The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/smll.202311507 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.
Nutrients
December 2024
Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Unidades Clínicas de Neurología y Salud Mental, 29010 Málaga, Spain.
Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.
View Article and Find Full Text PDFRecent advances and therapeutic applications of PPARγ-targeted ligands based on the inhibition mechanism of Ser273 phosphorylation.
Metabolism
December 2024
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation & Molecular Target and Clinical Pharmacology, the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address:
PPARγ functions as a master ligand-dependent transcription factor that regulates the expressions of a variety of key genes related to metabolic homeostasis and inflammatory immunity. It has been recognized as a popular and druggable target in modern drug discovery. Similar to other nuclear receptors, PPARγ is a phosphoprotein, and its biological functions are regulated by phosphorylation, especially at Ser273 site which is mediated by CDK5 or ERK.
View Article and Find Full Text PDFRoscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.
Int J Mol Sci
November 2024
Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Article Synopsis
- * Research has focused on post-translational modifications of the HTT protein, with findings showing that certain modifications can reduce the toxicity of the mutant protein in cell and animal models.
- * A study identified cyclin-dependent kinases (CDKs) that influence the phosphorylation of specific serine sites on HTT, and the CDK inhibitor roscovitine demonstrated protective effects against mutant HTT toxicity in HD mice, highlighting its potential as a pre-clinical therapeutic.
Identification and characterization of a surfactin from Pseudomonas gessardii: A symbiotic bacterium with potent anticancer activity.
Biochem Biophys Res Commun
December 2024
Department of Marine BioScience, College of Life Science, Gangneung-Wonju National University, Gangwon-do, 25457, Republic of Korea. Electronic address:
Prasiola japonica, traditionally used as food and folk medicine in South Korea, exerts pharmacological properties, including antioxidant, anti-inflammatory, antidiabetic, and anticancer effects. In this study, we explored symbiotic microbes associated with P. japonica and identified Pseudomonas gessardii as a nonpathogenic symbiotic bacterium through 16 S rDNA sequencing.
View Article and Find Full Text PDFPI3K/Akt inhibition promotes AR activity and prostate cancer cell proliferation through p35-CDK5 modulation.
Biochim Biophys Acta Mol Basis Dis
February 2025
Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan. Electronic address:
Article Synopsis
- Aberrant activation of the PI3K/Akt pathway is associated with the severity of prostate cancer (PCa), while the androgen receptor (AR) plays a vital role in the early stages of PCa development.
- A study found that p35-CDK5 acts as a mediator between PI3K/Akt and AR, promoting PCa cell growth and stability of the androgen receptor, particularly when the PI3K/Akt signaling is inhibited.
- Inhibiting PI3K/Akt not only increases p35 expression and enhances AR activation in PCa cells but also suggests that p35-CDK5 is essential for cell survival when PI3K/Akt activity is blocked.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!