Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect. Using periplocymarin (PPM) as a target agent, we designed a novel redox-responsive prodrug conjugated with linoleic acid (PPM-ss-LA), which was capable of self-assembling independent of exogenous excipients. This prodrug could co-assemble with DSPE to form PEGylated prodrug nanoparticles (PPM-ss-LA/DSPE-NPs) with enhanced colloidal stability and blood circulation. Compared with free PPM, PPM-ss-LA/DSPE-NPs retained high anti-proliferative activity and showed increased cell uptake and therapeutic efficacy. Furthermore, the PPM-ss-LA/DSPE-NPs acquired a greatly enhancement of 50% lethal dose (LD) in mice and reduced system toxicity compared with the free drug. Overall, the on-demand release of nanoprodrug delivery system could improve the therapeutic window and anticancer efficacy of CGs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijpharm.2019.118980 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rare dual MYH9-ROS1 fusion variants in a patient with lung adenocarcinoma: A case report.
Medicine (Baltimore)
January 2025
Department of Respiratory and Critical Care Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, China.
Rationale: ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported.
View Article and Find Full Text PDFFocused ultrasound therapy as a strategy for improving glioma treatment.
J Neurosurg
January 2025
Departments of1Neurological Surgery and.
The infiltrative and diffuse nature of gliomas makes complete resection unfeasible. Unfortunately, regions of brain parenchyma with residual, infiltrative tumor are protected by the blood-brain barrier (BBB), making systemic chemotherapies, small-molecule inhibitors, and immunotherapies of limited efficacy. Low-frequency focused ultrasound (FUS) in combination with intravascular microbubbles can be used to disrupt the BBB transiently and selectively within the tumor and peritumoral region.
View Article and Find Full Text PDFMature chromatin packing domains persist after RAD21 depletion in 3D.
Sci Adv
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.
View Article and Find Full Text PDFLeveraging Structural and Computational Biology for Molecular Glue Discovery.
J Med Chem
January 2025
Experimental Drug Development Centre, Chromos, Agency for Science, Technology and Research, 10 Biopolis Road, #05-01, Singapore 138670.
The discovery of molecular glues has made significant strides, unlocking new avenues for targeted protein degradation as a therapeutic strategy, thereby expanding the scope of drug discovery into territories previously considered undruggable. Pioneering molecules like thalidomide and its derivatives have paved the way for the development of small molecules that can induce specific protein degradation by hijacking the cellular ubiquitin-proteasome system. Recent advancements have focused on expanding the range of E3 ligases and target proteins that can be modulated by molecular glues.
View Article and Find Full Text PDFMacromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.
Proc Natl Acad Sci U S A
January 2025
Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.
View Article and Find Full Text PDFWant 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!