Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles.

Nanoscale

Laboratory of NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv 69978, Israel.

Published: April 2014

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.

Download full-text PDF

Source
http://dx.doi.org/10.1039/c3nr06102gDOI Listing

Publication Analysis

Top Keywords

tumor targeting
4
targeting profiling
4
profiling hyaluronan-coated
4
hyaluronan-coated lipid
4
lipid based-nanoparticles
4
based-nanoparticles hyaluronan
4
hyaluronan naturally
4
naturally occurring
4
occurring high
4
high hmw
4

Similar Publications

Glycobiology of psoriasis: A review.

J Autoimmun

January 2025

Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, No.38, Xueyuan Road, Haidian, Beijing, 100191, China. Electronic address:

Psoriasis is a chronic inflammatory skin disease with etiologies related to genetics, immunity, and the environment. It is characterized by excessive proliferation of keratinocytes and infiltration of inflammatory immune cells. Glycosylation is a post-translational modification of proteins that plays important roles in cell adhesion, signal transduction, and immune cell activation.

View Article and Find Full Text PDF

Epidermal growth factor receptor (EGFR) plays an important role in the regulation of cell proliferation and migration [1]. It forms a homodimer or heterodimer with other ErbB receptor family members to activate downstream signaling. Emerging evidence indicates that the EGFR activity and downstream signaling are regulated by other proteins except its family members during tumorigenesis.

View Article and Find Full Text PDF

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models.

View Article and Find Full Text PDF

The optimal method for three-dimensional thermal imaging within cells involves collecting intracellular temperature responses while simultaneously obtaining corresponding 3D positional information. Current temperature measurement techniques based on the photothermal properties of quantum dots face several limitations, including high cytotoxicity and low fluorescence quantum yields. These issues affect the normal metabolic processes of tumor cells.

View Article and Find Full Text PDF

How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm.

Blood

January 2025

Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.

Over the last decade significant advances have been made by honing in on the diagnostic evaluation and the significance of molecular profiles in patients with systemic mastocytosis (SM), non-advanced and advanced.This is reflected in the 2022 iterations of the World Health Organization Edition 5 and International Consensus Criteria classifications.The impact of targeted KIT inhibitor therapies on patients treated within global trials has demonstrated significant improvements in the prognosis and overall survival for patients, leading to a change the treatment paradigm.

View Article and Find Full Text PDF

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!