Nanobots the Artificial Blood: The Potential of Mechanical Red Cells and Platelets

HBOCs from expired human blood or fresh bovine blood have to undergo numerous modifications to make them safe and effective oxygen carriers. The RBCs are first lysed to release their hemoglobin, and then the stroma is removed by a variety of methods, including centrifugation, filtration and chemical extraction. The stroma-free hemoglobin is then purified and undergoes modifications to cross-link, polymerize or conjugate it to other compounds. Without these modifications, the oxygen affinity of the stroma-free hemoglobin is too great to facilitate oxygen release in the tissues. Also, when it is outside the RBC, hemoglobin rapidly dissociates into 32 kDa αβ dimers and 16 kDa α or β monomers, both of which are rapidly filtered in the kidney and can precipitate in the loop of Henle, resulting in severe renal toxicity. The dimer haem iron is oxidized more easily than in the tetramer, leading to molecules unable to bind oxygen. Moreover, the formation of ferric ions triggers a cascade of reactions that generate reactive oxygen species and reactive nitrogen species, the molecular basis of oxidative damage.

nanobots the artificial blood pdf 14

Download File: https://tinourl.com/2vGBbP

[A] Arterial and venous circulation pathways in the body that carries RBCs, WBCs andplatelets for respective biological functions; [B] Representative histology stain of bloodsmear showing RBC, WBC and platelet; [C] Schematic cartoon and representative SEM image ofRBC; [D] Schematic cartoon and representative SEM image of WBC; [E] Schematic cartoon andrepresentative SEM images of resting and active platelets.

[A]-[E] Chemical structure of various perfluorocarbon (PFC) compounds that have beenstudied for oxygen carrying applications; [F] Oxygen binding curves of whole blood andHBOC systems (cooperative sigmoid binding characteristics) compared with tat PFC-basedoxygen carriers (linear binding characteristics).

Process scheme and representative particle images (fluorescence or SEM) for [A] thePRINT technology and [B] the template-mediated thermostretching and layer-by-layerassembly based technology to produce micro- and nanoparticles that mimic the size andshape of blood cells (e.g. RBCs and platelets).

Since 2017, six CAR T-cell therapies have been approved by the Food and Drug Administration (FDA). All are approved for the treatment of blood cancers, including lymphomas, some forms of leukemia, and, most recently, multiple myeloma.

As part of their immune-related duties, T cells release cytokines, chemical messengers that help stimulate and direct the immune response. In the case of CRS, the infused T cells flood the bloodstream with cytokines, causing serious side effects, including dangerously high fevers and precipitous drops in blood pressure. In some cases, severe CRS can be fatal.

Although CD19 and BCMA are the only antigens for which there are FDA-approved CAR T-cell therapies, CAR T-cell therapies have been developed that target other antigens commonly found in blood cancers, including therapies that target multiple antigens at one time.

Nanoparticles can be used in the efficient delivery of drugs to diseased cells when treating cancer or other diseases. Nanoparticles can also be used in the diagnosis of life-threatening blood clots which often remain unexposed until they break down in the body.

Recently researchers at MIT have created synthetic nanoparticles which allow a better detection of blood clots and cancer. The researchers coated nanoparticles with a number of short protein fragments known as peptides.

Scientists have long been working on biomarkers which can detect cancer and other diseases but this has proved a challenging task. The recent discovery of synthetic biomarkers has been remarkable in the early diagnosis of cancer and the monitoring of tiny blood clots in the body.

Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells. CAR T-cell therapy is also sometimes talked about as a type of cell-based gene therapy, because it involves altering the genes inside T cells to help them attack the cancer.

In CAR T-cell therapies, T cells are taken from the patient's blood and are changed in the lab by adding a gene for a receptor (called a chimeric antigen receptor or CAR), which helps the T cells attach to a specific cancer cell antigen. The CAR T cells are then given back to the patient.

The patient will need to stay seated or lying down for 2 to 3 hours during the procedure. Sometimes blood calcium levels can drop during leukapheresis, which can cause numbness and tingling or muscle spasms. This can be treated by replacing the calcium, which may be given by mouth or through an IV.

Cytokine release syndrome (CRS): As CAR T cells multiply, they can release large amounts of chemicals called cytokines into the blood, which can ramp up the immune system. Serious side effects from this release can include:

The International Diabetes Closed-Loop (iDCL) Study involves five separate artificial pancreas clinical protocols implemented by 10 research centers in the United States and Europe. This six-month study was the third phase in a series of trials. It was conducted with participants living their usual day-to-day lives, so the researchers could best understand how the system works in typical daily routines.

This iDCL protocol enrolled 168 participants age 14 or older with type 1 diabetes. They were randomly assigned to use either the artificial pancreas system called Control-IQ or sensor-augmented pump (SAP) therapy with a CGM and insulin pump that did not automatically adjust insulin throughout the day. Participants had contact with study staff every two to four weeks to download and review device data. No remote monitoring of the systems was done, so that the study would reflect real-world use.

The researchers found that users of the artificial pancreas system significantly increased the amount of time with their blood glucose levels in the target range of 70 to 180 mg/dL by an average of 2.6 hours per day since beginning the trial, while the time in range in the SAP group remained unchanged over six months. Artificial pancreas users also showed improvements in time spent with high and low blood glucose, hemoglobin A1c, and other measurements related to diabetes control compared to the SAP group. High adherence to device use in both groups and 100% participant retention were important strengths of the study. During the study, no severe hypoglycemia events occurred in either group. Diabetic ketoacidosis occurred in one participant in the artificial pancreas group due to a problem with equipment that delivers insulin from the pump.

The iDCL Study is one of four major research efforts funded by NIDDK through the Special Statutory Funding Program for Type 1 Diabetes to test and refine advanced artificial pancreas systems. The studies, with additional results forthcoming, are looking at factors including safety, efficacy, user-friendliness, physical and emotional health of participants, and cost.

CTCs are epithelial cancer cells that have the ability to move, migrate and invade blood vessels after epithelial-mesenchymal transition (EMT) and are considered the main cause of tumor metastasis in vivo [9, 10]. Upon reaching an appropriate niche, CTCs undergo mesenchymal-epithelial transition (MET), reacquire stem cell properties and form a new metastatic site [11]. Unlike other cancer biomarkers, CTCs are live tumor cells that carry molecular and biological information about the tumor as a whole, support single cell analysis, and directly reflect the ongoing changes in tumors at all stages [12].

The roles of CTC in tumor metastasis and the current applications of CTC technologies. Tumor cells translocate from the primary tumor and invade into the bloodstream to become CTCs. Most CTCs affected by microenvironment and undergo apoptosis. Some CTCs undergo phenotypic changes after EMT and finally forming metastases. CTCs are preliminary enriched from whole blood sample via different enrichment techniques. Different detection technologies such as CTC count, phenotypic analysis and single cell analysis can help with early detection, prognostication, chemotherapy, target therapy of patients

Strategies for CTC enrichment. a A fiber mat of electrospun nylon-6/PEO fibre for CTCs capture; b A ZnO nanowire coated polydimethylsiloxane pillar substrate with a gear structure; c Tumor-targeting molecule folic acid (FA) and magnetic nanoparticles (MNPs) coated engineered red blood cells (RBCs); d A microfluidic device integrated of dendrimer-mediated multivalent binding, a mixture of antibodies, and biomimetic cell rolling; e An ensemble-decision aliquot ranking (eDAR) microfluidic device using sequential sorting and flow stretching. a Copyright Springer Nature 2018. Reproduced with permission from reference [24]; b Copyright RSC Publishing 2020. Reproduced with permission from reference [25]; c Copyright RSC Publishing 2018. Reproduced with permission from reference [26]; d Copyright Elsevier 2020. Reproduced with permission from reference [40]; e Copyright American Chemical Society 2019. Reproduced with permission from reference [61]

Metastasis is the major challenge in cancer management. Many studies have suggested that primary tumor cells need to undergo EMT before invading blood vessels and gaining metastatic ability. These cells experience different degrees of EMT and gain several different subtypes, including the epithelial type, mesenchymal type or mixed type, and the expression of EpCAM on the surface of CTCs is downregulated to varying degrees, making it difficult for these heterogeneous cells to be enriched by EpCAM-dependent CTC capture technologies. These tumor cell subsets are of great significance for studying the mechanism of cancer transmission and metastasis. Therefore, researchers have improved many aspects of CTC capture techniques, such as antibodies, biological probes, and the source of blood samples. 2ff7e9595c