Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s
The delivery of therapeutic agents into target cells is a challenging task. Cell penetration and intracellular targeting were recently addressed with biodegradable cell-penetrating poly(disulfide)s (CPDs). Cellular localization is determined by the length of these polymers, emphasizing the significa...
| Main Authors: | , , , , , , |
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| 格式: | Journal article |
| 语言: | English |
| 出版: |
American Chemical Society
2019
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| _version_ | 1826302899181846528 |
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| author | Pulcu, G Galenkamp, N Qing, Y Gasparini, G Mikhailova, E Matile, S Bayley, H |
| author_facet | Pulcu, G Galenkamp, N Qing, Y Gasparini, G Mikhailova, E Matile, S Bayley, H |
| author_sort | Pulcu, G |
| collection | OXFORD |
| description | The delivery of therapeutic agents into target cells is a challenging task. Cell penetration and intracellular targeting were recently addressed with biodegradable cell-penetrating poly(disulfide)s (CPDs). Cellular localization is determined by the length of these polymers, emphasizing the significance of initial chain length and the kinetics of intracellular depolymerization for targeted delivery. In the present study, the kinetics of CPD polymer growth and degradation were monitored in a single-molecule nanoreactor. The chain lengths achievable under synthetic conditions with high concentrations of dithiolanes were then predicted by using the rate constants. For example, CPDs comprising 40 units are generated in 1 s at pH 7.4 and 0.3 s at pH 8.4 at dithiolane concentrations of 200 mM. The rate constants for degradation suggest that the main depolymerization pathway in the cell is by monomer removal by self-cyclization, rather than by intrachain cleavage by endogenous thiols. |
| first_indexed | 2024-03-07T05:54:26Z |
| format | Journal article |
| id | oxford-uuid:ea049c02-9192-41f3-8465-17c1c5c8afe8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:54:26Z |
| publishDate | 2019 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:ea049c02-9192-41f3-8465-17c1c5c8afe82022-03-27T10:58:42ZSingle-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)sJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ea049c02-9192-41f3-8465-17c1c5c8afe8EnglishSymplectic Elements at OxfordAmerican Chemical Society2019Pulcu, GGalenkamp, NQing, YGasparini, GMikhailova, EMatile, SBayley, HThe delivery of therapeutic agents into target cells is a challenging task. Cell penetration and intracellular targeting were recently addressed with biodegradable cell-penetrating poly(disulfide)s (CPDs). Cellular localization is determined by the length of these polymers, emphasizing the significance of initial chain length and the kinetics of intracellular depolymerization for targeted delivery. In the present study, the kinetics of CPD polymer growth and degradation were monitored in a single-molecule nanoreactor. The chain lengths achievable under synthetic conditions with high concentrations of dithiolanes were then predicted by using the rate constants. For example, CPDs comprising 40 units are generated in 1 s at pH 7.4 and 0.3 s at pH 8.4 at dithiolane concentrations of 200 mM. The rate constants for degradation suggest that the main depolymerization pathway in the cell is by monomer removal by self-cyclization, rather than by intrachain cleavage by endogenous thiols. |
| spellingShingle | Pulcu, G Galenkamp, N Qing, Y Gasparini, G Mikhailova, E Matile, S Bayley, H Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title | Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title_full | Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title_fullStr | Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title_full_unstemmed | Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title_short | Single-molecule kinetics of growth and degradation of cell-penetrating poly(disulfide)s |
| title_sort | single molecule kinetics of growth and degradation of cell penetrating poly disulfide s |
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