regimen of folinic acid (FnA, FOL ), fluorouracil (5-Fu, F ) and oxaliplatin (OxP, OX has been long considered as the standard treatment colorectal cancer (CRC) hepatocellular carcinoma (HCC). Recent developments nano delivery systems have provided profound promise for improving anticancer efficacy alleviating side effects FOLFOX. Previously, nanoformulation (termed Nano-Folox) containing OxP derivative FnA was developed in our laboratory using nanoprecipitation technique. Nano-Folox induced OxP-mediated immunogenic cell death (ICD)-associated antitumor immunity, which significantly suppressed tumor growth orthotopic CRC mouse model when administrated combination with free 5-Fu. Methods A Nano-FdUMP) FdUMP (5-Fu active metabolite) newly technique used HCC therapies. Results Synergistic achieved models. It resulted mainly from fact that Nano-FdUMP mediated formation reactive oxygen species (ROS), promoted ICD elicited by Nano-Folox. In addition, Nano-Folox/Nano-FdUMP anti-PD-L1 antibody inhibited liver metastasis, leading to long-term survival mice. Conclusion This study provides proof concept two can result successful FOLFOX-associated Further optimization terms dosing timing will enhance clinical potential this strategy patients. Graphical abstract

Language: Английский

Citations

116
d -lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma DOI Creative Commons
Shulan Han, Xueying Bao, Yifang Zou

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(29)

Published: July 19, 2023

The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) hepatocellular carcinoma (HCC). d-lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells clearance pathogens. In this study, DL transformation TAMs was confirmed, and mechanisms underlying such were mainly due modulation phosphatidylinositol 3-kinase/protein kinase B pathway. A poly(lactide-co-glycolide) nanoparticle (NP) used load DL, DL-loaded NP modified with HCC membrane macrophage-binding peptide (M2pep), forming nanoformulation (DL@NP-M-M2pep). DL@NP-M-M2pep transformed remodeled TME in mice, promoting efficacy anti-CD47 antibody long-term animal survival. These findings reveal TAM modulatory function provide combinatorial strategy immunotherapy.

Language: Английский

Citations

110
Drug-induced oxidative stress in cancer treatments: Angel or devil? DOI Creative Commons
Hao Jiang, Jing Zuo, Bowen Li

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102754 - 102754

Published: May 18, 2023

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one the most significant biological events cancer progression. Cancer cells generally represent a higher level, which suggests dual therapeutic strategy by regulating status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, exhibits great anti-cancer capability, attributing to accumulation within cells, whereas restore homeostasis has been claimed fail several clinical practices. Targeting vulnerability pro-oxidants capable generating excessive reactive oxygen species (ROS) surfaced an important strategy. However, multiple adverse effects caused indiscriminate attacks uncontrolled drug-induced OS on normal tissues and drug-tolerant capacity some certain greatly limit their further applications. Herein, we review representative oxidative drugs summarize side organs, emphasizing that seeking balance between damage value exploiting next-generation OS-based chemotherapeutics.

Language: Английский

Citations

102
Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology DOI Creative Commons
Yi Lu,

Qiulan Luo,

Xiaobin Jia

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2022, Volume and Issue: 13(3), P. 239 - 254

Published: Dec. 30, 2022

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium (EF) possess excellent therapeutic effects on various diseases. Encouragingly, 2022, soft capsules were approved to reach market for treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) China. Moreover, recent studies demonstrate that can serve immune-modulating agent exert anti-tumor effects. Nonetheless, both production efficiency clinical applications epimedium flavonoids have been restrained because their low content, poor bioavailability, unfavorable vivo delivery efficiency. Recently, strategies, including enzyme engineering nanotechnology, developed increase productivity activity, improve efficiency, enhance flavonoids. In this review, structure-activity relationship is described. Then, enzymatic strategies increasing highly discussed. The nanomedicines overcoming barriers improving diseases summarized. Finally, challenges an outlook translation proposed.

Language: Английский

Citations

100
Intravenous Delivery of Living Listeria monocytogenes Elicits Gasdmermin-Dependent Tumor Pyroptosis and Motivates Anti-Tumor Immune Response DOI
Yao Liu, Yiping Lu, Bo Ning

et al.

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 4102 - 4115

Published: March 9, 2022

The facultative intracellular bacterium Listeria monocytogenes (Lmo) has great potential for development as a cancer vaccine platform given its properties. However, the clinical application of Lmo been severely restricted due to rapid clearance, compromised immune response in tumors, and inevitable side effects such severe systemic inflammation after intravenous administration. Herein, an immunotherapy system was developed on basis natural red blood cell (RBC) membranes encapsulated with selective deletion virulence factors (Lmo@RBC). biomimetic Lmo@RBC not only generated low inflammatory but also enhanced accumulation tumors long circulation tumor hypoxic microenvironment favoring anaerobic colonization. After genome screening treated PBS, Lmo, or Lmo@RBC, it first found that induced extensive pore-forming protein gasdermin C (GSDMC)-dependent pyroptosis, which reversed immunosuppressive promoted strong durable anti-tumor response, resulting excellent therapeutic effect solid metastasis. Overall, living bacterial therapy initiation pyrolysis, provided proof-of-concept live bacteria potentiating therapy.

Language: Английский

Citations

94