Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
42
result(s) for
"Chang, Li-Chan"
Sort by:
Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments
Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H
2
O
2
→ ‧OH for tumoral therapy. Unfortunately, H
2
O
2
is often taken from the limited endogenous supply of H
2
O
2
in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H
2
O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe
3+
-N ≡ C-Fe
2+
composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O
2
, H
2
O
2,
and ‧OH from H
2
O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.
Chemodynamic therapy (CDT) uses Fenton chemistry to covert hydrogen peroxide in cancer cells to toxic hydroxyl radicals, but endogenous hydrogen peroxide is insufficient to drive sustainable CDT. Here, the authors report a water oxidation CoFe Prussian blue nanoframe to provide sustained, external energy free self-supply of hydroxyl radicals for CDT.
Journal Article
Atomically dispersed golds on degradable zero-valent copper nanocubes augment oxygen driven Fenton-like reaction for effective orthotopic tumor therapy
Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl
4
allows for the fabrication of different atomic ratios of Au
x
Cu
y
. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au
0.02
Cu
0.98
composition reveals the enhanced •OH generation following O
2
→ H
2
O
2
→ •OH. The degradable Au
0.02
Cu
0.98
released Cu
+
and Cu
2+
resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au
0.02
Cu
0.98
for O
2
→ H
2
O
2
→ •OH as well. Instead of using endogenous H
2
O
2
, H
2
O
2
can be sourced from the O
2
in the air through the use of nanocubes. Notably, the Au
0.02
Cu
0.98
structure is degradable and renal-clearable.
Single-atom catalysts emerge as nanocatalytic medicine in chemodynamic therapy but suffer from inefficient kinetics for the production of reactive oxygen species because of the cell’s antioxidative mechanisms. Here, the authors employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatment.
Journal Article
Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
Cancer remains a global health challenge necessitating innovative therapies. We introduce a strategy to disrupt cancer cell redox balance using gold nanoparticles (Au NPs) as electron sinks combined with electroactive membranes. Utilizing
Shewanella oneidensis
MR-1 membrane proteins, we develop liposomes enriched with
c
-type cytochromes. These, coupled with Au NPs, facilitate autonomous electron transfer from cancer cells, disrupting redox processes and inducing cell death. Effective across various cancer types, larger Au NPs show enhanced efficacy, especially under hypoxic conditions. Oxidative stress from Au@MIL (MIL: membrane-integrated liposome) treatments, including mitochondrial and endoplasmic reticulum lipid oxidation and mitochondrial membrane potential changes, triggers apoptosis, bypassing iron-mediated pathways. Surface plasmon band and X-ray absorption near-edge structure (XANES) analyses confirm electron transfer. A SiO
2
insulator coating on Au NPs blocks this transfer, suppressing cancer cell damage. This approach highlights the potential of modulated electron transfer pathways in targeted cancer therapy, offering refined and effective treatments.
Methods of damaging cancer cells are of therapeutic interest. Here, the authors report on using gold nanoparticles as electron sinks with electroactive bacterial membranes to disrupt cancer cell redox balance, electron transfer induces oxidative stress and triggers cell death by apoptosis.
Journal Article
Radiocleavable rare-earth nanoactivators targeting over-expressed folate receptors induce mitochondrial dysfunction and remodel immune suppressive microenvironment in pancreatic cancer
Pancreatic cancer is a fatal cancer with poor prognosis and survival rate, often diagnosed usually in the advanced stage of disease. The conventional methods are usually considered for surgery or chemotherapy, and neo-adjuvant therapies have improved the survival rate in the patients. Folic acid plays a crucial role in the synthesis, metabolism, and repair of DNA; thereby, it is considered one of the biomolecules for cancer-targeted therapy for highly expressed receptors to overcome poor vasculature and dense tumor stroma, as in pancreatic cancer. This study strategizes for improving the therapeutic efficacy of pancreatic cancer via folate receptor-guided nanoparticles. The conjugation of folic acid (FA) to the LiYF
4
:Ce
3+
nanoparticles (SCNP-FA) with the photocleavage chemical molecule; firstly enters the cells through receptor-mediated endocytosis and then, releases FA intracellularly upon the trigger of radiation in a controlled manner. This nano-based approach induces ferroptosis to provoke immunogenic cell death (ICD) with higher generation of reactive oxygen species (ROS) and accumulation of lipid peroxides. It shows an abundant damage to the mitochondria and a decrease in mitochondrial membrane potential (MMP) upon treatment. This targeted therapy remodels the immunosuppressive tumor microenvironment and releases damage-associated molecular patterns (DAMPs) to initiate an immune response. These findings reveal the anti-tumor response with folate receptor-guided nanoparticles in pancreatic cancer.
Graphical abstract
Journal Article
Chromosomal instability induced by CRISPR/Cas9: implications for pancreatic cancer therapy
Clinical management of pancreatic cancer (PC) remains severely limited, primarily due to the complex tumor microenvironment. Emerging DNA damage–targeted strategies have demonstrated considerable therapeutic potential in PC. In this issue of the JCI , Teh et al. employed cancer-specific multitarget sgRNAs to induce DNA double-strand breaks (DSBs), resulting in lethal effects in PC cells. Integrative bioinformatic and cytogenetic analyses revealed that CRISPR/Cas9-mediated DSBs provoked persistent chromosomal instability, ultimately leading to chromosome catastrophe and cell death. Compared with equivalent radiation-induced DSBs, these sgRNAs exhibited superior cytotoxicity and were able to eliminate cells resistant to a specific sgRNA via subsequent targeting at distinct genomic sites, highlighting a promising and innovative precision therapeutic approach for clinical treatment of PC.
Journal Article
Wild-Type p53 Protein Enhances APR-246-Induced Cytotoxicity in Acute Myeloid Leukemia and Normal Hematopoietic Stem/Progenitor Cells
APR-246 (Eprenetapopt) is a small-molecule drug that restores the activity of dysfunctional p53 proteins caused by missense mutations that affect the DNA-binding domain. However, recent studies suggest that APR-246 can also induce cell death in cancer cells that carry wild-type (WT)
Here, we aimed to determine the impact of APR-246 on the survival of acute myeloid leukemia (AML) cells using isogenic Molm13 cells that harbor WT
, a missense mutation of
, or a biallelic deletion of
(
). Our results showed that Molm13
cells were significantly more resistant to APR-246-induced cell death compared with their Molm13
mutant and Molm13
counterparts. In addition, knockdown of
significantly reduced cytotoxicity induced by APR-246 in two
WT AML cell lines (MV4-11 and OCI-AML2). Moreover, APR-246 markedly decreased the clonogenicity of
WT hematopoietic stem/progenitor cells (HSPCs) isolated from humans and mice. In contrast, biallelic loss of
, but not
missense mutation, significantly increased the resistance of mouse HSPCs to APR-246. Mechanistically, the loss of functional p53 proteins in Molm13 and MV4-11 cells decreased intrinsic apoptosis and impaired the production of cellular reactive oxygen species (ROS) induced by APR-246. Together, our results indicate that, in at least a subset of AML cell lines and normal HSPCs, APR-246-induced ROS production and cytotoxicity are enhanced in the presence of WT p53 proteins.
Journal Article
TYRO3 induces anti–PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis
Immune checkpoint blockade therapy has demonstrated promising clinical outcomes for multiple cancer types. However, the emergence of resistance as well as inadequate biomarkers for patient stratification have largely limited the clinical benefits. Here, we showed that tumors with high TYRO3 expression exhibited anti-programmed cell death protein 1/programmed death ligand 1 (anti-PD-1/PD-L1) resistance in a syngeneic mouse model and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, TYRO3 inhibited tumor cell ferroptosis triggered by anti-PD-1/PD-L1 and facilitated the development of a protumor microenvironment by reducing the M1/M2 macrophage ratio, resulting in resistance to anti-PD-1/PD-L1 therapy. Inhibition of TYRO3 promoted tumor ferroptosis and sensitized resistant tumors to anti-PD-1 therapy. Collectively, our findings suggest that TYRO3 could serve as a predictive biomarker for patient selection and a promising therapeutic target to overcome anti-PD-1/PD-L1 resistance.
Journal Article
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial–mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal–epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
PD-L1 accumulates on cancer stem cells and favours immune evasion but the mechanism underlying this accumulation are unknown. Here the authors show that epithelial-mesenchymal transition induces glycosylation and stabilisation of PD-L1; antagonising this process renders cancer cells sensitive to anti-Tim3-therapy.
Journal Article