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Cellular Internalization and Exiting Behavior of Zwitterionic 4-Armed Star-Shaped Polymers
Yuta Yoshizaki1, Tomohiro Konno1
1Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Molecules (Basel, Switzerland)
|June 10, 2023
Summary
Star-shaped phospholipid polymers (4armPMB) demonstrate rapid cellular uptake and release, similar to linear polymers, with no observed cytotoxicity. This architecture offers distinct cellular interaction dynamics for biomaterial applications.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Cell Biology
Background:
- Zwitterionic phospholipid polymers (PMB) are amphiphilic and biocompatible, known for cell membrane penetration.
- Conventional linear PMBs are synthesized via free radical polymerization.
- Branched polymer architectures, like star-shaped polymers, exhibit unique properties such as altered viscosity due to excluded volume effects.
Purpose of the Study:
- To synthesize a 4-armed star-shaped PMB (4armPMB) using atom transfer radical polymerization (ATRP).
- To compare the effects of branched (4armPMB) versus linear PMB architecture on cytotoxicity and cellular uptake.
- To investigate the cellular internalization and exiting behaviors influenced by polymer architecture.
Main Methods:
- Synthesis of 4-armed star-shaped PMB (4armPMB) and linear PMB using ATRP (a living radical polymerization technique).
- Verification of water solubility for both polymer types.
- Assessment of polymer aggregate behavior using pyrene fluorescence.
- Evaluation of cytotoxicity and cell membrane damage.
- Quantification of cellular uptake and back-diffusion rates.
Main Results:
- Both 4armPMB and linear PMB were successfully synthesized and confirmed to be water-soluble.
- Polymer architecture did not influence polymer aggregate behavior in solution.
- Neither 4armPMB nor linear PMB exhibited cytotoxicity or caused cell membrane damage.
- Both polymer architectures showed similar rates of cellular penetration after short incubation.
- 4armPMB demonstrated significantly faster back-diffusion from cells compared to linear PMB, indicating rapid cellular exiting.
Conclusions:
- The study successfully synthesized water-soluble 4-armed star-shaped and linear PMBs using ATRP.
- Both polymer architectures are cytocompatible and do not damage cell membranes.
- While cellular uptake rates are similar, the star-shaped architecture facilitates faster cellular exiting (back-diffusion) compared to the linear counterpart.
- The distinct cellular internalization and exiting dynamics of 4armPMB suggest potential for tailored biomaterial design.
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