Hyaluronic acid immobilized polyacrylamide nanoparticle sensors for CD44 receptor targeting and pH measurement in cells.

Our ability to design receptor-targeted nanocarriers aimed at drug release after endocytosis is limited by the current knowledge of intracellular nanoparticle (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting of cell surface receptors changes the intracellular fate of NPs; i.e.

The possible "proton sponge " effect of polyethylenimine (PEI) does not include change in lysosomal pH.

Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The "proton sponge " hypothesis remains the most generally accepted mechanism, although it is heavily debated.

Evaluating nanoparticle sensor design for intracellular pH measurements.

Particle-based nanosensors have over the past decade been designed for optical fluorescent-based ratiometric measurements of pH in living cells. However, quantitative and time-resolved intracellular measurements of pH in endosomes and lysosomes using particle nanosensors are challenging, and there is a need to improve measurement methodology. In the present paper, we have successfully carried out time-resolved pH measurements in endosomes and lyosomes in living cells using nanoparticle sensors and show the importance of sensor choice for successful quantification.

Polymeric nanosensors for measuring the full dynamic pH range of endosomes and lysosomes in mammalian cells.

Polymer nanoparticle sensors have been constructed for studying pH in the endocytic pathway in mammalian cells. The pH sensors for fluorescence ratiometric measurements were prepared using inverse microemulsion polymerization with rhodamine as reference fluorophor and fluorescein and oregon green as pH sensitive dyes, which gave a dynamic pH measurement range from 4.1-7.

Breast cancer cells can switch between estrogen receptor alpha and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance.

The majority of breast cancers are estrogen responsive, but upon progression of disease other growth promoting pathways are activated, e.g., the ErbB receptor system.

Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant.

Seven fulvestrant resistant cell lines derived from the estrogen receptor alpha positive MCF-7 human breast cancer cell line were used to investigate the importance of epidermal growth factor receptor (ErbB1-4) signaling. We found an increase in mRNA expression of EGFR and the ErbB3/ErbB4 ligand heregulin2 (hrg2) and a decrease of ErbB4 in all resistant cell lines. Western analyses confirmed the upregulation of EGFR and hrg2 and the downregulation of ErbB4.