Open AccessCytosolic delivery of membrane-penetrating QDs into T cell lymphocytes: implications in immunotherapy and drug delivery
Author(s) -
Haoran Jing,
Marcell Pálmai,
Badeia Saed,
Anne George,
Preston T. Snee,
Ying Hu
Publication year - 2021
Publication title -
nanoscale
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.038
H-Index - 224
eISSN - 2040-3372
pISSN - 2040-3364
DOI - 10.1039/d0nr08362c
Subject(s) - intracellular , cytosol , drug delivery , immunotherapy , cell , cell membrane , membrane , biophysics , nanotechnology , chemistry , microbiology and biotechnology , materials science , medicine , immunology , immune system , biochemistry , biology , enzyme
We report single-particle characterization of membrane-penetrating semiconductor quantum dots (QDs) in T cell lymphocytes. We functionalized water-soluble CdSe/CdZnS QDs with a cell-penetrating peptide composed of an Asp-Ser-Ser (DSS) repeat sequence. DSS and peptide-free control QDs displayed concentration-dependent internalization. Intensity profiles from single-particle imaging revealed a propensity of DSS-QDs to maintain a monomeric state in the T cell cytosol, whereas control QDs formed pronounced clusters. Single-particle tracking showed a direct correlation between individual QD clusters' mobility and aggregation state. A significant portion of control QDs colocalized with an endosome marker inside the T cells, while the percentage of DSS-QDs colocalized dropped to 9%. Endocytosis inhibition abrogated the internalization of control QDs, while DSS-QD internalization only mildly decreased, suggesting an alternative cell-entry mechanism. Using 3D single-particle tracking, we captured the rapid membrane-penetrating activity of a DSS-QD. The ability to characterize membrane penetrating activities in live T cells creates inroads for the optimization of gene therapy and drug delivery through the use of novel nanomaterials.