Nanoparticle-Mediated Intracellular Protection of Natural Killer Cells Avoids Cryoinjury and Retains Potent Antitumor Functions.

The ability of natural killer (NK) cells to mediate potent antitumor immunity in clinical adoptive transfer arrangement depends, in large part, on their ability to maintain function following cytotoxic cryopreservation. To avoid potential systemic toxicity associated with NK cell infusion to the patient in the presence of dimethylsulfoxide (DMSO), interest in alternative cryoprotective agent (CPA) with improved safety profile has grown. 

Although the development of a variety of sugars, amino acids, polyols, and polyampholytes as cryoprotectant, their ability to promote the protection of intracellular cryodamage limited as they mostly act outside the cell. Although the shuttle intracellular cryoprotectant way there, high aversity NK cells for manipulation and freezing means that they are very understudied as a target for the development of new cryopreservation approach. Here, the first example of a platform that is safe and efficient for intracellular delivery of non-DMSO CPA presented to NK cells.

 Biocompatible chitosan-based nanoparticles engineered Western Blot to mediate efficient free DMSO cryopreservation of NK cells. NK cells are cryopreserved in this manner retains strong cytotoxic, degranulation, cytokine production and function against tumor targets. It is not only the first example provides nanoparticles for NK cells, but illustrate the clinical potential in manufacturing safer adoptive immunotherapies allogeneic "off the shelf."

Investigation ultrasound-mediated intracellular Ca2 + oscillations in HIT-T15 pancreatic β-Sel.

Glucose-stimulated insulin secretion (GSIS) of pancreatic β-cells, the increase in free cytosolic Ca2 + concentration via voltage-gated calcium channel (VGCCs) triggers exocytosis of insulin-containing granules. More recently, the line is mechanically induced insulin secretion was also reported, which take advantage of free cytosolic Ca2 + ion as a direct regulator of exocytosis. 

In this study, we aimed to investigate the intracellular Ca2 + responses in HIT-T15 line-cell β pancreas at low intensity pulsed ultrasound (LIPUS) stimulation and found that induces an ultrasound two different types of intracellular Ca2 + oscillations, Fab  fast-irregular and periodic slow, from another cell rest. Both Ca2 + pattern depending on the purinergic signaling is activated by the appearance of extracellular ATP or ADP concentration on ultrasound stimulation, which facilitates the release through hemichannels mechanosensitive the plasma membrane. 

Further study showed that two purinergic receptor subtypes, P2X and P2Y, working with a competitive manner depending on the level of glucose in the cell media. The findings can serve as an important foundation provides the underlying mechanisms for the development of a new therapeutic approach for diabetic condition with further validation.