Modular Design and Scaffold-Synthesis of Multi-Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis DOI Creative Commons
Yuanyuan Li, Chunhui Wang, Haiyang Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 27, 2024

Abstract Modified commercial fluorophores are essential tools for optical imaging and biomedical research. Their synthetic modification to incorporate new functions, however, remains a challenging task. Conventional strategies rely on linear synthesis in which parent framework is gradually extended. We here designed synthesized versatile library of functional via scaffold-based Ugi four-component reaction (U-4CR). The adaptability the scaffold achieved through starting materials. This allows use small range materials creation fluorogenic probes that can detect reactive-oxygen species where localization into subcellular organelles or membranes be controlled. present yields ranging from 60% 90% discovered some compounds even function as therapeutic agents Fenton chemistry inducing pyroptosis living cancer cells. Our study underlines potential their applications.

Language: Английский

Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy DOI
Guo‐Qing Zhu, Yulin Xie, Junrong Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(45)

Published: Sept. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Language: Английский

Citations

15
Phototherapy: progress, challenges, and opportunities DOI
Xi Yuan,

Junliang Zhou,

Lin Yuan

et al.

Science China Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Language: Английский

Citations

10
Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma DOI
Ying Peng,

Rufan Mo,

Mingwang Yang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

The development of a photosensitizer (PS) that induces pyroptosis could be star for photodynamic therapy (PDT), particularly with type-I PSs produce reactive oxygen species (ROS) in hypoxic tumor microenvironment. Since is recently characterized cell death pathway, it holds promise advancing PDT oncology, playing critical role. Herein, we develop PS named Th-M aggregation-induced emission (AIE) characteristics against tongue squamous carcinoma (TSCC). stands out its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 Gasdermin E (GSDME) cleavage under white light irradiation, inducing TSCC cells. Our studies verify the effectiveness destroying cancer cells vitro suppressing growth vivo while also demonstrating favorable biosafety profile. This work pioneers application as mitochondria-targeted, leverages mechanism pyroptosis, offering potent approach treatment TSSC promising implications future cancers.

Language: Английский

Citations

8
Targeting Sub-Cellular Organelles for Boosting Precision Photodynamic Therapy DOI
G. Attar,

M. Kumar,

Vandana Bhalla

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Among various cancer treatment methods, photodynamic therapy has received significant attention due to its non-invasiveness and high efficiency in inhibiting tumour growth. Recently, specific organelle targeting photosensitizers have increasing interest their precise accumulation ability trigger organelle-mediated cell death signalling pathways, which greatly reduces the drug dosage, minimizes toxicity, avoids multidrug resistance, prevents recurrence. In this review, recent advances representative used targeted on organelles, specifically including endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, lysosomes, been comprehensively reviewed with a focus structure pathways. Furthermore, perspective future research potential challenges precision presented at end.

Language: Английский

Citations

4
Endoplasmic Reticulum Targeting Nanoparticle for Efficient Anti-Tumor Immunotherapy DOI

Le Sun,

Guangzhao Xu, Fahui Li

et al.

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Despite significant clinical breakthroughs in anti-tumor immunotherapy, its therapy efficiency remains hindered by insufficient "cold" tumor immune responses. The ample reactive oxygen species photodynamic (PDT) can trigger the immunogenic cell death (ICD) pathway for arousing system and realizing immunotherapy. But inherent hypoxic microenvironment (TME) limits PDT efficacy. To simultaneously reverse TME promote ICD pathway, multi-in-one nanostructure (FAIC) is designed, which catalase (CAT) photosensitizer (I-Cy5) are encapsulated a folate receptor-targeting liposome. Due to endoplasmic reticulum (ER)-targeting ability of I-Cy5, H2O2 decomposition catalytic CAT, cell-targeting liposome, severe ER stress triggered nano FAIC pathway. As result, infiltration cytotoxic T lymphocytes promoted, response boosted. design corresponding mechanism provide potential way realize efficient

Language: Английский

Citations

0
Mitochondria-targeted H2O2 homeostatic disruptors: Harnessing glutathione autoxidation and reversing GSDME “silencing” for ferroptotic and dual-pathway pyroptotic oncotherapy DOI
Junrong Wang, Yulin Xie, Guo‐Qing Zhu

et al.

Nano Today, Journal Year: 2025, Volume and Issue: 61, P. 102640 - 102640

Published: Jan. 14, 2025

Language: Английский

Citations

0
Creating Single Atomic Coordination for Hypoxia‐Resistant Pyroptosis Nano‐Inducer to Boost Anti‐Tumor Immunotherapy DOI Open Access
Wenshuai Li, Hongyuan Li, Guangwei Jiang

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract General synthesis and mechanical understanding of type I nano‐photosensitizers are great importance for hypoxia‐resistant pyroptosis inducers. Herein, a simple solvothermal treatment is developed to convert non‐photosensitive small molecules (hemin) into uniform carbon nanodots (HNCDs) with strong photodynamic activity red fluorescence emission. These HNCDs inherit the single atomic Fe–N 4 center hemin while creating sp 2 ‐hybridized surroundings, which synergistically modulated energy level electron transfer converting II process I. After encapsulating bovine serum albumin (BSA) facilitate in vivo applications, resulting BSA nanoparticles (HB) can image tumors significantly induce tumor cells even under an extremely hypoxic environment (2% O ). This evokes antitumor immune response, effectively restraining growth lung metastasis triple‐negative breast cancer mice, good biocompatibility. work introduces applicable nano‐inducer combat highlights regulation centers develop treatment.

Language: Английский

Citations

0
An ER Stress and Mitochondrial Apoptosis Co-inducer for Enhanced Cancer Immunotherapy DOI
Guangzhao Xu, Shuzhen Chen,

Hekai Yang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217485 - 217485

Published: Jan. 1, 2025

Language: Английский

Citations

0
Photo-generating Type-I ROS and aryl radicals by mitochondrial-targeting oxime-ester photogenerator for pyroptosis-mediated anti-hypoxia photoimmunotherapy DOI

Qimin Zhan,

Yu‐Lin Kuang, Xuyuan Chen

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 47, P. 327 - 342

Published: Feb. 12, 2025

Language: Английский

Citations

0
Activator Strand Modifications in CRISPR/Cas12a: Unlocking the Potential for Casp-3-Targeted Biosensing and Imaging Analysis of Apoptosis DOI

Qingnan Li,

Yunxi Cui, Zhi‐Qi Dai

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

The CRISPR/Cas12a system has emerged as a powerful tool in biosensing due to its unique trans-cleavage activity. This study conducted an in-depth investigation of the modulatory capabilities this system, particularly focusing on 5'-end modifications activator strand, and found that introducing hairpin structure (HP) at which was designed based RESET effect, can effectively suppress strand's ability activate activity system. suppression is independent HP's relation strand type linker used (DNA, RNA or peptide). Detaching HP from restores system's These findings enrich development CRISPR/Cas12a-based biosensors, expand their application beyond DNA-based target detection peptide sequence-based recognition. Based discovery, we constructed sensitive biosensor for caspase-3 (Casp-3), key executor apoptosis, by linking with containing Casp-3 recognition site. proposed been validated sensitivity specificity detecting Casp-3, well monitoring drug-induced apoptosis through imaging living cells, providing valuable studying apoptotic process, screening drugs, assessing drug efficacy, evaluating treatment outcomes. strategy also shows promise other peptide-based targets, broadening horizons early disease biomarker timely therapeutic interventions.

Language: Английский

Citations

0