Nanoparticle Surface Coupling to T Cells via CD45
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for coupling nanostructures to carrier cells, such as T cells, often result in internalization due to receptor-mediated endocytosis, limiting their use for targeted drug delivery and immunotherapy.
Innovation Solution
Surface-modifying nanostructures with ligands that bind to cell surface receptors like CD45, combined with the use of polycations, to stabilize the coupling of nanostructures to carrier cells and prevent internalization, allowing for efficient extracellular drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nanostructures are coupled to T cell surface using conventional methods, then coupling is achieved, but internalization occurs through receptor-mediated endocytosis
Solution Approach 1:
The patent uses CD45 receptor as an intermediary molecule that mediates the coupling between nanostructures and T cells. By targeting CD45, which has prolonged surface residence time, the nanostructures are stably coupled to the cell surface without triggering internalization, thus resolving the contradiction between coupling stability and cell surface retention
Solution Approach 2:
The patent changes the binding parameter by selecting CD45-specific ligands instead of conventional T cell receptors. This parameter change in receptor specificity transforms the internalization-prone coupling into a stable surface-retained coupling, achieving both reliable coupling and sustained cell surface retention
2Productivity
If polycation is added to nanostructure surface, then coupling efficiency increases to 89.6%, but cellular toxicity is expected
Solution Approach 1:
The patent applies polycation coating locally and selectively to the nanostructure surface rather than uniformly to all surfaces. This localized application ensures high coupling efficiency at the interaction interface while minimizing overall toxicity exposure to cells, resolving the contradiction between productivity and harmful factors
Solution Approach 2:
The patent uses a disposable polycation coating layer on the nanostructure surface that performs its function of enhancing coupling efficiency and then can be shed or degraded. This temporary, sacrificial coating achieves high productivity during the coupling process while limiting long-term toxic exposure to cellular systems
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach achieves a high coupling efficiency of up to 89.6% and maintains nanostructures on the cell surface, enabling stable and targeted delivery of therapeutic agents with reduced toxicity, as demonstrated by the use of IL-15Sa protein nanogels in adoptive cell therapy.
Implementation Method 1
nanostructures surface-modified with (e.g., conjugated to), for example, a ligand that binds to CD45 (e.g., an anti-CD45 antibody) are maintained at the surface of T cells expressing CD45
Implementation Method 2
a coupling efficiency of, for example, 89.6% can be achieved when adding a polycation (e.g., poly-L-lysine) to the surface of a nanostructure prior to performing a coupling reaction with a carrier cell
Data Source
AI summary
The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.