Abstract
The effective escape of nanocarriers from endosomal compartments of the cell remains a major hurdle in nanomedicine. The endosomal escape of pH-responsive, self-assembled, dual component particles based on poly[2-(diethylamino)ethyl methacrylate)(PDEAEMA) and poly(ethylene glycol)-b-poly[2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) has been recently reported. Herein, we report that polymer molecular weight (Mn) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of Mn 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and co-assembled with PEG-b-PDEAEMA (16 kDa) via nanoprecipitation. All particles had similar size, displayed pH-responsive behaviour, and low toxicity regardless of molecular weight. Ovalbumin was loaded in the particles to demonstrate loading and release capabilities and as a marker to study internalization and endosomal escape. Association and endosomal escape was found to depend on molecular weight, with enhanced escape observed for high Mn PDEAEMA: 42% of cells with particle induced endosomal escape for 106 kDa nanoparticles, compared to minimal escape for 7 kDa particles. The results show that a simple variation in molecular weight can enhance the endosomal escape of polymeric carriers, and thus improve their effectiveness for intracellular delivery of therapeutics.
| Original language | English |
|---|---|
| Article number | 1600248 |
| Number of pages | 11 |
| Journal | Macromolecular Bioscience |
| Volume | 17 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Apr 2017 |
Keywords
- Endosomal escape
- Nanoparticles
- PH responsive
- Therapeutic delivery
Cite this
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Probing Endosomal Escape Using pHlexi Nanoparticles. / Kongkatigumjorn, Nachnicha; Cortez-Jugo, Christina; Czuba, Ewa; Wong, Adelene S M; Hodgetts, Rebecca Y.; Johnston, Angus P R; Such, Georgina K.
In: Macromolecular Bioscience, Vol. 17, No. 4, 1600248, 01.04.2017.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Probing Endosomal Escape Using pHlexi Nanoparticles
AU - Kongkatigumjorn, Nachnicha
AU - Cortez-Jugo, Christina
AU - Czuba, Ewa
AU - Wong, Adelene S M
AU - Hodgetts, Rebecca Y.
AU - Johnston, Angus P R
AU - Such, Georgina K.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - The effective escape of nanocarriers from endosomal compartments of the cell remains a major hurdle in nanomedicine. The endosomal escape of pH-responsive, self-assembled, dual component particles based on poly[2-(diethylamino)ethyl methacrylate)(PDEAEMA) and poly(ethylene glycol)-b-poly[2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) has been recently reported. Herein, we report that polymer molecular weight (Mn) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of Mn 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and co-assembled with PEG-b-PDEAEMA (16 kDa) via nanoprecipitation. All particles had similar size, displayed pH-responsive behaviour, and low toxicity regardless of molecular weight. Ovalbumin was loaded in the particles to demonstrate loading and release capabilities and as a marker to study internalization and endosomal escape. Association and endosomal escape was found to depend on molecular weight, with enhanced escape observed for high Mn PDEAEMA: 42% of cells with particle induced endosomal escape for 106 kDa nanoparticles, compared to minimal escape for 7 kDa particles. The results show that a simple variation in molecular weight can enhance the endosomal escape of polymeric carriers, and thus improve their effectiveness for intracellular delivery of therapeutics.
AB - The effective escape of nanocarriers from endosomal compartments of the cell remains a major hurdle in nanomedicine. The endosomal escape of pH-responsive, self-assembled, dual component particles based on poly[2-(diethylamino)ethyl methacrylate)(PDEAEMA) and poly(ethylene glycol)-b-poly[2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) has been recently reported. Herein, we report that polymer molecular weight (Mn) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of Mn 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and co-assembled with PEG-b-PDEAEMA (16 kDa) via nanoprecipitation. All particles had similar size, displayed pH-responsive behaviour, and low toxicity regardless of molecular weight. Ovalbumin was loaded in the particles to demonstrate loading and release capabilities and as a marker to study internalization and endosomal escape. Association and endosomal escape was found to depend on molecular weight, with enhanced escape observed for high Mn PDEAEMA: 42% of cells with particle induced endosomal escape for 106 kDa nanoparticles, compared to minimal escape for 7 kDa particles. The results show that a simple variation in molecular weight can enhance the endosomal escape of polymeric carriers, and thus improve their effectiveness for intracellular delivery of therapeutics.
KW - Endosomal escape
KW - Nanoparticles
KW - PH responsive
KW - Therapeutic delivery
UR - http://www.scopus.com/inward/record.url?scp=84995596341&partnerID=8YFLogxK
U2 - 10.1002/mabi.201600248
DO - 10.1002/mabi.201600248
M3 - Article
VL - 17
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
SN - 1616-5187
IS - 4
M1 - 1600248
ER -