Unlabelled: Exosomes have recently come into focus as "natural nanoparticles" for use as drug delivery vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we developed different methods of loading exosomes released by macrophages with PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our studies demonstrated a nearly complete co-localization of airway-delivered exosomes with cancer cells in a model of murine Lewis lung carcinoma pulmonary metastases, and a potent anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers.
From The Clinical Editor: Exosomes are membrane-derived natural vesicles of ~40 - 200 nm size. They have been under extensive research as novel drug delivery vehicles. In this article, the authors developed exosome-based system to carry formulation of PTX and showed efficacy in the treatment of multi-drug resistant cancer cells. This novel system may be further developed to carry other chemotherapeutic agents in the future.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809755 | PMC |
| http://dx.doi.org/10.1016/j.nano.2015.10.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An updated systematic review about various effects of microplastics on cancer: A pharmacological and in-silico based analysis.
Mol Aspects Med
January 2025
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Epidemiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan; Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. Electronic address:
Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis.
View Article and Find Full Text PDFCancer-Associated Fibroblast-Secreted Exosomes Regulate Macrophage Polarization in Pancreatic Cancer via the NOD1 Pathway.
J Biochem Mol Toxicol
January 2025
Department of Pathology and Pathophysiology, School of Medicine, Jinan University, Guangzhou, China.
Metastasis is a major cause of poor prognosis of pancreatic cancer. Exosomes (Exos) regulate cancer progression by modulating macrophage polarization. This study aimed to investigate the effects of cancer-associated fibroblast (CAF)-released Exos on macrophage polarization in pancreatic cancer and the molecular mechanisms.
View Article and Find Full Text PDFSLC7A5 is required for cancer cell growth under arginine-limited conditions.
Cell Rep
January 2025
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter.
View Article and Find Full Text PDFA non-canonical role for the tyrosyl tRNA synthetase: YARS regulates senescence induction and escape and controls the transcription of LIN9.
FEBS J
January 2025
Université d'Angers, Inserm, CNRS, CRCI2NA, ICO, Angers, France.
Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized.
View Article and Find Full Text PDFRef-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.
Angiogenesis
January 2025
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).
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!