Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Polymers 2011, 3(2), 693-718; doi:10.3390/polym3020693
Article

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

1,†
, 1,2,†
, 1
, 1,*  and 1
Received: 22 February 2011; Accepted: 25 March 2011 / Published: 28 March 2011
(This article belongs to the Special Issue Biofunctional Polymers for Medical Applications)
View Full-Text   |   Download PDF [1939 KB, updated 29 March 2011; original version uploaded 28 March 2011]
Abstract: The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl amino)ethyl methacrylate) (pDMAEMA) and poly(2-hydroxyethyl methacrylate) (pHEMA). Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl amino)ethyl methacrylate-block-poly(2-hydroxyl methacrylate) (pDMAEMA-block-pHEMA) copolymers was synthesized via RAFT (reversible addition-fragmentation chain transfer) polymerization in a molecular weight (Mw) range of 17–35.7 kDa and analyzed using 1H and 13C NMR (nuclear magnetic resonance), ATR (attenuated total reflectance), GPC (gel permeation chromatography) and DSC (differential scanning calorimetry). Copolymers possessing short pDMAEMA-polycation chains were 1.4–9.7 times less toxic in vitro than polyethylenimine (PEI) 25 kDa, and complexed DNA into polyplexes of 100–170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15–30 mV). In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA115 (18.3 kDa) self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa) to pDMAEMA115 increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection efficacy and kinetics of low molecular weight pDMAEMA-block-pHEMA are subject of ongoing studies.
Keywords: low molecular pDMAEMA; linear pDMAEMA-block-pHEMA diblock copolymers; RAFT-polymerization; poly(2-(dimethyl amino) ethyl methacrylate); poly(2-hydroxyethylmethacrylate); physico-chemical characterization; in vitro pDNA transfection; cytotoxicity low molecular pDMAEMA; linear pDMAEMA-block-pHEMA diblock copolymers; RAFT-polymerization; poly(2-(dimethyl amino) ethyl methacrylate); poly(2-hydroxyethylmethacrylate); physico-chemical characterization; in vitro pDNA transfection; cytotoxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Samsonova, O.; Pfeiffer, C.; Hellmund, M.; Merkel, O.M.; Kissel, T. Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents? Polymers 2011, 3, 693-718.

AMA Style

Samsonova O, Pfeiffer C, Hellmund M, Merkel OM, Kissel T. Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents? Polymers. 2011; 3(2):693-718.

Chicago/Turabian Style

Samsonova, Olga; Pfeiffer, Christian; Hellmund, Markus; Merkel, Olivia M.; Kissel, Thomas. 2011. "Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?" Polymers 3, no. 2: 693-718.


Polymers EISSN 2073-4360 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert