Boosting Oxidative Stress with Hydroxyethyl Starch Smart Nanomedicines to Eliminate Cancer Stem Cells

Accounts of Materials Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

ConspectusThe significance of cancer stem cells (CSCs), a rare population in tumor tissues, biology and the treatment solid malignancies has been widely appreciated for more than two decades. Due to peculiar self-renewal capability, even one single cell can grow into bulk mass. For this reason, CSCs have long blamed as major culprit initiation, progression, resistance, metastasis, recurrence. Therefore, it postulated that targeting could provide tremendous clinical benefits patients with tumors. Accumulating studies corroborated maintained tight regulation redox homeostasis fate was extremely sensitive elevated oxidative stress. Accordingly, plethora therapeutic drugs generate reactive oxygen species (ROS) leveraged target CSCs. Nonetheless, few or formulations are capable elevating stress achieved success eliminating thus far.Hydroxyethyl starch (HES) utilized plasma volume expander settings 50 years. Owing its merits excellent biocompatibility biodegradability, good water solubility manufacture practice, abundant hydroxy groups easy chemical modifications, HES attracted great attention tumor-targeted drug delivery. Specifically, nanoparticle stabilizer, nanocarrier conjugate chemotherapeutic by stimuli-responsive linkers, hydrophilic polymer link hydrophobic polymers form self-assembled nanoparticles. In Account, we summarize smart nanomedicines, developed our group during past five years, boost CSC elimination. According their effects on homeostasis, categorize these nanomedicines three classes. The first ones excessive ROS, means mitochondria-targeted photodynamic therapy (Mito-PDT), cuproptosis, ferroptosis. second own capability counteract endogenous reducing substances via inhibiting glutaminolysis depleting glutathione (GSH). third types simultaneously amplify ROS generation suppress antioxidant agents through combination strategies Mito-PDT plus inhibition, dynamic (CDT) GSH depletion, CDT depletion well inhibition. These rationally designed not only vitro but also eliminate numerous tumor-bearing mice models vivo, giving novel insights anti-CSC therapy. As is used clinic, hold significant potential translation.

Language: Английский

A potent nano-strategy for dual energy deprivation to inhibit pancreatic cancer progression

Nano Today, Journal Year: 2024, Volume and Issue: 59, P. 102528 - 102528

Published: Oct. 24, 2024

Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential found that methionine enhances mRNA methylation reduced the activation Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse models, single-cell demonstrated high levels elevate expression m 6 A reader YTHDF1, promoting degradation RIG-I, thereby inhibiting RIG-I/MAVS-mediated IFN-I reducing efficacy immunotherapy. Additionally, immunoprecipitation mass spectrometry revealed YTHDF1 binds to eukaryotic translation initiation factor eIF5B, which acts PD-L1 enhance its promote immune evasion. By intravesical administration oncolytic bacteria VNP20009, effectively depleted locally, significantly prolonging survival enhancing cell infiltration differentiation within tumors. Multiplex immunofluorescence assays cancer patients confirmed our findings. Our research elucidates two mechanisms by inhibits proposes a targeted depletion strategy advances while minimizing nutritional patients.

Language: Английский