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A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer

A key challenge in developing an anticancer aptamer is to efficiently determine the selectivity and specificity of the developed aptamer to the target ...

Deakin University

Triple-negative breast cancer (TNBC) has the worst prognosis among the subtypes of breast cancer, with no targeted therapy available. Immunotherapy targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) has resulted in some promising outcomes in cancer patients. The common treatments are monoclonal antibodies (mAbs). Despite novel methodologies in developing mAbs, there are several drawbacks with these medications. Immunological reactions, expensive and time-consuming production and requiring refrigeration are some of the challenging characteristics of mAbs that are addressed with using aptamers. Aptamers are nucleotide-based structures with high selectivity and specificity for target. Their small size helps aptamers penetrate the tissue better. In this review, we have discussed the nature of PD-1/PD-L1 interaction and summarised the available mAbs and aptamers specific for these two targets. This review highlights the role of aptamers as a future pathway for PD-1/PD-L1 modulation.

Future of PD-1/PD-L1 axis modulation for the treatment of triple-negative breast cancer.

The key challenges with the treatment of triple-negative breast cancer brain metastasis (TNBC-BM) are the lack of any targeted therapy and difficulties associated with drug delivery to the brain. These add to the high toxicity profile of existing treatments and the poor outcomes for patient. In this review, we introduce current drugs based on their molecular targets and look to improve brain drug delivery using more efficient and promising drug delivery systems. We describe ongoing clinical trials on druggable targets in TNBC-BM for a more targeted treatment and introduce the obstacles hindering drug delivery to the brain, bringing strategies and advancing knowledge for future steps in the treatment of patients with TNBC-BM.

Triple-negative breast cancer brain metastasis: An update on druggable targets, current clinical trials, and future treatment options.

The blood-brain barrier (BBB) is a strong barrier against the entrance of drugs, which has made brain cancer treatment a major challenge. We have previously shown that targeting transferrin receptors using aptamers increased brain drug delivery. To get a better understanding of this phenomenon, in the present article, a mathematical model based on the finite element method was developed accounting for the fluid flow and mass transport of the aptamer molecule inside an 8 µm capillary vessel across a 14 µm blood-brain barrier domain. The fluid flow and mass transport equations were coupled to calculate the blood velocity and aptamer concentration profiles across the BBB. It was identified that the thickness of the astrocyte and endothelial cell layers are key parameters affecting the concentration of the aptamer delivered to the last neuron dendrites in the BBB. The predicted efficacy of the drug delivery (C/C) of 10.9% to 13.8% was calculated at a porosity of 0.5 to 0.9, respectively, at a blood velocity of 0.38 mm/s, which was independent of the inlet concentration of the aptamer. This low efficacy was attributed to the mass transfer resistance across endothelial cells, astrocyte and pericyte layers, which decreased the concentration by 6.7%. It was also identified that the main mechanism of drug delivery is switched from convective mass transport in the capillary layer (with Peclet number > 50) to mixed convection mass transport (1 < Peclet number < 5) in the porous layers and to diffusion only once aptamer reached the brain parenchyma (Peclet number < 1).

Maryam Nakhjavani

School of Medicine,
Institute for Mental and Physical Health and Clinical Translation,
Institute for Mental and Physical Health and Clinical Translation, School of Medicine

Deakin University

A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer

Maryam Nakhjavani

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Medicine,Institute for Mental and Physical Health and Clinical Translation,Institute for Mental and Physical Health and Clinical Translation, School of Medicine

Deakin University

A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer

School of Medicine,
Institute for Mental and Physical Health and Clinical Translation,
Institute for Mental and Physical Health and Clinical Translation, School of Medicine